The Diagnosis: Trigeminal Trophic Syndrome (Self-induced Trauma) 

The patient admitted to manipulation of the ala in response to persistent pain despite resolution of the herpes zoster, for which he recently had completed a course of oral acyclovir. A preliminary diagnosis of trigeminal trophic syndrome (TTS) was made, and a subsequent punch biopsy revealed no evidence of malignancy. Topical antibiotic prophylaxis was prescribed, and he was instructed to avoid manipulation of the affected area. Treatment was initiated in consultation with pain specialists, and over the following 3 years our patient experienced a waxing and waning course of persistent pain complicated by new scalp and oral ulcers as well as alar impetigo. His condition eventually stabilized with tolerable pain on oral gabapentin and doxepin cream 5% applied up to 4 times daily. The alar lesion healed following sufficient abstinence from manipulation, leaving a crescent-shaped rim defect.  

Trigeminal trophic syndrome classically is characterized by a triad of cutaneous anesthesia, paresthesia and/or pain, and ulceration secondary to pathology of trigeminal nerve sensory branches. Ulceration arises primarily through excoriation in response to paresthetic pruritus or pain. The differential diagnosis for TTS includes ulcerating cutaneous neoplasms (eg, basal cell carcinoma); mycobacterial, fungal, and viral infections (especially herpetic lesions); and cutaneous involvement of systemic vasculitides (eg, granulomatosis with polyangiitis).¹ Biopsy is necessary to exclude malignancy, and ulcers may be scraped for viral diagnosis. Complete blood cell count and serologic testing also may help to exclude immunodeficiencies or disorders. Apart from viral neuropathy, common etiologies of TTS include iatrogenic trigeminal injury (eg, in ablation treatment for trigeminal neuralgia) and stroke (eg, lateral medullary syndrome).  

The Diagnosis: Trigeminal Trophic Syndrome (Self-induced Trauma) 

The patient admitted to manipulation of the ala in response to persistent pain despite resolution of the herpes zoster, for which he recently had completed a course of oral acyclovir. A preliminary diagnosis of trigeminal trophic syndrome (TTS) was made, and a subsequent punch biopsy revealed no evidence of malignancy. Topical antibiotic prophylaxis was prescribed, and he was instructed to avoid manipulation of the affected area. Treatment was initiated in consultation with pain specialists, and over the following 3 years our patient experienced a waxing and waning course of persistent pain complicated by new scalp and oral ulcers as well as alar impetigo. His condition eventually stabilized with tolerable pain on oral gabapentin and doxepin cream 5% applied up to 4 times daily. The alar lesion healed following sufficient abstinence from manipulation, leaving a crescent-shaped rim defect.  

Trigeminal trophic syndrome classically is characterized by a triad of cutaneous anesthesia, paresthesia and/or pain, and ulceration secondary to pathology of trigeminal nerve sensory branches. Ulceration arises primarily through excoriation in response to paresthetic pruritus or pain. The differential diagnosis for TTS includes ulcerating cutaneous neoplasms (eg, basal cell carcinoma); mycobacterial, fungal, and viral infections (especially herpetic lesions); and cutaneous involvement of systemic vasculitides (eg, granulomatosis with polyangiitis).¹ Biopsy is necessary to exclude malignancy, and ulcers may be scraped for viral diagnosis. Complete blood cell count and serologic testing also may help to exclude immunodeficiencies or disorders. Apart from viral neuropathy, common etiologies of TTS include iatrogenic trigeminal injury (eg, in ablation treatment for trigeminal neuralgia) and stroke (eg, lateral medullary syndrome).  

The Diagnosis: Trigeminal Trophic Syndrome (Self-induced Trauma) 

The patient admitted to manipulation of the ala in response to persistent pain despite resolution of the herpes zoster, for which he recently had completed a course of oral acyclovir. A preliminary diagnosis of trigeminal trophic syndrome (TTS) was made, and a subsequent punch biopsy revealed no evidence of malignancy. Topical antibiotic prophylaxis was prescribed, and he was instructed to avoid manipulation of the affected area. Treatment was initiated in consultation with pain specialists, and over the following 3 years our patient experienced a waxing and waning course of persistent pain complicated by new scalp and oral ulcers as well as alar impetigo. His condition eventually stabilized with tolerable pain on oral gabapentin and doxepin cream 5% applied up to 4 times daily. The alar lesion healed following sufficient abstinence from manipulation, leaving a crescent-shaped rim defect.  

Trigeminal trophic syndrome classically is characterized by a triad of cutaneous anesthesia, paresthesia and/or pain, and ulceration secondary to pathology of trigeminal nerve sensory branches. Ulceration arises primarily through excoriation in response to paresthetic pruritus or pain. The differential diagnosis for TTS includes ulcerating cutaneous neoplasms (eg, basal cell carcinoma); mycobacterial, fungal, and viral infections (especially herpetic lesions); and cutaneous involvement of systemic vasculitides (eg, granulomatosis with polyangiitis).¹ Biopsy is necessary to exclude malignancy, and ulcers may be scraped for viral diagnosis. Complete blood cell count and serologic testing also may help to exclude immunodeficiencies or disorders. Apart from viral neuropathy, common etiologies of TTS include iatrogenic trigeminal injury (eg, in ablation treatment for trigeminal neuralgia) and stroke (eg, lateral medullary syndrome).  

A proposal to delay administration of the second dose of COVID-19 vaccines – suggested as a strategy to boost the number of people who get some degree of protection from a single immunization with the Pfizer/BioNTech or Moderna vaccines – is inciting a strong debate among clinicians and public health officials.

Proponents argue that getting some degree of protection to a greater number of Americans is worthwhile, particularly as case numbers and hospitalizations continue to rise and with the emergence of a more contagious variant.

Opponents raise concerns about diverting from the two-dose schedule evaluated in clinical trials, including a lack of data on long-term protection from a single dose. They also suggest a longer interval between dosing could increase resistance of SARS-CoV-2 virus.

It is time to consider delaying the second dose, Robert M. Wachter, MD, at the University of California San Francisco, and Ashish Jha, MD, MPH, at Brown University in Providence, R.I., wrote in an opinion piece in The Washington Post Jan. 3. 

The two experts state that supply constraints, distribution bottlenecks, and hundreds of thousands of new infections daily prompted them to change their stance on administering COVID-19 vaccines according to the two-dose clinical trial regimen. Furthermore, they cited a study in the New England Journal of Medicine that suggests 80%-90% efficacy for preventing SARS-CoV-2 infection following one dose of the Moderna vaccine. 

Not everyone agrees one dose is a good idea. “Clinical trials with specific schedules for vaccine dosing – that’s the whole basis of the scientific evidence,” Maria Elena Bottazzi, PhD, associate dean of the National School of Tropical Medicine at Baylor College of Medicine in Houston, said in an interview.

After one dose “the immune system is learning, but it’s not ideal. That’s why you need the second dose,” Dr. Bottazzi said. “I appreciate the urgency and the anxiety ... but the data support [that] clinical efficacy requires two doses.”

Another proposed strategy to extend the current supply of COVID-19 vaccines to more Americans involves splitting the current dosage of the Moderna vaccine in half. Officials in the United States and the United Kingdom are reportedly considering this approach. In the United States, the Food and Drug Administration would have to approve any dosing change.
 

Agreeing to disagree

Dr. Wachter shared a link to his opinion piece on Twitter, stating that “We both came to this view because of the slow rollout & the new variant. But it’s a tough call and reasonable people will disagree.”

As predicted, the tweet elicited a number of strong opinions.

“There are no correct answers but there’s data deficiency, plenty of fodder and need for healthy, intellectual debate. That wouldn’t be occurring if there was an ample supply of vaccines,” Eric Topol, MD, director of the Scripps Translational Science Institute and editor-in-chief of Medscape, tweeted on Jan. 3.

“If the problem were with the supply of the vaccine, one might make an argument for focusing on 1st dose. But the problem is in distribution of the vaccine & giving actual doses,” John Grohol, PsyD, tweeted.

“Right now we don’t have a supply issue, we have a distribution issue,” Angela Shen, ScD, MPH, a research scientist in the Vaccine Education Center at Children’s Hospital of Philadelphia, said in an interview. Emergency use authorization for the Johnson & Johnson and other COVID-19 vaccines in development could further boost available supplies, she added.

“The clinical trials studied two doses,” Dr. Shen said. “We don’t have data that one dose is going to have lasting protection.” 
 

Does new variant change equation?

Dr. Wachter and Dr. Jha, in their editorial, cited a quote from former boxing champion Mike Tyson: “Everybody has a plan until they’ve been punched in the mouth.” ‘Punches’ such as the new variant, the high number of cases and deaths in the United States, and other problems prompted them to advocate for the delayed dosing strategy.

“Appreciate the concern for the new variant – I think it’s worth noting that we’re punching ourselves in the mouth with the slow vaccine rollout, which is the first problem to solve,” Jake Quinton, MD, an internist at UCLA Health in Los Angeles, noted on Twitter.

 

Vaccine and public resistance raised

“I agree with the problem but not with the proposed solution, which is guesswork not based on data,” the Jan Grimm Lab at Memorial Sloan Kettering Cancer Center in New York responded to Dr. Wachter and Dr. Jha on Twitter. “There ARE data though that show that 1 shot alone did not elicit sufficient T-cell nor antibody response. This might also lead to mutations resistant to the vaccines. Dangerous!”

Other physicians took to Twitter to point out that changing the recommendations at this point could further erode public confidence in COVID-19 immunization. For example, Deirdre Habermehl, MD, wrote, “We’ve spent months telling the public the best route is to follow the science and now without data think a course correction based on a guesstimate is ok? Public confidence is low enough and the real issue is logistics at this point.”

Dr. Shen and Dr. Bottazzi have disclosed no relevant financial relationships.

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

A proposal to delay administration of the second dose of COVID-19 vaccines – suggested as a strategy to boost the number of people who get some degree of protection from a single immunization with the Pfizer/BioNTech or Moderna vaccines – is inciting a strong debate among clinicians and public health officials.

Proponents argue that getting some degree of protection to a greater number of Americans is worthwhile, particularly as case numbers and hospitalizations continue to rise and with the emergence of a more contagious variant.

Opponents raise concerns about diverting from the two-dose schedule evaluated in clinical trials, including a lack of data on long-term protection from a single dose. They also suggest a longer interval between dosing could increase resistance of SARS-CoV-2 virus.

It is time to consider delaying the second dose, Robert M. Wachter, MD, at the University of California San Francisco, and Ashish Jha, MD, MPH, at Brown University in Providence, R.I., wrote in an opinion piece in The Washington Post Jan. 3. 

The two experts state that supply constraints, distribution bottlenecks, and hundreds of thousands of new infections daily prompted them to change their stance on administering COVID-19 vaccines according to the two-dose clinical trial regimen. Furthermore, they cited a study in the New England Journal of Medicine that suggests 80%-90% efficacy for preventing SARS-CoV-2 infection following one dose of the Moderna vaccine. 

Not everyone agrees one dose is a good idea. “Clinical trials with specific schedules for vaccine dosing – that’s the whole basis of the scientific evidence,” Maria Elena Bottazzi, PhD, associate dean of the National School of Tropical Medicine at Baylor College of Medicine in Houston, said in an interview.

After one dose “the immune system is learning, but it’s not ideal. That’s why you need the second dose,” Dr. Bottazzi said. “I appreciate the urgency and the anxiety ... but the data support [that] clinical efficacy requires two doses.”

Another proposed strategy to extend the current supply of COVID-19 vaccines to more Americans involves splitting the current dosage of the Moderna vaccine in half. Officials in the United States and the United Kingdom are reportedly considering this approach. In the United States, the Food and Drug Administration would have to approve any dosing change.
 

Agreeing to disagree

Dr. Wachter shared a link to his opinion piece on Twitter, stating that “We both came to this view because of the slow rollout & the new variant. But it’s a tough call and reasonable people will disagree.”

As predicted, the tweet elicited a number of strong opinions.

“There are no correct answers but there’s data deficiency, plenty of fodder and need for healthy, intellectual debate. That wouldn’t be occurring if there was an ample supply of vaccines,” Eric Topol, MD, director of the Scripps Translational Science Institute and editor-in-chief of Medscape, tweeted on Jan. 3.

“If the problem were with the supply of the vaccine, one might make an argument for focusing on 1st dose. But the problem is in distribution of the vaccine & giving actual doses,” John Grohol, PsyD, tweeted.

“Right now we don’t have a supply issue, we have a distribution issue,” Angela Shen, ScD, MPH, a research scientist in the Vaccine Education Center at Children’s Hospital of Philadelphia, said in an interview. Emergency use authorization for the Johnson & Johnson and other COVID-19 vaccines in development could further boost available supplies, she added.

“The clinical trials studied two doses,” Dr. Shen said. “We don’t have data that one dose is going to have lasting protection.” 
 

Does new variant change equation?

Dr. Wachter and Dr. Jha, in their editorial, cited a quote from former boxing champion Mike Tyson: “Everybody has a plan until they’ve been punched in the mouth.” ‘Punches’ such as the new variant, the high number of cases and deaths in the United States, and other problems prompted them to advocate for the delayed dosing strategy.

“Appreciate the concern for the new variant – I think it’s worth noting that we’re punching ourselves in the mouth with the slow vaccine rollout, which is the first problem to solve,” Jake Quinton, MD, an internist at UCLA Health in Los Angeles, noted on Twitter.

 

Vaccine and public resistance raised

“I agree with the problem but not with the proposed solution, which is guesswork not based on data,” the Jan Grimm Lab at Memorial Sloan Kettering Cancer Center in New York responded to Dr. Wachter and Dr. Jha on Twitter. “There ARE data though that show that 1 shot alone did not elicit sufficient T-cell nor antibody response. This might also lead to mutations resistant to the vaccines. Dangerous!”

Other physicians took to Twitter to point out that changing the recommendations at this point could further erode public confidence in COVID-19 immunization. For example, Deirdre Habermehl, MD, wrote, “We’ve spent months telling the public the best route is to follow the science and now without data think a course correction based on a guesstimate is ok? Public confidence is low enough and the real issue is logistics at this point.”

Dr. Shen and Dr. Bottazzi have disclosed no relevant financial relationships.

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

A proposal to delay administration of the second dose of COVID-19 vaccines – suggested as a strategy to boost the number of people who get some degree of protection from a single immunization with the Pfizer/BioNTech or Moderna vaccines – is inciting a strong debate among clinicians and public health officials.

Proponents argue that getting some degree of protection to a greater number of Americans is worthwhile, particularly as case numbers and hospitalizations continue to rise and with the emergence of a more contagious variant.

Opponents raise concerns about diverting from the two-dose schedule evaluated in clinical trials, including a lack of data on long-term protection from a single dose. They also suggest a longer interval between dosing could increase resistance of SARS-CoV-2 virus.

It is time to consider delaying the second dose, Robert M. Wachter, MD, at the University of California San Francisco, and Ashish Jha, MD, MPH, at Brown University in Providence, R.I., wrote in an opinion piece in The Washington Post Jan. 3. 

The two experts state that supply constraints, distribution bottlenecks, and hundreds of thousands of new infections daily prompted them to change their stance on administering COVID-19 vaccines according to the two-dose clinical trial regimen. Furthermore, they cited a study in the New England Journal of Medicine that suggests 80%-90% efficacy for preventing SARS-CoV-2 infection following one dose of the Moderna vaccine. 

Not everyone agrees one dose is a good idea. “Clinical trials with specific schedules for vaccine dosing – that’s the whole basis of the scientific evidence,” Maria Elena Bottazzi, PhD, associate dean of the National School of Tropical Medicine at Baylor College of Medicine in Houston, said in an interview.

After one dose “the immune system is learning, but it’s not ideal. That’s why you need the second dose,” Dr. Bottazzi said. “I appreciate the urgency and the anxiety ... but the data support [that] clinical efficacy requires two doses.”

Another proposed strategy to extend the current supply of COVID-19 vaccines to more Americans involves splitting the current dosage of the Moderna vaccine in half. Officials in the United States and the United Kingdom are reportedly considering this approach. In the United States, the Food and Drug Administration would have to approve any dosing change.
 

Agreeing to disagree

Dr. Wachter shared a link to his opinion piece on Twitter, stating that “We both came to this view because of the slow rollout & the new variant. But it’s a tough call and reasonable people will disagree.”

As predicted, the tweet elicited a number of strong opinions.

“There are no correct answers but there’s data deficiency, plenty of fodder and need for healthy, intellectual debate. That wouldn’t be occurring if there was an ample supply of vaccines,” Eric Topol, MD, director of the Scripps Translational Science Institute and editor-in-chief of Medscape, tweeted on Jan. 3.

“If the problem were with the supply of the vaccine, one might make an argument for focusing on 1st dose. But the problem is in distribution of the vaccine & giving actual doses,” John Grohol, PsyD, tweeted.

“Right now we don’t have a supply issue, we have a distribution issue,” Angela Shen, ScD, MPH, a research scientist in the Vaccine Education Center at Children’s Hospital of Philadelphia, said in an interview. Emergency use authorization for the Johnson & Johnson and other COVID-19 vaccines in development could further boost available supplies, she added.

“The clinical trials studied two doses,” Dr. Shen said. “We don’t have data that one dose is going to have lasting protection.” 
 

Does new variant change equation?

Dr. Wachter and Dr. Jha, in their editorial, cited a quote from former boxing champion Mike Tyson: “Everybody has a plan until they’ve been punched in the mouth.” ‘Punches’ such as the new variant, the high number of cases and deaths in the United States, and other problems prompted them to advocate for the delayed dosing strategy.

“Appreciate the concern for the new variant – I think it’s worth noting that we’re punching ourselves in the mouth with the slow vaccine rollout, which is the first problem to solve,” Jake Quinton, MD, an internist at UCLA Health in Los Angeles, noted on Twitter.

 

Vaccine and public resistance raised

“I agree with the problem but not with the proposed solution, which is guesswork not based on data,” the Jan Grimm Lab at Memorial Sloan Kettering Cancer Center in New York responded to Dr. Wachter and Dr. Jha on Twitter. “There ARE data though that show that 1 shot alone did not elicit sufficient T-cell nor antibody response. This might also lead to mutations resistant to the vaccines. Dangerous!”

Other physicians took to Twitter to point out that changing the recommendations at this point could further erode public confidence in COVID-19 immunization. For example, Deirdre Habermehl, MD, wrote, “We’ve spent months telling the public the best route is to follow the science and now without data think a course correction based on a guesstimate is ok? Public confidence is low enough and the real issue is logistics at this point.”

Dr. Shen and Dr. Bottazzi have disclosed no relevant financial relationships.

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

An investigational oral selective Janus kinase 1 and JAK2 inhibitor maintained strong efficacy and tolerability for treatment of alopecia areata through 1 year of use in an ongoing open-label extension study of a trio of 24-week, phase 2 randomized trials, James V. Cassella, PhD, reported at the virtual annual congress of the European Academy of Dermatology and Venereology.

“So far, I’d say that the results are very encouraging from this study, as we see good safety and continued stability of the hair regrowth in the open-label extension,” said Dr. Cassella, chief development officer at Concert Pharmaceuticals of Lexington, Mass.

The study drug, known for now as CTP-543, is a deuterium-modified form of the selective JAK1/2 inhibitor ruxolitinib. CTP-543 was expressly designed for treatment of alopecia areata, a chronic autoimmune disease for which no Food and Drug Administration–approved therapy exists. Dr. Cassella characterized alopecia areata as a “devastating and poorly treated” autoimmune disease which affects men, women, and children of all ages and has a lifetime risk of about 2%.

Participants in the open-label extension were typically in their late 30s, with an average disease duration of 3-4 years. Two-thirds were women, and more than three-quarters were White. Their baseline Severity of Alopecia Areata Tool (SALT) score was in the high 80s, indicative of moderate to severe disease.

About 92% of eligible participants from the three phase 2 trials elected to enroll in the long-term extension, a remarkably high participation rate reflective of the major unmet need for effective treatments for this chronic disease.
 

Efficacy

Of the 152 patients who enrolled in an ongoing open-label extension, which had been going for 108 weeks at the time of the presentation, 130 who completed at least 1 year on CTP-543 formed the focus of Dr. Cassella’s presentation. The great majority of participants were on 12 mg twice daily. By week 24 in the original phase 2 trials, SALT scores decreased by more than 50%, compared with baseline, with an average score of about 40. This level of efficacy was maintained through the first 6 months of the extension study – meaning a total of at least 1 year on treatment – in roughly two-thirds of participants, while one-third saw further progressive improvement during the first 6 months of the open-label extension, with SALT scores dropping into the 20-30 range.

“You see remarkable stability of hair regrowth beyond 6 months,” Dr. Cassella commented. Only 2 patients experienced a clear loss of response during the open-label extension.
 

Safety and tolerability

About 15% of patients have dropped out of the long-term study, which in only three cases was because of adverse events. Treatment-emergent adverse events, which occurred in 13% of participants, were rated as mild in 76% and moderate in 21%. The most common were nasopharyngitis, acne, and elevated creatine phosphokinase. Two severe adverse events were deemed “possibly related” to treatment. No new types of side effects have emerged during the long-term extension study. Laboratory monitoring of hemoglobin, neutrophils, and platelets has shown stable levels over time.

An audience member asked how quickly hair loss occurs upon stopping therapy.

“Surprisingly, in the few dose interruptions we’ve had – for changes in hematologic parameters, for example – we have not seen any hair loss in up to a 3-week time period. It’s a very interesting question that we will continue to study,” Dr. Cassella replied. He added: “The general thinking in the community has been, at some point with JAK inhibitors, you will lose your hair if you stop treatment.”

Dr. Cassella is an employee of Concert Pharmaceuticals, and has received company stock.

[email protected]

An investigational oral selective Janus kinase 1 and JAK2 inhibitor maintained strong efficacy and tolerability for treatment of alopecia areata through 1 year of use in an ongoing open-label extension study of a trio of 24-week, phase 2 randomized trials, James V. Cassella, PhD, reported at the virtual annual congress of the European Academy of Dermatology and Venereology.

“So far, I’d say that the results are very encouraging from this study, as we see good safety and continued stability of the hair regrowth in the open-label extension,” said Dr. Cassella, chief development officer at Concert Pharmaceuticals of Lexington, Mass.

The study drug, known for now as CTP-543, is a deuterium-modified form of the selective JAK1/2 inhibitor ruxolitinib. CTP-543 was expressly designed for treatment of alopecia areata, a chronic autoimmune disease for which no Food and Drug Administration–approved therapy exists. Dr. Cassella characterized alopecia areata as a “devastating and poorly treated” autoimmune disease which affects men, women, and children of all ages and has a lifetime risk of about 2%.

Participants in the open-label extension were typically in their late 30s, with an average disease duration of 3-4 years. Two-thirds were women, and more than three-quarters were White. Their baseline Severity of Alopecia Areata Tool (SALT) score was in the high 80s, indicative of moderate to severe disease.

About 92% of eligible participants from the three phase 2 trials elected to enroll in the long-term extension, a remarkably high participation rate reflective of the major unmet need for effective treatments for this chronic disease.
 

Efficacy

Of the 152 patients who enrolled in an ongoing open-label extension, which had been going for 108 weeks at the time of the presentation, 130 who completed at least 1 year on CTP-543 formed the focus of Dr. Cassella’s presentation. The great majority of participants were on 12 mg twice daily. By week 24 in the original phase 2 trials, SALT scores decreased by more than 50%, compared with baseline, with an average score of about 40. This level of efficacy was maintained through the first 6 months of the extension study – meaning a total of at least 1 year on treatment – in roughly two-thirds of participants, while one-third saw further progressive improvement during the first 6 months of the open-label extension, with SALT scores dropping into the 20-30 range.

“You see remarkable stability of hair regrowth beyond 6 months,” Dr. Cassella commented. Only 2 patients experienced a clear loss of response during the open-label extension.
 

Safety and tolerability

About 15% of patients have dropped out of the long-term study, which in only three cases was because of adverse events. Treatment-emergent adverse events, which occurred in 13% of participants, were rated as mild in 76% and moderate in 21%. The most common were nasopharyngitis, acne, and elevated creatine phosphokinase. Two severe adverse events were deemed “possibly related” to treatment. No new types of side effects have emerged during the long-term extension study. Laboratory monitoring of hemoglobin, neutrophils, and platelets has shown stable levels over time.

An audience member asked how quickly hair loss occurs upon stopping therapy.

“Surprisingly, in the few dose interruptions we’ve had – for changes in hematologic parameters, for example – we have not seen any hair loss in up to a 3-week time period. It’s a very interesting question that we will continue to study,” Dr. Cassella replied. He added: “The general thinking in the community has been, at some point with JAK inhibitors, you will lose your hair if you stop treatment.”

Dr. Cassella is an employee of Concert Pharmaceuticals, and has received company stock.

[email protected]

An investigational oral selective Janus kinase 1 and JAK2 inhibitor maintained strong efficacy and tolerability for treatment of alopecia areata through 1 year of use in an ongoing open-label extension study of a trio of 24-week, phase 2 randomized trials, James V. Cassella, PhD, reported at the virtual annual congress of the European Academy of Dermatology and Venereology.

“So far, I’d say that the results are very encouraging from this study, as we see good safety and continued stability of the hair regrowth in the open-label extension,” said Dr. Cassella, chief development officer at Concert Pharmaceuticals of Lexington, Mass.

The study drug, known for now as CTP-543, is a deuterium-modified form of the selective JAK1/2 inhibitor ruxolitinib. CTP-543 was expressly designed for treatment of alopecia areata, a chronic autoimmune disease for which no Food and Drug Administration–approved therapy exists. Dr. Cassella characterized alopecia areata as a “devastating and poorly treated” autoimmune disease which affects men, women, and children of all ages and has a lifetime risk of about 2%.

Participants in the open-label extension were typically in their late 30s, with an average disease duration of 3-4 years. Two-thirds were women, and more than three-quarters were White. Their baseline Severity of Alopecia Areata Tool (SALT) score was in the high 80s, indicative of moderate to severe disease.

About 92% of eligible participants from the three phase 2 trials elected to enroll in the long-term extension, a remarkably high participation rate reflective of the major unmet need for effective treatments for this chronic disease.
 

Efficacy

Of the 152 patients who enrolled in an ongoing open-label extension, which had been going for 108 weeks at the time of the presentation, 130 who completed at least 1 year on CTP-543 formed the focus of Dr. Cassella’s presentation. The great majority of participants were on 12 mg twice daily. By week 24 in the original phase 2 trials, SALT scores decreased by more than 50%, compared with baseline, with an average score of about 40. This level of efficacy was maintained through the first 6 months of the extension study – meaning a total of at least 1 year on treatment – in roughly two-thirds of participants, while one-third saw further progressive improvement during the first 6 months of the open-label extension, with SALT scores dropping into the 20-30 range.

“You see remarkable stability of hair regrowth beyond 6 months,” Dr. Cassella commented. Only 2 patients experienced a clear loss of response during the open-label extension.
 

Safety and tolerability

About 15% of patients have dropped out of the long-term study, which in only three cases was because of adverse events. Treatment-emergent adverse events, which occurred in 13% of participants, were rated as mild in 76% and moderate in 21%. The most common were nasopharyngitis, acne, and elevated creatine phosphokinase. Two severe adverse events were deemed “possibly related” to treatment. No new types of side effects have emerged during the long-term extension study. Laboratory monitoring of hemoglobin, neutrophils, and platelets has shown stable levels over time.

An audience member asked how quickly hair loss occurs upon stopping therapy.

“Surprisingly, in the few dose interruptions we’ve had – for changes in hematologic parameters, for example – we have not seen any hair loss in up to a 3-week time period. It’s a very interesting question that we will continue to study,” Dr. Cassella replied. He added: “The general thinking in the community has been, at some point with JAK inhibitors, you will lose your hair if you stop treatment.”

Dr. Cassella is an employee of Concert Pharmaceuticals, and has received company stock.

[email protected]

This year, Family Practice News is celebrating its 50th anniversary. Look for articles, commentaries, and other special features highlighting the evolution of the specialty in each issue and on MDedge.com/FamilyMedicine throughout 2021.

We plan to address the biggest breakthroughs and most influential people in family medicine over the past 50 years. The publication will also share family physicians’ expectations and hopes for the specialty in the coming years.

Are there any topics you think would be valuable to cover in light of this major milestone? The editorial staff welcomes your suggestions. Please share them by emailing us at [email protected].

Happy New Year, and thank you for supporting us for so many years!

[email protected]

This year, Family Practice News is celebrating its 50th anniversary. Look for articles, commentaries, and other special features highlighting the evolution of the specialty in each issue and on MDedge.com/FamilyMedicine throughout 2021.

We plan to address the biggest breakthroughs and most influential people in family medicine over the past 50 years. The publication will also share family physicians’ expectations and hopes for the specialty in the coming years.

Are there any topics you think would be valuable to cover in light of this major milestone? The editorial staff welcomes your suggestions. Please share them by emailing us at [email protected].

Happy New Year, and thank you for supporting us for so many years!

[email protected]

This year, Family Practice News is celebrating its 50th anniversary. Look for articles, commentaries, and other special features highlighting the evolution of the specialty in each issue and on MDedge.com/FamilyMedicine throughout 2021.

We plan to address the biggest breakthroughs and most influential people in family medicine over the past 50 years. The publication will also share family physicians’ expectations and hopes for the specialty in the coming years.

Are there any topics you think would be valuable to cover in light of this major milestone? The editorial staff welcomes your suggestions. Please share them by emailing us at [email protected].

Happy New Year, and thank you for supporting us for so many years!

[email protected]

Dr. Sara Hurvitz, Director of the Breast Cancer Clinical Trials Program at UCLA, reviews key updates in HER2-positive metastatic breast cancer studies presented during the 2020 San Antonio Breast Cancer Symposium (SABCS), which was held virtually in December.

A sub-analysis of patients who had central nervous system disease at baseline demonstrated improved outcomes with neratinib plus capecitabine compared with those receiving lapatinib plus capecitabine in the NALA trial.

Updated results from the DESTINY-breast01 study of trastuzumab deruxtecan show encouraging results in progression-free survival and early overall survival and high rates of durable responses in a heavily pretreated group of patients with metastatic breast cancer, consistent with early results.

In the HER2CLIMB study, patients treated with tucatinib in combination with trastuzumab and capecitabine had clinically meaningful improvement in progression-free survival, overall survival, and objective response rate independent of HR status compared with placebo, and patients with HR+ and HR- breast cancer with brain metastases experienced similar benefits.

--

Sara A. Hurvitz, MD, FACP, Professor of Medicine. Director, Breast Cancer Clinical Trials Program, Division of Hematology-Oncology David Geffen School of Medicine at UCLA
Medical Director, Clinical Research Unit, UCLA Jonsson Comprehensive Cancer Center.

Dr. Hurvitz has received research grants from: Ambrx; Amgen Inc.; Bayer HealthCare Pharmaceuticals; Daiichi Sankyo, Inc.; Dignitana AB; Eli Lilly and Company; Genentech, Inc.; GlaxoSmithKline; Immunomedics; MacroGenics, Inc.; Novartis Pharmaceuticals Corporation; OBI Pharma, Inc.; Pfizer Inc; Pieris Pharmaceuticals Inc; Puma Biotechnology; Radius Health; Roche Pharma; sanofi-aventis; Seattle Genetics, Inc.

Dr. Sara Hurvitz, Director of the Breast Cancer Clinical Trials Program at UCLA, reviews key updates in HER2-positive metastatic breast cancer studies presented during the 2020 San Antonio Breast Cancer Symposium (SABCS), which was held virtually in December.

A sub-analysis of patients who had central nervous system disease at baseline demonstrated improved outcomes with neratinib plus capecitabine compared with those receiving lapatinib plus capecitabine in the NALA trial.

Updated results from the DESTINY-breast01 study of trastuzumab deruxtecan show encouraging results in progression-free survival and early overall survival and high rates of durable responses in a heavily pretreated group of patients with metastatic breast cancer, consistent with early results.

In the HER2CLIMB study, patients treated with tucatinib in combination with trastuzumab and capecitabine had clinically meaningful improvement in progression-free survival, overall survival, and objective response rate independent of HR status compared with placebo, and patients with HR+ and HR- breast cancer with brain metastases experienced similar benefits.

--

Sara A. Hurvitz, MD, FACP, Professor of Medicine. Director, Breast Cancer Clinical Trials Program, Division of Hematology-Oncology David Geffen School of Medicine at UCLA
Medical Director, Clinical Research Unit, UCLA Jonsson Comprehensive Cancer Center.

Dr. Hurvitz has received research grants from: Ambrx; Amgen Inc.; Bayer HealthCare Pharmaceuticals; Daiichi Sankyo, Inc.; Dignitana AB; Eli Lilly and Company; Genentech, Inc.; GlaxoSmithKline; Immunomedics; MacroGenics, Inc.; Novartis Pharmaceuticals Corporation; OBI Pharma, Inc.; Pfizer Inc; Pieris Pharmaceuticals Inc; Puma Biotechnology; Radius Health; Roche Pharma; sanofi-aventis; Seattle Genetics, Inc.

Dr. Sara Hurvitz, Director of the Breast Cancer Clinical Trials Program at UCLA, reviews key updates in HER2-positive metastatic breast cancer studies presented during the 2020 San Antonio Breast Cancer Symposium (SABCS), which was held virtually in December.

A sub-analysis of patients who had central nervous system disease at baseline demonstrated improved outcomes with neratinib plus capecitabine compared with those receiving lapatinib plus capecitabine in the NALA trial.

Updated results from the DESTINY-breast01 study of trastuzumab deruxtecan show encouraging results in progression-free survival and early overall survival and high rates of durable responses in a heavily pretreated group of patients with metastatic breast cancer, consistent with early results.

In the HER2CLIMB study, patients treated with tucatinib in combination with trastuzumab and capecitabine had clinically meaningful improvement in progression-free survival, overall survival, and objective response rate independent of HR status compared with placebo, and patients with HR+ and HR- breast cancer with brain metastases experienced similar benefits.

--

Sara A. Hurvitz, MD, FACP, Professor of Medicine. Director, Breast Cancer Clinical Trials Program, Division of Hematology-Oncology David Geffen School of Medicine at UCLA
Medical Director, Clinical Research Unit, UCLA Jonsson Comprehensive Cancer Center.

Dr. Hurvitz has received research grants from: Ambrx; Amgen Inc.; Bayer HealthCare Pharmaceuticals; Daiichi Sankyo, Inc.; Dignitana AB; Eli Lilly and Company; Genentech, Inc.; GlaxoSmithKline; Immunomedics; MacroGenics, Inc.; Novartis Pharmaceuticals Corporation; OBI Pharma, Inc.; Pfizer Inc; Pieris Pharmaceuticals Inc; Puma Biotechnology; Radius Health; Roche Pharma; sanofi-aventis; Seattle Genetics, Inc.

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SARS-CoV-2 can invade the brain and directly act on brain cells, causing neuroinflammation, new animal research suggests. Investigators injected spike 1 (S1), which is found on the tufts of the “red spikes” of the virus, into mice and found that it crossed the blood-brain barrier (BBB) and was taken up not only by brain regions and the brain space but also by other organs – specifically, the lungs, spleen, liver, and kidneys.

“We found that the S1 protein, which is the protein COVID-19 uses to ‘grab onto’ cells, crosses the BBB and is a good model of what the virus does when it enters the brain,” lead author William A. Banks, MD, professor of medicine, University of Washington, Seattle, said in an interview.

“When proteins such as the S1 protein become detached from the virus, they can enter the brain and cause mayhem, causing the brain to release cytokines, which, in turn, cause inflammation and subsequent neurotoxicity,” said Dr. Banks, associate chief of staff and a researcher at the Puget Sound Veterans Affairs Healthcare System.

The study was published online in Nature Neuroscience.
 

Neurologic symptoms

COVID-19 is associated with a variety of central nervous system symptoms, including the loss of taste and smell, headaches, confusion, stroke, and cerebral hemorrhage, the investigators noted.

Dr. Banks explained that SARS-CoV-2 may enter the brain by crossing the BBB, acting directly on the brain centers responsible for other body functions. The respiratory symptoms of COVID-19 may therefore result partly from the invasion of the areas of the brain responsible for respiratory functions, not only from the virus’ action at the site of the lungs.

The researchers set out to assess whether a particular viral protein – S1, which is a subunit of the viral spike protein – could cross the BBB or enter other organs when injected into mice. They found that, when intravenously injected S1 (I-S1) was cleared from the blood, tissues in multiple organs, including the lung, spleen, kidney, and liver, took it up.

Notably, uptake of I-S1 was higher in the liver, “suggesting that this protein is cleared from the blood predominantly by the liver,” Dr. Banks said. In addition, uptake by the lungs is “important, because that’s where many of the effects of the virus are,” he added.

The researchers found that I-S1 in the brains of the mice was “mostly degraded” 30 minutes following injection. “This indicates that I-S1 enters the BBB intact but is eventually degraded in the brain,” they wrote.

Moreover, by 30 minutes, more than half of the I-S1 proteins had crossed the capillary wall and had fully entered into the brain parenchymal and interstitial fluid spaces, as well as other regions.
 

More severe outcomes in men

The researchers then induced an inflammatory state in the mice through injection of lipopolysaccharide (LPS) and found that inflammation increased I-S1 uptake in both the brain and the lung (where uptake was increased by 101%). “These results show that inflammation could increase S1 toxicity for lung tissue by increasing its uptake,” the authors suggested. Moreover, inflammation also increased the entry of I-S1 into the brain, “likely due to BBB disruption.”

In human beings, male sex and APOE4 genotype are risk factors for both contracting COVID-19 and having a poor outcome, the authors noted. As a result, they examined I-S1 uptake in male and female mice that expressed human APOE3 or APOE4 (induced by a mouse ApoE promoter).

Multiple-comparison tests showed that among male mice that expressed human APOE3, the “fastest I-S1 uptake” was in the olfactory bulb, liver, and kidney. Female mice displayed increased APOE3 uptake in the spleen.

“This observation might relate to the increased susceptibility of men to more severe COVID-19 outcomes,” coauthor Jacob Raber, PhD, professor, departments of behavioral neuroscience, neurology, and radiation medicine, Oregon Health & Science University, Portland, said in a press release.

In addition to intravenous I-S1 injection, the researchers also investigated the effects of intranasal administration. They found that, although it also entered the brain, it did so at levels roughly 10 times lower than those induced by intravenous administration.
 

“Frightening tricks”

Dr. Banks said his laboratory has studied the BBB in conditions such as Alzheimer’s disease, obesity, diabetes, and HIV. “Our experience with viruses is that they do an incredible number of things and have a frightening number of tricks,” he said. In this case, “the virus is probably causing inflammation by releasing cytokines elsewhere in the body that get into the brain through the BBB.” Conversely, “the virus itself may enter the brain by crossing the BBB and directly cause brain cells to release their own cytokines,” he added.

An additional finding of the study is that, whatever the S1 protein does in the brain is a model for what the entire virus itself does, because these proteins often bring the viruses along with them, he added.

Dr. Banks said the clinical implications of the findings are that antibodies from those who have already had COVID-19 could potentially be directed against S1. Similarly, he added, so can COVID-19 vaccines, which induce production of S1.

“When an antibody locks onto something, it prevents it from crossing the BBB,” Dr. Banks noted.
 

Confirmatory findings

Commenting on the study, Howard E. Gendelman, MD, Margaret R. Larson Professor of Internal Medicine and Infectious Diseases and professor and chair of the department of pharmacology and experimental neuroscience, University of Nebraska, Omaha, said the study is confirmatory.

“What this paper highlights, and we have known for a long time, is that COVID-19 is a systemic, not only a respiratory, disease involving many organs and tissues and can yield not only pulmonary problems but also a whole host of cardiac, brain, and kidney problems,” he said.

“So the fact that these proteins are getting in [the brain] and are able to induce a reaction in the brain itself, and this is part of the complex progressive nature of COVID-19, is an important finding,” added Dr. Gendelman, director of the center for neurodegenerative disorders at the university. He was not involved with the study.

The study was supported by the Veterans Affairs Puget Sound Healthcare System and by grants from the National Institutes of Health. The authors and Dr. Gendelman have disclosed no relevant financial relationships.

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

SARS-CoV-2 can invade the brain and directly act on brain cells, causing neuroinflammation, new animal research suggests. Investigators injected spike 1 (S1), which is found on the tufts of the “red spikes” of the virus, into mice and found that it crossed the blood-brain barrier (BBB) and was taken up not only by brain regions and the brain space but also by other organs – specifically, the lungs, spleen, liver, and kidneys.

“We found that the S1 protein, which is the protein COVID-19 uses to ‘grab onto’ cells, crosses the BBB and is a good model of what the virus does when it enters the brain,” lead author William A. Banks, MD, professor of medicine, University of Washington, Seattle, said in an interview.

“When proteins such as the S1 protein become detached from the virus, they can enter the brain and cause mayhem, causing the brain to release cytokines, which, in turn, cause inflammation and subsequent neurotoxicity,” said Dr. Banks, associate chief of staff and a researcher at the Puget Sound Veterans Affairs Healthcare System.

The study was published online in Nature Neuroscience.
 

Neurologic symptoms

COVID-19 is associated with a variety of central nervous system symptoms, including the loss of taste and smell, headaches, confusion, stroke, and cerebral hemorrhage, the investigators noted.

Dr. Banks explained that SARS-CoV-2 may enter the brain by crossing the BBB, acting directly on the brain centers responsible for other body functions. The respiratory symptoms of COVID-19 may therefore result partly from the invasion of the areas of the brain responsible for respiratory functions, not only from the virus’ action at the site of the lungs.

The researchers set out to assess whether a particular viral protein – S1, which is a subunit of the viral spike protein – could cross the BBB or enter other organs when injected into mice. They found that, when intravenously injected S1 (I-S1) was cleared from the blood, tissues in multiple organs, including the lung, spleen, kidney, and liver, took it up.

Notably, uptake of I-S1 was higher in the liver, “suggesting that this protein is cleared from the blood predominantly by the liver,” Dr. Banks said. In addition, uptake by the lungs is “important, because that’s where many of the effects of the virus are,” he added.

The researchers found that I-S1 in the brains of the mice was “mostly degraded” 30 minutes following injection. “This indicates that I-S1 enters the BBB intact but is eventually degraded in the brain,” they wrote.

Moreover, by 30 minutes, more than half of the I-S1 proteins had crossed the capillary wall and had fully entered into the brain parenchymal and interstitial fluid spaces, as well as other regions.
 

More severe outcomes in men

The researchers then induced an inflammatory state in the mice through injection of lipopolysaccharide (LPS) and found that inflammation increased I-S1 uptake in both the brain and the lung (where uptake was increased by 101%). “These results show that inflammation could increase S1 toxicity for lung tissue by increasing its uptake,” the authors suggested. Moreover, inflammation also increased the entry of I-S1 into the brain, “likely due to BBB disruption.”

In human beings, male sex and APOE4 genotype are risk factors for both contracting COVID-19 and having a poor outcome, the authors noted. As a result, they examined I-S1 uptake in male and female mice that expressed human APOE3 or APOE4 (induced by a mouse ApoE promoter).

Multiple-comparison tests showed that among male mice that expressed human APOE3, the “fastest I-S1 uptake” was in the olfactory bulb, liver, and kidney. Female mice displayed increased APOE3 uptake in the spleen.

“This observation might relate to the increased susceptibility of men to more severe COVID-19 outcomes,” coauthor Jacob Raber, PhD, professor, departments of behavioral neuroscience, neurology, and radiation medicine, Oregon Health & Science University, Portland, said in a press release.

In addition to intravenous I-S1 injection, the researchers also investigated the effects of intranasal administration. They found that, although it also entered the brain, it did so at levels roughly 10 times lower than those induced by intravenous administration.
 

“Frightening tricks”

Dr. Banks said his laboratory has studied the BBB in conditions such as Alzheimer’s disease, obesity, diabetes, and HIV. “Our experience with viruses is that they do an incredible number of things and have a frightening number of tricks,” he said. In this case, “the virus is probably causing inflammation by releasing cytokines elsewhere in the body that get into the brain through the BBB.” Conversely, “the virus itself may enter the brain by crossing the BBB and directly cause brain cells to release their own cytokines,” he added.

An additional finding of the study is that, whatever the S1 protein does in the brain is a model for what the entire virus itself does, because these proteins often bring the viruses along with them, he added.

Dr. Banks said the clinical implications of the findings are that antibodies from those who have already had COVID-19 could potentially be directed against S1. Similarly, he added, so can COVID-19 vaccines, which induce production of S1.

“When an antibody locks onto something, it prevents it from crossing the BBB,” Dr. Banks noted.
 

Confirmatory findings

Commenting on the study, Howard E. Gendelman, MD, Margaret R. Larson Professor of Internal Medicine and Infectious Diseases and professor and chair of the department of pharmacology and experimental neuroscience, University of Nebraska, Omaha, said the study is confirmatory.

“What this paper highlights, and we have known for a long time, is that COVID-19 is a systemic, not only a respiratory, disease involving many organs and tissues and can yield not only pulmonary problems but also a whole host of cardiac, brain, and kidney problems,” he said.

“So the fact that these proteins are getting in [the brain] and are able to induce a reaction in the brain itself, and this is part of the complex progressive nature of COVID-19, is an important finding,” added Dr. Gendelman, director of the center for neurodegenerative disorders at the university. He was not involved with the study.

The study was supported by the Veterans Affairs Puget Sound Healthcare System and by grants from the National Institutes of Health. The authors and Dr. Gendelman have disclosed no relevant financial relationships.

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

SARS-CoV-2 can invade the brain and directly act on brain cells, causing neuroinflammation, new animal research suggests. Investigators injected spike 1 (S1), which is found on the tufts of the “red spikes” of the virus, into mice and found that it crossed the blood-brain barrier (BBB) and was taken up not only by brain regions and the brain space but also by other organs – specifically, the lungs, spleen, liver, and kidneys.

“We found that the S1 protein, which is the protein COVID-19 uses to ‘grab onto’ cells, crosses the BBB and is a good model of what the virus does when it enters the brain,” lead author William A. Banks, MD, professor of medicine, University of Washington, Seattle, said in an interview.

“When proteins such as the S1 protein become detached from the virus, they can enter the brain and cause mayhem, causing the brain to release cytokines, which, in turn, cause inflammation and subsequent neurotoxicity,” said Dr. Banks, associate chief of staff and a researcher at the Puget Sound Veterans Affairs Healthcare System.

The study was published online in Nature Neuroscience.
 

Neurologic symptoms

COVID-19 is associated with a variety of central nervous system symptoms, including the loss of taste and smell, headaches, confusion, stroke, and cerebral hemorrhage, the investigators noted.

Dr. Banks explained that SARS-CoV-2 may enter the brain by crossing the BBB, acting directly on the brain centers responsible for other body functions. The respiratory symptoms of COVID-19 may therefore result partly from the invasion of the areas of the brain responsible for respiratory functions, not only from the virus’ action at the site of the lungs.

The researchers set out to assess whether a particular viral protein – S1, which is a subunit of the viral spike protein – could cross the BBB or enter other organs when injected into mice. They found that, when intravenously injected S1 (I-S1) was cleared from the blood, tissues in multiple organs, including the lung, spleen, kidney, and liver, took it up.

Notably, uptake of I-S1 was higher in the liver, “suggesting that this protein is cleared from the blood predominantly by the liver,” Dr. Banks said. In addition, uptake by the lungs is “important, because that’s where many of the effects of the virus are,” he added.

The researchers found that I-S1 in the brains of the mice was “mostly degraded” 30 minutes following injection. “This indicates that I-S1 enters the BBB intact but is eventually degraded in the brain,” they wrote.

Moreover, by 30 minutes, more than half of the I-S1 proteins had crossed the capillary wall and had fully entered into the brain parenchymal and interstitial fluid spaces, as well as other regions.
 

More severe outcomes in men

The researchers then induced an inflammatory state in the mice through injection of lipopolysaccharide (LPS) and found that inflammation increased I-S1 uptake in both the brain and the lung (where uptake was increased by 101%). “These results show that inflammation could increase S1 toxicity for lung tissue by increasing its uptake,” the authors suggested. Moreover, inflammation also increased the entry of I-S1 into the brain, “likely due to BBB disruption.”

In human beings, male sex and APOE4 genotype are risk factors for both contracting COVID-19 and having a poor outcome, the authors noted. As a result, they examined I-S1 uptake in male and female mice that expressed human APOE3 or APOE4 (induced by a mouse ApoE promoter).

Multiple-comparison tests showed that among male mice that expressed human APOE3, the “fastest I-S1 uptake” was in the olfactory bulb, liver, and kidney. Female mice displayed increased APOE3 uptake in the spleen.

“This observation might relate to the increased susceptibility of men to more severe COVID-19 outcomes,” coauthor Jacob Raber, PhD, professor, departments of behavioral neuroscience, neurology, and radiation medicine, Oregon Health & Science University, Portland, said in a press release.

In addition to intravenous I-S1 injection, the researchers also investigated the effects of intranasal administration. They found that, although it also entered the brain, it did so at levels roughly 10 times lower than those induced by intravenous administration.
 

“Frightening tricks”

Dr. Banks said his laboratory has studied the BBB in conditions such as Alzheimer’s disease, obesity, diabetes, and HIV. “Our experience with viruses is that they do an incredible number of things and have a frightening number of tricks,” he said. In this case, “the virus is probably causing inflammation by releasing cytokines elsewhere in the body that get into the brain through the BBB.” Conversely, “the virus itself may enter the brain by crossing the BBB and directly cause brain cells to release their own cytokines,” he added.

An additional finding of the study is that, whatever the S1 protein does in the brain is a model for what the entire virus itself does, because these proteins often bring the viruses along with them, he added.

Dr. Banks said the clinical implications of the findings are that antibodies from those who have already had COVID-19 could potentially be directed against S1. Similarly, he added, so can COVID-19 vaccines, which induce production of S1.

“When an antibody locks onto something, it prevents it from crossing the BBB,” Dr. Banks noted.
 

Confirmatory findings

Commenting on the study, Howard E. Gendelman, MD, Margaret R. Larson Professor of Internal Medicine and Infectious Diseases and professor and chair of the department of pharmacology and experimental neuroscience, University of Nebraska, Omaha, said the study is confirmatory.

“What this paper highlights, and we have known for a long time, is that COVID-19 is a systemic, not only a respiratory, disease involving many organs and tissues and can yield not only pulmonary problems but also a whole host of cardiac, brain, and kidney problems,” he said.

“So the fact that these proteins are getting in [the brain] and are able to induce a reaction in the brain itself, and this is part of the complex progressive nature of COVID-19, is an important finding,” added Dr. Gendelman, director of the center for neurodegenerative disorders at the university. He was not involved with the study.

The study was supported by the Veterans Affairs Puget Sound Healthcare System and by grants from the National Institutes of Health. The authors and Dr. Gendelman have disclosed no relevant financial relationships.

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

Clinicians who care for patients with rheumatic and musculoskeletal diseases (RMDs) can now refer to a new set of strategies and points to consider from a European League Against Rheumatism (EULAR) task force in building a patient-centered approach to improve adherence to treatments.

Nonadherence to treatments is concerning given that 30%-80% of patients who have RMDs are thought to not follow a recommended treatment plan according to their physicians’ instructions, according to first author Valentin Ritschl of the Medical University of Vienna and colleagues.

“The problem of poor adherence is addressed in some EULAR recommendations/points to consider on the management of specific health conditions or on the role of professionals,” Mr. Ritschl said in an interview. “However, all these recommendations focus on limited aspects of nonadherence and do not cover the multifaceted nature of this phenomenon.”

Mr. Ritschl and colleagues conducted an extensive systematic literature review, the results of which they presented to a task force consisting of a panel of international experts hailing from 12 different countries. The task force included rheumatologists and other health professionals in rheumatology, as well as patient representatives.

The collaboration resulted in investigators crafting a definition of adherence in addition to drafting four overarching principles and nine points to consider, which were published Dec. 18 in Annals of the Rheumatic Diseases.

They defined adherence as “the extent to which a person’s behavior corresponds with the agreed prescription, of pharmacological or nonpharmacological treatments, by a health care provider.”

The four overarching principles emphasize the following concepts: that adherence affects outcomes in people who have RMDs; the importance of shared decision-making, with the understanding that the adherence describes the patient’s behavior “following an agreed prescription”; that numerous factors can affect adherence; and the notion of adherence being a dynamic process that, consequently, requires continuous evaluation.

Among the nine points to consider, Mr. Ritschl and coauthors encouraged all health care providers involved in caring for RMD patients to assume responsibility for promoting adherence. Practitioners should also strive to create an ongoing, open dialogue to discuss adherence, especially in cases in which the patient’s RMD is not well controlled. The patient-centered recommendations include taking into account the patient’s goals and preferences because these greatly contribute to the patient’s ability to adhere to any medication regimen. Another arm of that exploration also requires the medical professional to evaluate any circumstances that could bear a negative effect on the patient’s adherence – whether it be medication access issues related to cost or availability, or functional challenges such as memory, motivation, or complexity of the medication regimen.

SDI Productions/E+

Mr. Ritschl believed the task force’s recommendations will add value and help improve overall outcomes in RMD population management.

“Until today, there are no recommendations or points to consider developed in order to support our patients to be adherent to the agreed treatment plan,” he said. “In our project/initiative, we therefore developed for the first time points to consider to detect, assess, and manage nonadherence in people with RMDs.”

Additionally, the recommendations offer some strategic insights to help improve clinical trials because the deleterious effects of nonadherence also affect study results.

Looking ahead, Mr. Ritschl said randomized, controlled trials are necessary to test strategies that might improve adherence. He strongly emphasized the importance of designing future research studies that are heavily patient centered and effective for shared decision-making.

The project was funded by EULAR. Mr. Ritschl reported having no disclosures, but many of his coauthors reported financial relationships with pharmaceutical companies.

SOURCE: Ritschl V et al. Ann Rheum Dis. 2020 Dec 18. doi: 10.1136/annrheumdis-2020-218986.

Clinicians who care for patients with rheumatic and musculoskeletal diseases (RMDs) can now refer to a new set of strategies and points to consider from a European League Against Rheumatism (EULAR) task force in building a patient-centered approach to improve adherence to treatments.

Nonadherence to treatments is concerning given that 30%-80% of patients who have RMDs are thought to not follow a recommended treatment plan according to their physicians’ instructions, according to first author Valentin Ritschl of the Medical University of Vienna and colleagues.

“The problem of poor adherence is addressed in some EULAR recommendations/points to consider on the management of specific health conditions or on the role of professionals,” Mr. Ritschl said in an interview. “However, all these recommendations focus on limited aspects of nonadherence and do not cover the multifaceted nature of this phenomenon.”

Mr. Ritschl and colleagues conducted an extensive systematic literature review, the results of which they presented to a task force consisting of a panel of international experts hailing from 12 different countries. The task force included rheumatologists and other health professionals in rheumatology, as well as patient representatives.

The collaboration resulted in investigators crafting a definition of adherence in addition to drafting four overarching principles and nine points to consider, which were published Dec. 18 in Annals of the Rheumatic Diseases.

They defined adherence as “the extent to which a person’s behavior corresponds with the agreed prescription, of pharmacological or nonpharmacological treatments, by a health care provider.”

The four overarching principles emphasize the following concepts: that adherence affects outcomes in people who have RMDs; the importance of shared decision-making, with the understanding that the adherence describes the patient’s behavior “following an agreed prescription”; that numerous factors can affect adherence; and the notion of adherence being a dynamic process that, consequently, requires continuous evaluation.

Among the nine points to consider, Mr. Ritschl and coauthors encouraged all health care providers involved in caring for RMD patients to assume responsibility for promoting adherence. Practitioners should also strive to create an ongoing, open dialogue to discuss adherence, especially in cases in which the patient’s RMD is not well controlled. The patient-centered recommendations include taking into account the patient’s goals and preferences because these greatly contribute to the patient’s ability to adhere to any medication regimen. Another arm of that exploration also requires the medical professional to evaluate any circumstances that could bear a negative effect on the patient’s adherence – whether it be medication access issues related to cost or availability, or functional challenges such as memory, motivation, or complexity of the medication regimen.

SDI Productions/E+

Mr. Ritschl believed the task force’s recommendations will add value and help improve overall outcomes in RMD population management.

“Until today, there are no recommendations or points to consider developed in order to support our patients to be adherent to the agreed treatment plan,” he said. “In our project/initiative, we therefore developed for the first time points to consider to detect, assess, and manage nonadherence in people with RMDs.”

Additionally, the recommendations offer some strategic insights to help improve clinical trials because the deleterious effects of nonadherence also affect study results.

Looking ahead, Mr. Ritschl said randomized, controlled trials are necessary to test strategies that might improve adherence. He strongly emphasized the importance of designing future research studies that are heavily patient centered and effective for shared decision-making.

The project was funded by EULAR. Mr. Ritschl reported having no disclosures, but many of his coauthors reported financial relationships with pharmaceutical companies.

SOURCE: Ritschl V et al. Ann Rheum Dis. 2020 Dec 18. doi: 10.1136/annrheumdis-2020-218986.

Clinicians who care for patients with rheumatic and musculoskeletal diseases (RMDs) can now refer to a new set of strategies and points to consider from a European League Against Rheumatism (EULAR) task force in building a patient-centered approach to improve adherence to treatments.

Nonadherence to treatments is concerning given that 30%-80% of patients who have RMDs are thought to not follow a recommended treatment plan according to their physicians’ instructions, according to first author Valentin Ritschl of the Medical University of Vienna and colleagues.

“The problem of poor adherence is addressed in some EULAR recommendations/points to consider on the management of specific health conditions or on the role of professionals,” Mr. Ritschl said in an interview. “However, all these recommendations focus on limited aspects of nonadherence and do not cover the multifaceted nature of this phenomenon.”

Mr. Ritschl and colleagues conducted an extensive systematic literature review, the results of which they presented to a task force consisting of a panel of international experts hailing from 12 different countries. The task force included rheumatologists and other health professionals in rheumatology, as well as patient representatives.

The collaboration resulted in investigators crafting a definition of adherence in addition to drafting four overarching principles and nine points to consider, which were published Dec. 18 in Annals of the Rheumatic Diseases.

They defined adherence as “the extent to which a person’s behavior corresponds with the agreed prescription, of pharmacological or nonpharmacological treatments, by a health care provider.”

The four overarching principles emphasize the following concepts: that adherence affects outcomes in people who have RMDs; the importance of shared decision-making, with the understanding that the adherence describes the patient’s behavior “following an agreed prescription”; that numerous factors can affect adherence; and the notion of adherence being a dynamic process that, consequently, requires continuous evaluation.

Among the nine points to consider, Mr. Ritschl and coauthors encouraged all health care providers involved in caring for RMD patients to assume responsibility for promoting adherence. Practitioners should also strive to create an ongoing, open dialogue to discuss adherence, especially in cases in which the patient’s RMD is not well controlled. The patient-centered recommendations include taking into account the patient’s goals and preferences because these greatly contribute to the patient’s ability to adhere to any medication regimen. Another arm of that exploration also requires the medical professional to evaluate any circumstances that could bear a negative effect on the patient’s adherence – whether it be medication access issues related to cost or availability, or functional challenges such as memory, motivation, or complexity of the medication regimen.

SDI Productions/E+

Mr. Ritschl believed the task force’s recommendations will add value and help improve overall outcomes in RMD population management.

“Until today, there are no recommendations or points to consider developed in order to support our patients to be adherent to the agreed treatment plan,” he said. “In our project/initiative, we therefore developed for the first time points to consider to detect, assess, and manage nonadherence in people with RMDs.”

Additionally, the recommendations offer some strategic insights to help improve clinical trials because the deleterious effects of nonadherence also affect study results.

Looking ahead, Mr. Ritschl said randomized, controlled trials are necessary to test strategies that might improve adherence. He strongly emphasized the importance of designing future research studies that are heavily patient centered and effective for shared decision-making.

The project was funded by EULAR. Mr. Ritschl reported having no disclosures, but many of his coauthors reported financial relationships with pharmaceutical companies.

SOURCE: Ritschl V et al. Ann Rheum Dis. 2020 Dec 18. doi: 10.1136/annrheumdis-2020-218986.

The United States started 2021 they way it ended 2020: Setting new records amidst the coronavirus pandemic.

Courtesy NIAID-RML

The country passed the 20 million mark for coronavirus cases on Friday, setting the mark sometime around noon, according to Johns Hopkins University’s COVID-19 tracker. The total is nearly twice as many as the next worst country – India, which has 10.28 million cases.

Along with the case count, more than 346,000 Americans have now died of COVID-19, the disease caused by the coronavirus. That is 77% more fatalities than Brazil, which ranks second globally with 194,949 deaths.

More than 125,370 coronavirus patients were hospitalized on Thursday, the fourth record-setting day in a row, according to the COVID Tracking Project.

Going by official tallies, it took 292 days for the United States to reach its first 10 million cases, and just 54 more days to double it, CNN reported.

Meanwhile, 12.41 million doses of COVID-19 vaccines have been distributed in the United States as of Wednesday, according to the Centers for Disease Control and Prevention. Yet only 2.8 million people have received the first of a two-shot regimen.

The slower-than-hoped-for rollout of the Pfizer and Moderna vaccines comes as a new variant of the coronavirus has emerged in a third state. Florida officials announced a confirmed case of the new variant – believed to have originated in the United Kingdom – in Martin County in southeast Florida.

The state health department said on Twitter that the patient is a man in his 20s with no history of travel. The department said it is working with the CDC to investigate.

The variant has also been confirmed in cases in Colorado and California. It is believed to be more contagious. The BBC reported that the new variant increases the reproduction, or “R number,” by 0.4 and 0.7. The UK’s most recent R number has been estimated at 1.1-1.3, meaning anyone who has the coronavirus could be assumed to spread it to up to 1.3 people.

The R number needs to be below 1.0 for the spread of the virus to fall.

“There is a huge difference in how easily the variant virus spreads,” Professor Axel Gandy of London’s Imperial College told BBC News. “This is the most serious change in the virus since the epidemic began.”

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

The United States started 2021 they way it ended 2020: Setting new records amidst the coronavirus pandemic.

Courtesy NIAID-RML

The country passed the 20 million mark for coronavirus cases on Friday, setting the mark sometime around noon, according to Johns Hopkins University’s COVID-19 tracker. The total is nearly twice as many as the next worst country – India, which has 10.28 million cases.

Along with the case count, more than 346,000 Americans have now died of COVID-19, the disease caused by the coronavirus. That is 77% more fatalities than Brazil, which ranks second globally with 194,949 deaths.

More than 125,370 coronavirus patients were hospitalized on Thursday, the fourth record-setting day in a row, according to the COVID Tracking Project.

Going by official tallies, it took 292 days for the United States to reach its first 10 million cases, and just 54 more days to double it, CNN reported.

Meanwhile, 12.41 million doses of COVID-19 vaccines have been distributed in the United States as of Wednesday, according to the Centers for Disease Control and Prevention. Yet only 2.8 million people have received the first of a two-shot regimen.

The slower-than-hoped-for rollout of the Pfizer and Moderna vaccines comes as a new variant of the coronavirus has emerged in a third state. Florida officials announced a confirmed case of the new variant – believed to have originated in the United Kingdom – in Martin County in southeast Florida.

The state health department said on Twitter that the patient is a man in his 20s with no history of travel. The department said it is working with the CDC to investigate.

The variant has also been confirmed in cases in Colorado and California. It is believed to be more contagious. The BBC reported that the new variant increases the reproduction, or “R number,” by 0.4 and 0.7. The UK’s most recent R number has been estimated at 1.1-1.3, meaning anyone who has the coronavirus could be assumed to spread it to up to 1.3 people.

The R number needs to be below 1.0 for the spread of the virus to fall.

“There is a huge difference in how easily the variant virus spreads,” Professor Axel Gandy of London’s Imperial College told BBC News. “This is the most serious change in the virus since the epidemic began.”

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

The United States started 2021 they way it ended 2020: Setting new records amidst the coronavirus pandemic.

Courtesy NIAID-RML

The country passed the 20 million mark for coronavirus cases on Friday, setting the mark sometime around noon, according to Johns Hopkins University’s COVID-19 tracker. The total is nearly twice as many as the next worst country – India, which has 10.28 million cases.

Along with the case count, more than 346,000 Americans have now died of COVID-19, the disease caused by the coronavirus. That is 77% more fatalities than Brazil, which ranks second globally with 194,949 deaths.

More than 125,370 coronavirus patients were hospitalized on Thursday, the fourth record-setting day in a row, according to the COVID Tracking Project.

Going by official tallies, it took 292 days for the United States to reach its first 10 million cases, and just 54 more days to double it, CNN reported.

Meanwhile, 12.41 million doses of COVID-19 vaccines have been distributed in the United States as of Wednesday, according to the Centers for Disease Control and Prevention. Yet only 2.8 million people have received the first of a two-shot regimen.

The slower-than-hoped-for rollout of the Pfizer and Moderna vaccines comes as a new variant of the coronavirus has emerged in a third state. Florida officials announced a confirmed case of the new variant – believed to have originated in the United Kingdom – in Martin County in southeast Florida.

The state health department said on Twitter that the patient is a man in his 20s with no history of travel. The department said it is working with the CDC to investigate.

The variant has also been confirmed in cases in Colorado and California. It is believed to be more contagious. The BBC reported that the new variant increases the reproduction, or “R number,” by 0.4 and 0.7. The UK’s most recent R number has been estimated at 1.1-1.3, meaning anyone who has the coronavirus could be assumed to spread it to up to 1.3 people.

The R number needs to be below 1.0 for the spread of the virus to fall.

“There is a huge difference in how easily the variant virus spreads,” Professor Axel Gandy of London’s Imperial College told BBC News. “This is the most serious change in the virus since the epidemic began.”

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

With the shootings of Breonna Taylor, George Floyd, and other Black citizens setting off protests and unrest, race was at the forefront of national conversation in the United States – along with COVID-19 – over the past year.

“We’ve heard things like, ‘We’re in a post-racial society,’ but I think 2020 in particular has emphasized that we’re not,” said Gregory Johnson, MD, SFHM, chief medical officer of hospital medicine at Sound Physicians, a national physician practice. “Racism is very present in our lives, it’s very present in our world, and it is absolutely present in medicine.”

Yes, race is still an issue in the U.S. as we head into 2021, though this may have come as something of a surprise to people who do not live with racism daily.

“If you have a brain, you have bias, and that bias will likely apply to race as well,” Dr. Johnson said. “When we’re talking about institutional racism, the educational system and the media have led us to create presumptions and prejudices that we don’t necessarily recognize off the top because they’ve just been a part of the fabric of who we are as we’ve grown up.”

The term “racism” has extremely negative connotations because there’s character judgment attached to it, but to say someone is racist or racially insensitive does not equate them with being a Klansman, said Dr. Johnson. “I think we as people have to acknowledge that, yes, it’s possible for me to be racist and I might not be 100% aware of it. It’s being open to the possibility – or rather probability – that you are and then taking steps to figure out how you can address that, so you can limit it. And that requires constant self-evaluation and work,” he said.
 

Racism in the medical environment

Institutional racism is evident before students are even accepted into medical school, said Areeba Kara, MD, SFHM, associate professor of clinical medicine at Indiana University, Indianapolis, and a hospitalist at IU Health Physicians.

Mean MCAT scores are lower for applicants traditionally underrepresented in medicine (UIM) compared to the scores of well-represented groups.¹ “Lower scores are associated with lower acceptance rates into medical school,” Dr. Kara said. “These differences reflect unequal educational opportunities rooted in centuries of legal discrimination.”

Racism is apparent in both the hidden medical education curriculum and in lessons implicitly taught to students, said Ndidi Unaka, MD, MEd, associate program director of the pediatric residency training program at Cincinnati Children’s Hospital.

“These lessons inform the way in which we as physicians see our patients, each other, and how we practice,” she said. “We reinforce race-based medicine and shape clinical decision making through flawed guidelines and practices, which exacerbates health inequities. We teach that race – rather than racism – is a risk factor for poor health outcomes. Our students and trainees watch as we assume the worst of our patients from marginalized communities of color.”

Terms describing patients of color, such as “difficult,” “non-compliant,” or “frequent flyer” are thrown around and sometimes, instead of finding out why, “we view these states of being as static, root causes for poor outcomes rather than symptoms of social conditions and obstacles that impact overall health and wellbeing,” Dr. Unaka said.

Leadership opportunities

Though hospital medicine is a growing field, Dr. Kara noted that the 2020 State of Hospital Medicine Report found that only 5.5% of hospital medical group leaders were Black, and just 2.2% were Hispanic/Latino.² “I think these numbers speak for themselves,” she said.

Dr. Unaka said that the lack of UIM hospitalists and physician leaders creates fewer opportunities for “race-concordant mentorship relationships.” It also forces UIM physicians to shoulder more responsibilities – often obligations that do little to help them move forward in their careers – all in the name of diversity. And when UIM physicians are given leadership opportunities, Dr. Unaka said they are often unsure as to whether their appointments are genuine or just a hollow gesture made for the sake of diversity.

Dr. Johnson pointed out that Black and Latinx populations primarily get their care from hospital-based specialties, yet this is not reflected in the number of UIM practitioners in leadership roles. He said race and ethnicity, as well as gender, need to be factors when individuals are evaluated for leadership opportunities – for the individual’s sake, as well as for the community he or she is serving.

“When we can evaluate for unconscious bias and factor in that diverse groups tend to have better outcomes, whether it’s business or clinical outcomes, it’s one of the opportunities that we collectively have in the specialty to improve what we’re delivering for hospitals and, more importantly, for patients,” he said.
 

Relationships with colleagues and patients

Racism creeps into interactions and relationships with others as well, whether it’s between clinicians, clinician to patient, or patient to clinician. Sometimes it’s blatant; often it’s subtle.

A common, recurring example Dr. Unaka has experienced in the clinician to clinician relationship is being confused for other Black physicians, making her feel invisible. “The everyday verbal, nonverbal, and environmental slights, snubs, or insults from colleagues are frequent and contribute to feelings of exclusion, isolation, and exhaustion,” she said. Despite this, she is still expected to “address microaggressions and other forms of interpersonal racism and find ways to move through professional spaces in spite of the trauma, fear, and stress associated with my reality and lived experiences.” She said that clinicians who remain silent on the topic of racism participate in the violence and contribute to the disillusionment of UIM physicians.

Dr. Kara said that the discrimination from the health care team is the hardest to deal with. In the clinician to clinician relationship, there is a sense among UIM physicians that they’re being watched more closely and “have to prove themselves at every single turn.” Unfortunately, this comes from the environment, which tends to be adversarial rather than supportive and nurturing, she said.

“There are lots of opportunities for racism or racial insensitivity to crop up from clinician to clinician,” said Dr. Johnson. When he started his career as a physician after his training, Dr. Johnson was informed that his colleagues were watching him because they were not sure about his clinical skills. The fact that he was a former chief resident and board certified in two specialties did not seem to make any difference.

Patients refusing care from UIM physicians or expressing disapproval – both verbal and nonverbal – of such care, happens all too often. “It’s easier for me to excuse patients and their families as we often meet them on their worst days,” said Dr. Kara. Still, “understanding my oath to care for people and do no harm, but at the same time, recognizing that this is an individual that is rejecting my care without having any idea of who I am as a physician is frustrating,” Dr. Johnson acknowledged.

Then there’s the complex clinician to patient relationship, which research clearly shows contributes to health disparities.³ For one thing, the physician workforce does not reflect the patient population, Dr. Unaka said. “We cannot ignore the lack of race concordance between patients and clinicians, nor can the continued misplacement of blame for medical mistrust be at the feet of our patients,” she said.

Dr. Unaka feels that clinicians need to accept both that health inequities exist and that frontline physicians themselves contribute to the inequities. “Our diagnostic and therapeutic decisions are not immune to bias and are influenced by our deeply held beliefs about specific populations,” she said. “And the health care system that our patients navigate is no different than other systems, settings, and environments that are marred by racism in all its forms.”

Systemic racism greatly impacts patient care, said Dr. Kara. She pointed to several examples: Research showing that race concordance between patients and providers in an emergency department setting led to better pain control with fewer analgesics.⁴ The high maternal and infant mortality rates amongst Black women and children.⁵ Evidence of poorer outcomes in sepsis patients with limited English proficiency.⁶ “There are plenty more,” she said. “We need to be asking ourselves what we are going to do about it.”
 

Moving forward

That racial biases are steeped so thoroughly into our culture and consciousness means that moving beyond them is a continual, purposeful work in progress. But it is work that is critical for everyone, and certainly necessary for those who care for their fellow human beings when they are in a vulnerable state.

Health care systems need to move toward equity – giving everyone what they need to thrive – rather than focusing on equality – giving everyone the same thing, said Jenny Baenziger, MD, assistant professor of clinical medicine and pediatrics at Indiana University, Indianapolis, and associate director of education at IU Center for Global Health. “We know that minoritized patients are going to need more attention, more advocacy, more sensitivity, and more creative solutions in order to help them achieve health in a world that is often stacked against them,” she said.

References

1. Lucey CR, Saguil, A. The Consequences of Structural Racism on MCAT Scores and Medical School Admissions: The Past Is Prologue. Acad Med. 2020 Mar;95(3):351-356. doi: 10.1097/ACM.0000000000002939.

2. Flores L. Increasing racial diversity in hospital medicine’s leadership ranks. The Hospitalist. 2020 Oct 21.

3. Smedley BD, et al, eds. Unequal Treatment: Confronting Racial and Ethnic Disparities in Health Care. Institute of Medicine Committee on Understanding and Eliminating Racial and Ethnic Disparities in Health Care. Washington: National Academies Press; 2003.

4. Heins A, et al. Physician Race/Ethnicity Predicts Successful Emergency Department Analgesia. J Pain. 2010 July;11(7):692-697. doi: 10.1016/j.jpain.2009.10.017.

5. U.S. Department of Health and Human Serves, Office of Minority Health. Infant Mortality and African Americans. 2019 Nov 8. minorityhealth.hhs.gov/omh/browse.aspx?lvl=4&lvlid=23.

6. Jacobs ZG, et al. The Association between Limited English Proficiency and Sepsis Mortality. J Hosp Med. 2020;3;140-146. Published Online First 2019 Nov 20. doi:10.12788/jhm.3334.

7. Finucane TE. Mention of a Patient’s “Race” in Clinical Presentations. Virtual Mentor. 2014;16(6):423-427. doi: 10.1001/virtualmentor.2014.16.6.ecas1-1406.

With the shootings of Breonna Taylor, George Floyd, and other Black citizens setting off protests and unrest, race was at the forefront of national conversation in the United States – along with COVID-19 – over the past year.

“We’ve heard things like, ‘We’re in a post-racial society,’ but I think 2020 in particular has emphasized that we’re not,” said Gregory Johnson, MD, SFHM, chief medical officer of hospital medicine at Sound Physicians, a national physician practice. “Racism is very present in our lives, it’s very present in our world, and it is absolutely present in medicine.”

Yes, race is still an issue in the U.S. as we head into 2021, though this may have come as something of a surprise to people who do not live with racism daily.

“If you have a brain, you have bias, and that bias will likely apply to race as well,” Dr. Johnson said. “When we’re talking about institutional racism, the educational system and the media have led us to create presumptions and prejudices that we don’t necessarily recognize off the top because they’ve just been a part of the fabric of who we are as we’ve grown up.”

The term “racism” has extremely negative connotations because there’s character judgment attached to it, but to say someone is racist or racially insensitive does not equate them with being a Klansman, said Dr. Johnson. “I think we as people have to acknowledge that, yes, it’s possible for me to be racist and I might not be 100% aware of it. It’s being open to the possibility – or rather probability – that you are and then taking steps to figure out how you can address that, so you can limit it. And that requires constant self-evaluation and work,” he said.
 

Racism in the medical environment

Institutional racism is evident before students are even accepted into medical school, said Areeba Kara, MD, SFHM, associate professor of clinical medicine at Indiana University, Indianapolis, and a hospitalist at IU Health Physicians.

Mean MCAT scores are lower for applicants traditionally underrepresented in medicine (UIM) compared to the scores of well-represented groups.¹ “Lower scores are associated with lower acceptance rates into medical school,” Dr. Kara said. “These differences reflect unequal educational opportunities rooted in centuries of legal discrimination.”

Racism is apparent in both the hidden medical education curriculum and in lessons implicitly taught to students, said Ndidi Unaka, MD, MEd, associate program director of the pediatric residency training program at Cincinnati Children’s Hospital.

“These lessons inform the way in which we as physicians see our patients, each other, and how we practice,” she said. “We reinforce race-based medicine and shape clinical decision making through flawed guidelines and practices, which exacerbates health inequities. We teach that race – rather than racism – is a risk factor for poor health outcomes. Our students and trainees watch as we assume the worst of our patients from marginalized communities of color.”

Terms describing patients of color, such as “difficult,” “non-compliant,” or “frequent flyer” are thrown around and sometimes, instead of finding out why, “we view these states of being as static, root causes for poor outcomes rather than symptoms of social conditions and obstacles that impact overall health and wellbeing,” Dr. Unaka said.

Leadership opportunities

Though hospital medicine is a growing field, Dr. Kara noted that the 2020 State of Hospital Medicine Report found that only 5.5% of hospital medical group leaders were Black, and just 2.2% were Hispanic/Latino.² “I think these numbers speak for themselves,” she said.

Dr. Unaka said that the lack of UIM hospitalists and physician leaders creates fewer opportunities for “race-concordant mentorship relationships.” It also forces UIM physicians to shoulder more responsibilities – often obligations that do little to help them move forward in their careers – all in the name of diversity. And when UIM physicians are given leadership opportunities, Dr. Unaka said they are often unsure as to whether their appointments are genuine or just a hollow gesture made for the sake of diversity.

Dr. Johnson pointed out that Black and Latinx populations primarily get their care from hospital-based specialties, yet this is not reflected in the number of UIM practitioners in leadership roles. He said race and ethnicity, as well as gender, need to be factors when individuals are evaluated for leadership opportunities – for the individual’s sake, as well as for the community he or she is serving.

“When we can evaluate for unconscious bias and factor in that diverse groups tend to have better outcomes, whether it’s business or clinical outcomes, it’s one of the opportunities that we collectively have in the specialty to improve what we’re delivering for hospitals and, more importantly, for patients,” he said.
 

Relationships with colleagues and patients

Racism creeps into interactions and relationships with others as well, whether it’s between clinicians, clinician to patient, or patient to clinician. Sometimes it’s blatant; often it’s subtle.

A common, recurring example Dr. Unaka has experienced in the clinician to clinician relationship is being confused for other Black physicians, making her feel invisible. “The everyday verbal, nonverbal, and environmental slights, snubs, or insults from colleagues are frequent and contribute to feelings of exclusion, isolation, and exhaustion,” she said. Despite this, she is still expected to “address microaggressions and other forms of interpersonal racism and find ways to move through professional spaces in spite of the trauma, fear, and stress associated with my reality and lived experiences.” She said that clinicians who remain silent on the topic of racism participate in the violence and contribute to the disillusionment of UIM physicians.

Dr. Kara said that the discrimination from the health care team is the hardest to deal with. In the clinician to clinician relationship, there is a sense among UIM physicians that they’re being watched more closely and “have to prove themselves at every single turn.” Unfortunately, this comes from the environment, which tends to be adversarial rather than supportive and nurturing, she said.

“There are lots of opportunities for racism or racial insensitivity to crop up from clinician to clinician,” said Dr. Johnson. When he started his career as a physician after his training, Dr. Johnson was informed that his colleagues were watching him because they were not sure about his clinical skills. The fact that he was a former chief resident and board certified in two specialties did not seem to make any difference.

Patients refusing care from UIM physicians or expressing disapproval – both verbal and nonverbal – of such care, happens all too often. “It’s easier for me to excuse patients and their families as we often meet them on their worst days,” said Dr. Kara. Still, “understanding my oath to care for people and do no harm, but at the same time, recognizing that this is an individual that is rejecting my care without having any idea of who I am as a physician is frustrating,” Dr. Johnson acknowledged.

Then there’s the complex clinician to patient relationship, which research clearly shows contributes to health disparities.³ For one thing, the physician workforce does not reflect the patient population, Dr. Unaka said. “We cannot ignore the lack of race concordance between patients and clinicians, nor can the continued misplacement of blame for medical mistrust be at the feet of our patients,” she said.

Dr. Unaka feels that clinicians need to accept both that health inequities exist and that frontline physicians themselves contribute to the inequities. “Our diagnostic and therapeutic decisions are not immune to bias and are influenced by our deeply held beliefs about specific populations,” she said. “And the health care system that our patients navigate is no different than other systems, settings, and environments that are marred by racism in all its forms.”

Systemic racism greatly impacts patient care, said Dr. Kara. She pointed to several examples: Research showing that race concordance between patients and providers in an emergency department setting led to better pain control with fewer analgesics.⁴ The high maternal and infant mortality rates amongst Black women and children.⁵ Evidence of poorer outcomes in sepsis patients with limited English proficiency.⁶ “There are plenty more,” she said. “We need to be asking ourselves what we are going to do about it.”
 

Moving forward

That racial biases are steeped so thoroughly into our culture and consciousness means that moving beyond them is a continual, purposeful work in progress. But it is work that is critical for everyone, and certainly necessary for those who care for their fellow human beings when they are in a vulnerable state.

Health care systems need to move toward equity – giving everyone what they need to thrive – rather than focusing on equality – giving everyone the same thing, said Jenny Baenziger, MD, assistant professor of clinical medicine and pediatrics at Indiana University, Indianapolis, and associate director of education at IU Center for Global Health. “We know that minoritized patients are going to need more attention, more advocacy, more sensitivity, and more creative solutions in order to help them achieve health in a world that is often stacked against them,” she said.

References

1. Lucey CR, Saguil, A. The Consequences of Structural Racism on MCAT Scores and Medical School Admissions: The Past Is Prologue. Acad Med. 2020 Mar;95(3):351-356. doi: 10.1097/ACM.0000000000002939.

2. Flores L. Increasing racial diversity in hospital medicine’s leadership ranks. The Hospitalist. 2020 Oct 21.

3. Smedley BD, et al, eds. Unequal Treatment: Confronting Racial and Ethnic Disparities in Health Care. Institute of Medicine Committee on Understanding and Eliminating Racial and Ethnic Disparities in Health Care. Washington: National Academies Press; 2003.

4. Heins A, et al. Physician Race/Ethnicity Predicts Successful Emergency Department Analgesia. J Pain. 2010 July;11(7):692-697. doi: 10.1016/j.jpain.2009.10.017.

5. U.S. Department of Health and Human Serves, Office of Minority Health. Infant Mortality and African Americans. 2019 Nov 8. minorityhealth.hhs.gov/omh/browse.aspx?lvl=4&lvlid=23.

6. Jacobs ZG, et al. The Association between Limited English Proficiency and Sepsis Mortality. J Hosp Med. 2020;3;140-146. Published Online First 2019 Nov 20. doi:10.12788/jhm.3334.

7. Finucane TE. Mention of a Patient’s “Race” in Clinical Presentations. Virtual Mentor. 2014;16(6):423-427. doi: 10.1001/virtualmentor.2014.16.6.ecas1-1406.

With the shootings of Breonna Taylor, George Floyd, and other Black citizens setting off protests and unrest, race was at the forefront of national conversation in the United States – along with COVID-19 – over the past year.

“We’ve heard things like, ‘We’re in a post-racial society,’ but I think 2020 in particular has emphasized that we’re not,” said Gregory Johnson, MD, SFHM, chief medical officer of hospital medicine at Sound Physicians, a national physician practice. “Racism is very present in our lives, it’s very present in our world, and it is absolutely present in medicine.”

Yes, race is still an issue in the U.S. as we head into 2021, though this may have come as something of a surprise to people who do not live with racism daily.

“If you have a brain, you have bias, and that bias will likely apply to race as well,” Dr. Johnson said. “When we’re talking about institutional racism, the educational system and the media have led us to create presumptions and prejudices that we don’t necessarily recognize off the top because they’ve just been a part of the fabric of who we are as we’ve grown up.”

The term “racism” has extremely negative connotations because there’s character judgment attached to it, but to say someone is racist or racially insensitive does not equate them with being a Klansman, said Dr. Johnson. “I think we as people have to acknowledge that, yes, it’s possible for me to be racist and I might not be 100% aware of it. It’s being open to the possibility – or rather probability – that you are and then taking steps to figure out how you can address that, so you can limit it. And that requires constant self-evaluation and work,” he said.
 

Racism in the medical environment

Institutional racism is evident before students are even accepted into medical school, said Areeba Kara, MD, SFHM, associate professor of clinical medicine at Indiana University, Indianapolis, and a hospitalist at IU Health Physicians.

Mean MCAT scores are lower for applicants traditionally underrepresented in medicine (UIM) compared to the scores of well-represented groups.¹ “Lower scores are associated with lower acceptance rates into medical school,” Dr. Kara said. “These differences reflect unequal educational opportunities rooted in centuries of legal discrimination.”

Racism is apparent in both the hidden medical education curriculum and in lessons implicitly taught to students, said Ndidi Unaka, MD, MEd, associate program director of the pediatric residency training program at Cincinnati Children’s Hospital.

“These lessons inform the way in which we as physicians see our patients, each other, and how we practice,” she said. “We reinforce race-based medicine and shape clinical decision making through flawed guidelines and practices, which exacerbates health inequities. We teach that race – rather than racism – is a risk factor for poor health outcomes. Our students and trainees watch as we assume the worst of our patients from marginalized communities of color.”

Terms describing patients of color, such as “difficult,” “non-compliant,” or “frequent flyer” are thrown around and sometimes, instead of finding out why, “we view these states of being as static, root causes for poor outcomes rather than symptoms of social conditions and obstacles that impact overall health and wellbeing,” Dr. Unaka said.

Leadership opportunities

Though hospital medicine is a growing field, Dr. Kara noted that the 2020 State of Hospital Medicine Report found that only 5.5% of hospital medical group leaders were Black, and just 2.2% were Hispanic/Latino.² “I think these numbers speak for themselves,” she said.

Dr. Unaka said that the lack of UIM hospitalists and physician leaders creates fewer opportunities for “race-concordant mentorship relationships.” It also forces UIM physicians to shoulder more responsibilities – often obligations that do little to help them move forward in their careers – all in the name of diversity. And when UIM physicians are given leadership opportunities, Dr. Unaka said they are often unsure as to whether their appointments are genuine or just a hollow gesture made for the sake of diversity.

Dr. Johnson pointed out that Black and Latinx populations primarily get their care from hospital-based specialties, yet this is not reflected in the number of UIM practitioners in leadership roles. He said race and ethnicity, as well as gender, need to be factors when individuals are evaluated for leadership opportunities – for the individual’s sake, as well as for the community he or she is serving.

“When we can evaluate for unconscious bias and factor in that diverse groups tend to have better outcomes, whether it’s business or clinical outcomes, it’s one of the opportunities that we collectively have in the specialty to improve what we’re delivering for hospitals and, more importantly, for patients,” he said.
 

Relationships with colleagues and patients

Racism creeps into interactions and relationships with others as well, whether it’s between clinicians, clinician to patient, or patient to clinician. Sometimes it’s blatant; often it’s subtle.

A common, recurring example Dr. Unaka has experienced in the clinician to clinician relationship is being confused for other Black physicians, making her feel invisible. “The everyday verbal, nonverbal, and environmental slights, snubs, or insults from colleagues are frequent and contribute to feelings of exclusion, isolation, and exhaustion,” she said. Despite this, she is still expected to “address microaggressions and other forms of interpersonal racism and find ways to move through professional spaces in spite of the trauma, fear, and stress associated with my reality and lived experiences.” She said that clinicians who remain silent on the topic of racism participate in the violence and contribute to the disillusionment of UIM physicians.

Dr. Kara said that the discrimination from the health care team is the hardest to deal with. In the clinician to clinician relationship, there is a sense among UIM physicians that they’re being watched more closely and “have to prove themselves at every single turn.” Unfortunately, this comes from the environment, which tends to be adversarial rather than supportive and nurturing, she said.

“There are lots of opportunities for racism or racial insensitivity to crop up from clinician to clinician,” said Dr. Johnson. When he started his career as a physician after his training, Dr. Johnson was informed that his colleagues were watching him because they were not sure about his clinical skills. The fact that he was a former chief resident and board certified in two specialties did not seem to make any difference.

Patients refusing care from UIM physicians or expressing disapproval – both verbal and nonverbal – of such care, happens all too often. “It’s easier for me to excuse patients and their families as we often meet them on their worst days,” said Dr. Kara. Still, “understanding my oath to care for people and do no harm, but at the same time, recognizing that this is an individual that is rejecting my care without having any idea of who I am as a physician is frustrating,” Dr. Johnson acknowledged.

Then there’s the complex clinician to patient relationship, which research clearly shows contributes to health disparities.³ For one thing, the physician workforce does not reflect the patient population, Dr. Unaka said. “We cannot ignore the lack of race concordance between patients and clinicians, nor can the continued misplacement of blame for medical mistrust be at the feet of our patients,” she said.

Dr. Unaka feels that clinicians need to accept both that health inequities exist and that frontline physicians themselves contribute to the inequities. “Our diagnostic and therapeutic decisions are not immune to bias and are influenced by our deeply held beliefs about specific populations,” she said. “And the health care system that our patients navigate is no different than other systems, settings, and environments that are marred by racism in all its forms.”

Systemic racism greatly impacts patient care, said Dr. Kara. She pointed to several examples: Research showing that race concordance between patients and providers in an emergency department setting led to better pain control with fewer analgesics.⁴ The high maternal and infant mortality rates amongst Black women and children.⁵ Evidence of poorer outcomes in sepsis patients with limited English proficiency.⁶ “There are plenty more,” she said. “We need to be asking ourselves what we are going to do about it.”
 

Moving forward

That racial biases are steeped so thoroughly into our culture and consciousness means that moving beyond them is a continual, purposeful work in progress. But it is work that is critical for everyone, and certainly necessary for those who care for their fellow human beings when they are in a vulnerable state.

Health care systems need to move toward equity – giving everyone what they need to thrive – rather than focusing on equality – giving everyone the same thing, said Jenny Baenziger, MD, assistant professor of clinical medicine and pediatrics at Indiana University, Indianapolis, and associate director of education at IU Center for Global Health. “We know that minoritized patients are going to need more attention, more advocacy, more sensitivity, and more creative solutions in order to help them achieve health in a world that is often stacked against them,” she said.

References

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