Fecal microbiota transplantation (FMT) appears safe and effective as a treatment for most Clostridioides difficile infections as it is currently being administered, researchers say.

“We actually didn’t see any infections that were definitely transmissible via fecal transplant,” Colleen Kelly, MD, an associate professor of medicine at Brown University, Providence, R.I., said in an interview.

The findings, published online Oct. 1 in the journal Gastroenterology, come from the American Gastroenterological Association (AGA) NIH-funded FMT National Registry and could allay concerns about a treatment that has yet to gain full approval by the Food and Drug Administration, despite successful clinical trials.

C. diff infections are common and increasing in the United States, often can’t be cured with conventional treatments such as antibiotics, and can be deadly.

Transplanting fecal matter from a donor to the patient appears to work by restoring beneficial microorganisms to the patient’s gut. The procedure is also under investigation for a wide range of other ailments, from irritable bowel syndrome to mood disorders.

But much remains unknown. Researchers have counted a thousand bacterial species along with viruses, bacteriophages, archaea, and fungi in the human gut that interact in complex ways, not all of them beneficial.

The FDA has not enforced regulations that would prohibit the procedure, but in March, it warned about infections with enteropathogenic Escherichia coli and Shiga toxin–producing E. coli following fecal transplants.

As a result of these reports, and the theoretical risk of spreading SARS-CoV-2, OpenBiome, the largest stool bank in the United States, has suspended shipments except for emergency orders, and asked clinicians to quarantine any of its products they already have on hand.

In the meantime, long-term effects of the treatment have not been well documented. And clinical trials have excluded patients who might benefit, such as those who have been immunocompromised or have inflammatory bowel disease.
 

National registry follows patients outside clinical trials

To better understand how patients fare outside these trials, AGA and other organizations developed a national registry, funded by a grant from the National Institute of Allergy and Infectious Diseases.

The current report summarizes results on 259 patients enrolled between Dec. 5, 2017, and Sept. 2, 2019 at 20 sites.

At baseline, 44% of these patients suffered moderate and 36% mild C. diff infections. The duration of the diagnosis ranged from less than 1 week to 9 years, with a median duration of 20 weeks. They ranged from 1 to 15 episodes with a mean of 3.5.

Almost all had received vancomycin, and 62% had at least two courses. About 40% had received metronidazole and 28% had received fidaxomicin.

Almost all participants received stool from an unknown donor, mostly from stool banks, with OpenBiome accounting for 67%. About 85% of the transplants were administered through colonoscopy and 6% by upper endoscopy.

Out of 222 patients who returned for a 1-month follow-up, 90% met the investigators’ definition of cure: resolution of diarrhea without need for further anti–C. diff therapy. About 98% received only one transplant. An intent to treat analysis produced a cure rate of 86%.

Results were good in patients with comorbidities, including 12% who had irritable bowel syndrome, 9% who had ulcerative colitis, and 7% who had Crohn’s disease, Dr. Kelly said. “I hope everybody sees the importance of it. In these patients that are more complicated, who may have underlying comorbidities, who may not have been in the clinical trials, it looks effective in that group, and also incredibly safe.”

She added that the risk of transmitting SARS-CoV-2 is minor. “I think it would be a very, very unlikely way for someone to get a respiratory pathogen.”

Of the 112 participants who were cured at 1 month and returned for follow-up after 6 months, 4 developed recurrent C. diff infection. Eleven patients who were not cured in the first month returned after 6 months. Of these, seven were reported cured at this later follow-up.

Three complications occurred as result of the procedure: one colonoscopic perforation and two episodes of gastrointestinal bleeding.

About 45% of participants reported at least one symptom, with diarrhea not related to C. difficile the most common, followed by abdominal pain, bloating, and constipation.

Eleven patients suffered infections, including two which the investigators thought might be related to the procedure: Bacteroides fragilis in one participant with severe diarrhea, and enteropathogenic E. coli in another with loose stools. Other infections included four urinary tract infections, three cases of pneumonia, one E. coli bacteremia and one tooth infection.

Within a month of the procedure, 27 patients were hospitalized, with 3 of these cases considered possibly related to the procedure.
 

Findings may not apply to all clinical settings

Vincent B. Young, MD, PhD, a professor of medicine and infectious diseases at the University of Michigan, Ann Arbor, pointed out that the findings might not apply to all clinical settings. The participating clinicians were almost all gastroenterologists working in academic centers.

“Most of them are not Joe Doctor at the doctor’s office,” said Dr. Young, who was not involved with the study. Clinicians in other specialties, such as infectious diseases, might be more inclined to administer fecal transplants through capsules rather than colonoscopies.

And he added that the study does not address effects of the transplant that might develop over years. “Some people talk about how changes in the microbiota lead to increased risk for long-term complications, things like cancer or heart disease. You’re not going to see those in 6 months.”

Also, the study didn’t yield any findings on indications other than C. diff. “In no way, shape, or form does it mean you can use it for autism, depression, heart disease, or [irritable bowel syndrome],” he said.

Still, he said, the study “confirms the fact that fecal cell transplantation is an effective treatment for recurrent C. diff infection when administered as they administered it.”

The National Institute of Allergy and Infectious Diseases funded the registry. Dr. Kelly reported a relationship with Finch Therapeutics. Dr. Young reports financial relationships with Vedanta Biosciences and Bio-K+.

This story was updated on Oct. 4, 2020.

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

Fecal microbiota transplantation (FMT) appears safe and effective as a treatment for most Clostridioides difficile infections as it is currently being administered, researchers say.

“We actually didn’t see any infections that were definitely transmissible via fecal transplant,” Colleen Kelly, MD, an associate professor of medicine at Brown University, Providence, R.I., said in an interview.

The findings, published online Oct. 1 in the journal Gastroenterology, come from the American Gastroenterological Association (AGA) NIH-funded FMT National Registry and could allay concerns about a treatment that has yet to gain full approval by the Food and Drug Administration, despite successful clinical trials.

C. diff infections are common and increasing in the United States, often can’t be cured with conventional treatments such as antibiotics, and can be deadly.

Transplanting fecal matter from a donor to the patient appears to work by restoring beneficial microorganisms to the patient’s gut. The procedure is also under investigation for a wide range of other ailments, from irritable bowel syndrome to mood disorders.

But much remains unknown. Researchers have counted a thousand bacterial species along with viruses, bacteriophages, archaea, and fungi in the human gut that interact in complex ways, not all of them beneficial.

The FDA has not enforced regulations that would prohibit the procedure, but in March, it warned about infections with enteropathogenic Escherichia coli and Shiga toxin–producing E. coli following fecal transplants.

As a result of these reports, and the theoretical risk of spreading SARS-CoV-2, OpenBiome, the largest stool bank in the United States, has suspended shipments except for emergency orders, and asked clinicians to quarantine any of its products they already have on hand.

In the meantime, long-term effects of the treatment have not been well documented. And clinical trials have excluded patients who might benefit, such as those who have been immunocompromised or have inflammatory bowel disease.
 

National registry follows patients outside clinical trials

To better understand how patients fare outside these trials, AGA and other organizations developed a national registry, funded by a grant from the National Institute of Allergy and Infectious Diseases.

The current report summarizes results on 259 patients enrolled between Dec. 5, 2017, and Sept. 2, 2019 at 20 sites.

At baseline, 44% of these patients suffered moderate and 36% mild C. diff infections. The duration of the diagnosis ranged from less than 1 week to 9 years, with a median duration of 20 weeks. They ranged from 1 to 15 episodes with a mean of 3.5.

Almost all had received vancomycin, and 62% had at least two courses. About 40% had received metronidazole and 28% had received fidaxomicin.

Almost all participants received stool from an unknown donor, mostly from stool banks, with OpenBiome accounting for 67%. About 85% of the transplants were administered through colonoscopy and 6% by upper endoscopy.

Out of 222 patients who returned for a 1-month follow-up, 90% met the investigators’ definition of cure: resolution of diarrhea without need for further anti–C. diff therapy. About 98% received only one transplant. An intent to treat analysis produced a cure rate of 86%.

Results were good in patients with comorbidities, including 12% who had irritable bowel syndrome, 9% who had ulcerative colitis, and 7% who had Crohn’s disease, Dr. Kelly said. “I hope everybody sees the importance of it. In these patients that are more complicated, who may have underlying comorbidities, who may not have been in the clinical trials, it looks effective in that group, and also incredibly safe.”

She added that the risk of transmitting SARS-CoV-2 is minor. “I think it would be a very, very unlikely way for someone to get a respiratory pathogen.”

Of the 112 participants who were cured at 1 month and returned for follow-up after 6 months, 4 developed recurrent C. diff infection. Eleven patients who were not cured in the first month returned after 6 months. Of these, seven were reported cured at this later follow-up.

Three complications occurred as result of the procedure: one colonoscopic perforation and two episodes of gastrointestinal bleeding.

About 45% of participants reported at least one symptom, with diarrhea not related to C. difficile the most common, followed by abdominal pain, bloating, and constipation.

Eleven patients suffered infections, including two which the investigators thought might be related to the procedure: Bacteroides fragilis in one participant with severe diarrhea, and enteropathogenic E. coli in another with loose stools. Other infections included four urinary tract infections, three cases of pneumonia, one E. coli bacteremia and one tooth infection.

Within a month of the procedure, 27 patients were hospitalized, with 3 of these cases considered possibly related to the procedure.
 

Findings may not apply to all clinical settings

Vincent B. Young, MD, PhD, a professor of medicine and infectious diseases at the University of Michigan, Ann Arbor, pointed out that the findings might not apply to all clinical settings. The participating clinicians were almost all gastroenterologists working in academic centers.

“Most of them are not Joe Doctor at the doctor’s office,” said Dr. Young, who was not involved with the study. Clinicians in other specialties, such as infectious diseases, might be more inclined to administer fecal transplants through capsules rather than colonoscopies.

And he added that the study does not address effects of the transplant that might develop over years. “Some people talk about how changes in the microbiota lead to increased risk for long-term complications, things like cancer or heart disease. You’re not going to see those in 6 months.”

Also, the study didn’t yield any findings on indications other than C. diff. “In no way, shape, or form does it mean you can use it for autism, depression, heart disease, or [irritable bowel syndrome],” he said.

Still, he said, the study “confirms the fact that fecal cell transplantation is an effective treatment for recurrent C. diff infection when administered as they administered it.”

The National Institute of Allergy and Infectious Diseases funded the registry. Dr. Kelly reported a relationship with Finch Therapeutics. Dr. Young reports financial relationships with Vedanta Biosciences and Bio-K+.

This story was updated on Oct. 4, 2020.

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

Fecal microbiota transplantation (FMT) appears safe and effective as a treatment for most Clostridioides difficile infections as it is currently being administered, researchers say.

“We actually didn’t see any infections that were definitely transmissible via fecal transplant,” Colleen Kelly, MD, an associate professor of medicine at Brown University, Providence, R.I., said in an interview.

The findings, published online Oct. 1 in the journal Gastroenterology, come from the American Gastroenterological Association (AGA) NIH-funded FMT National Registry and could allay concerns about a treatment that has yet to gain full approval by the Food and Drug Administration, despite successful clinical trials.

C. diff infections are common and increasing in the United States, often can’t be cured with conventional treatments such as antibiotics, and can be deadly.

Transplanting fecal matter from a donor to the patient appears to work by restoring beneficial microorganisms to the patient’s gut. The procedure is also under investigation for a wide range of other ailments, from irritable bowel syndrome to mood disorders.

But much remains unknown. Researchers have counted a thousand bacterial species along with viruses, bacteriophages, archaea, and fungi in the human gut that interact in complex ways, not all of them beneficial.

The FDA has not enforced regulations that would prohibit the procedure, but in March, it warned about infections with enteropathogenic Escherichia coli and Shiga toxin–producing E. coli following fecal transplants.

As a result of these reports, and the theoretical risk of spreading SARS-CoV-2, OpenBiome, the largest stool bank in the United States, has suspended shipments except for emergency orders, and asked clinicians to quarantine any of its products they already have on hand.

In the meantime, long-term effects of the treatment have not been well documented. And clinical trials have excluded patients who might benefit, such as those who have been immunocompromised or have inflammatory bowel disease.
 

National registry follows patients outside clinical trials

To better understand how patients fare outside these trials, AGA and other organizations developed a national registry, funded by a grant from the National Institute of Allergy and Infectious Diseases.

The current report summarizes results on 259 patients enrolled between Dec. 5, 2017, and Sept. 2, 2019 at 20 sites.

At baseline, 44% of these patients suffered moderate and 36% mild C. diff infections. The duration of the diagnosis ranged from less than 1 week to 9 years, with a median duration of 20 weeks. They ranged from 1 to 15 episodes with a mean of 3.5.

Almost all had received vancomycin, and 62% had at least two courses. About 40% had received metronidazole and 28% had received fidaxomicin.

Almost all participants received stool from an unknown donor, mostly from stool banks, with OpenBiome accounting for 67%. About 85% of the transplants were administered through colonoscopy and 6% by upper endoscopy.

Out of 222 patients who returned for a 1-month follow-up, 90% met the investigators’ definition of cure: resolution of diarrhea without need for further anti–C. diff therapy. About 98% received only one transplant. An intent to treat analysis produced a cure rate of 86%.

Results were good in patients with comorbidities, including 12% who had irritable bowel syndrome, 9% who had ulcerative colitis, and 7% who had Crohn’s disease, Dr. Kelly said. “I hope everybody sees the importance of it. In these patients that are more complicated, who may have underlying comorbidities, who may not have been in the clinical trials, it looks effective in that group, and also incredibly safe.”

She added that the risk of transmitting SARS-CoV-2 is minor. “I think it would be a very, very unlikely way for someone to get a respiratory pathogen.”

Of the 112 participants who were cured at 1 month and returned for follow-up after 6 months, 4 developed recurrent C. diff infection. Eleven patients who were not cured in the first month returned after 6 months. Of these, seven were reported cured at this later follow-up.

Three complications occurred as result of the procedure: one colonoscopic perforation and two episodes of gastrointestinal bleeding.

About 45% of participants reported at least one symptom, with diarrhea not related to C. difficile the most common, followed by abdominal pain, bloating, and constipation.

Eleven patients suffered infections, including two which the investigators thought might be related to the procedure: Bacteroides fragilis in one participant with severe diarrhea, and enteropathogenic E. coli in another with loose stools. Other infections included four urinary tract infections, three cases of pneumonia, one E. coli bacteremia and one tooth infection.

Within a month of the procedure, 27 patients were hospitalized, with 3 of these cases considered possibly related to the procedure.
 

Findings may not apply to all clinical settings

Vincent B. Young, MD, PhD, a professor of medicine and infectious diseases at the University of Michigan, Ann Arbor, pointed out that the findings might not apply to all clinical settings. The participating clinicians were almost all gastroenterologists working in academic centers.

“Most of them are not Joe Doctor at the doctor’s office,” said Dr. Young, who was not involved with the study. Clinicians in other specialties, such as infectious diseases, might be more inclined to administer fecal transplants through capsules rather than colonoscopies.

And he added that the study does not address effects of the transplant that might develop over years. “Some people talk about how changes in the microbiota lead to increased risk for long-term complications, things like cancer or heart disease. You’re not going to see those in 6 months.”

Also, the study didn’t yield any findings on indications other than C. diff. “In no way, shape, or form does it mean you can use it for autism, depression, heart disease, or [irritable bowel syndrome],” he said.

Still, he said, the study “confirms the fact that fecal cell transplantation is an effective treatment for recurrent C. diff infection when administered as they administered it.”

The National Institute of Allergy and Infectious Diseases funded the registry. Dr. Kelly reported a relationship with Finch Therapeutics. Dr. Young reports financial relationships with Vedanta Biosciences and Bio-K+.

This story was updated on Oct. 4, 2020.

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

A psychiatric diagnosis for patients hospitalized with COVID-19 is linked to a significantly increased risk for death, new research shows.

Investigators found that patients who were hospitalized with COVID-19 and who had been diagnosed with a psychiatric disorder had a 50% increased risk for a COVID-related death in comparison with COVID-19 patients who had not received a psychiatric diagnosis.

“Pay attention and potentially address/treat a prior psychiatric diagnosis if a patient is hospitalized for COVID-19, as this risk factor can impact the patient’s outcome – death – while in the hospital,” lead investigator Luming Li, MD, assistant professor of psychiatry and associate medical director of quality improvement, Yale New Haven Psychiatric Hospital, New Haven, Conn., said in an interview.

The study was published Sept. 30 in JAMA Network Open.
 

Negative impact

“We were interested to learn more about the impact of psychiatric diagnoses on COVID-19 mortality, as prior large cohort studies included neurological and other medical conditions but did not assess for a priori psychiatric diagnoses,” said Dr. Li.

“We know from the literature that prior psychiatric diagnoses can have a negative impact on the outcomes of medical conditions, and therefore we tested our hypothesis on a cohort of patients who were hospitalized with COVID-19,” she added.

To investigate, the researchers analyzed data on 1,685 patients hospitalized with COVID-19 between Feb. 15 and April 25, 2020, and whose cases were followed to May 27, 2020. The patients (mean age, 65.2 years; 52.6% men) were drawn from the Yale New Haven Health System.

The median follow-up period was 8 days (interquartile range, 4-16 days) .

Of these patients, 28% had received a psychiatric diagnosis prior to hospitalization. The patients with psychiatric disorders were significantly older and were more likely to be women, White, non-Hispanic, and to have medical comorbidities (i.e., cancer, cerebrovascular disease, heart failure, diabetes, kidney disease, liver disease, MI, and/or HIV).

Psychiatric diagnoses were defined in accordance with ICD codes that included mental and behavioral health, Alzheimer’s disease, and self-injury.
 

Vulnerability to stress

In the unadjusted model, the risk for COVID-19–related hospital death was greater for those who had received any psychiatric diagnosis, compared with those had not (hazard ratio, 2.3; 95% CI, 1.8-2.9; P < .001).

In the adjusted model that controlled for demographic characteristics, other medical comorbidities, and hospital location, the mortality risk somewhat decreased but still remained significantly higher (HR, 1.5; 95% CI, 1.1-1.9; P = .003).

Dr. Li noted a number of factors that might account for the higher mortality rate among psychiatric patients who had COVID-19 in comparison with COVD-19 patients who did not have a psychiatric disorder. These included “potential inflammatory and stress responses that the body experiences related to prior psychiatric conditions,” she said.

Having been previously diagnosed with a psychiatric disorder may also “reflect existing neurochemical differences, compared to those who do not have a prior psychiatric diagnosis, [and] these differences may make the population with the prior psychiatric diagnosis more vulnerable to respond to an acute stressor such as COVID-19,” she said.
 

Quality care

Harold Pincus, MD, professor and vice chair of the department of psychiatry at Columbia University, New York, said it “adds to the fairly well-known and well-established phenomenon that people with mental illnesses have a high risk of all sorts of morbidity and mortality for non–mental health conditions.”

The researchers “adjusted for various expected [mortality] risks that would be independent of the presence of COVID-19,” so “there was something else going on associated with mortality,” said Dr. Pincus, who is also codirector of the Irving Institute for Clinical and Translation Research. He was not involved with the study.

Beyond the possibility of “some basic immunologic process affected by the presence of a mental disorder,” it is possible that the vulnerability is “related to access to quality care for the comorbid general condition that is not being effectively treated,” he said.

“The take-home message is that people with mental disorders are at higher risk for death, and we need to make sure that, irrespective of COVID-19, they get adequate preventive and chronic-disease care, which would be the most effective way to intervene and protect the impact of a serious disease like COVID-19,” he noted. This would include being appropriately vaccinated and receiving preventive healthcare to reduce smoking and encourage weight loss.

No source of funding for the study was provided. Dr. Li reported receiving grants from a Health and Aging Policy Fellowship during the conduct of the study. Dr. Pincus reported no relevant financial relationships.

A psychiatric diagnosis for patients hospitalized with COVID-19 is linked to a significantly increased risk for death, new research shows.

Investigators found that patients who were hospitalized with COVID-19 and who had been diagnosed with a psychiatric disorder had a 50% increased risk for a COVID-related death in comparison with COVID-19 patients who had not received a psychiatric diagnosis.

“Pay attention and potentially address/treat a prior psychiatric diagnosis if a patient is hospitalized for COVID-19, as this risk factor can impact the patient’s outcome – death – while in the hospital,” lead investigator Luming Li, MD, assistant professor of psychiatry and associate medical director of quality improvement, Yale New Haven Psychiatric Hospital, New Haven, Conn., said in an interview.

The study was published Sept. 30 in JAMA Network Open.
 

Negative impact

“We were interested to learn more about the impact of psychiatric diagnoses on COVID-19 mortality, as prior large cohort studies included neurological and other medical conditions but did not assess for a priori psychiatric diagnoses,” said Dr. Li.

“We know from the literature that prior psychiatric diagnoses can have a negative impact on the outcomes of medical conditions, and therefore we tested our hypothesis on a cohort of patients who were hospitalized with COVID-19,” she added.

To investigate, the researchers analyzed data on 1,685 patients hospitalized with COVID-19 between Feb. 15 and April 25, 2020, and whose cases were followed to May 27, 2020. The patients (mean age, 65.2 years; 52.6% men) were drawn from the Yale New Haven Health System.

The median follow-up period was 8 days (interquartile range, 4-16 days) .

Of these patients, 28% had received a psychiatric diagnosis prior to hospitalization. The patients with psychiatric disorders were significantly older and were more likely to be women, White, non-Hispanic, and to have medical comorbidities (i.e., cancer, cerebrovascular disease, heart failure, diabetes, kidney disease, liver disease, MI, and/or HIV).

Psychiatric diagnoses were defined in accordance with ICD codes that included mental and behavioral health, Alzheimer’s disease, and self-injury.
 

Vulnerability to stress

In the unadjusted model, the risk for COVID-19–related hospital death was greater for those who had received any psychiatric diagnosis, compared with those had not (hazard ratio, 2.3; 95% CI, 1.8-2.9; P < .001).

In the adjusted model that controlled for demographic characteristics, other medical comorbidities, and hospital location, the mortality risk somewhat decreased but still remained significantly higher (HR, 1.5; 95% CI, 1.1-1.9; P = .003).

Dr. Li noted a number of factors that might account for the higher mortality rate among psychiatric patients who had COVID-19 in comparison with COVD-19 patients who did not have a psychiatric disorder. These included “potential inflammatory and stress responses that the body experiences related to prior psychiatric conditions,” she said.

Having been previously diagnosed with a psychiatric disorder may also “reflect existing neurochemical differences, compared to those who do not have a prior psychiatric diagnosis, [and] these differences may make the population with the prior psychiatric diagnosis more vulnerable to respond to an acute stressor such as COVID-19,” she said.
 

Quality care

Harold Pincus, MD, professor and vice chair of the department of psychiatry at Columbia University, New York, said it “adds to the fairly well-known and well-established phenomenon that people with mental illnesses have a high risk of all sorts of morbidity and mortality for non–mental health conditions.”

The researchers “adjusted for various expected [mortality] risks that would be independent of the presence of COVID-19,” so “there was something else going on associated with mortality,” said Dr. Pincus, who is also codirector of the Irving Institute for Clinical and Translation Research. He was not involved with the study.

Beyond the possibility of “some basic immunologic process affected by the presence of a mental disorder,” it is possible that the vulnerability is “related to access to quality care for the comorbid general condition that is not being effectively treated,” he said.

“The take-home message is that people with mental disorders are at higher risk for death, and we need to make sure that, irrespective of COVID-19, they get adequate preventive and chronic-disease care, which would be the most effective way to intervene and protect the impact of a serious disease like COVID-19,” he noted. This would include being appropriately vaccinated and receiving preventive healthcare to reduce smoking and encourage weight loss.

No source of funding for the study was provided. Dr. Li reported receiving grants from a Health and Aging Policy Fellowship during the conduct of the study. Dr. Pincus reported no relevant financial relationships.

A psychiatric diagnosis for patients hospitalized with COVID-19 is linked to a significantly increased risk for death, new research shows.

Investigators found that patients who were hospitalized with COVID-19 and who had been diagnosed with a psychiatric disorder had a 50% increased risk for a COVID-related death in comparison with COVID-19 patients who had not received a psychiatric diagnosis.

“Pay attention and potentially address/treat a prior psychiatric diagnosis if a patient is hospitalized for COVID-19, as this risk factor can impact the patient’s outcome – death – while in the hospital,” lead investigator Luming Li, MD, assistant professor of psychiatry and associate medical director of quality improvement, Yale New Haven Psychiatric Hospital, New Haven, Conn., said in an interview.

The study was published Sept. 30 in JAMA Network Open.
 

Negative impact

“We were interested to learn more about the impact of psychiatric diagnoses on COVID-19 mortality, as prior large cohort studies included neurological and other medical conditions but did not assess for a priori psychiatric diagnoses,” said Dr. Li.

“We know from the literature that prior psychiatric diagnoses can have a negative impact on the outcomes of medical conditions, and therefore we tested our hypothesis on a cohort of patients who were hospitalized with COVID-19,” she added.

To investigate, the researchers analyzed data on 1,685 patients hospitalized with COVID-19 between Feb. 15 and April 25, 2020, and whose cases were followed to May 27, 2020. The patients (mean age, 65.2 years; 52.6% men) were drawn from the Yale New Haven Health System.

The median follow-up period was 8 days (interquartile range, 4-16 days) .

Of these patients, 28% had received a psychiatric diagnosis prior to hospitalization. The patients with psychiatric disorders were significantly older and were more likely to be women, White, non-Hispanic, and to have medical comorbidities (i.e., cancer, cerebrovascular disease, heart failure, diabetes, kidney disease, liver disease, MI, and/or HIV).

Psychiatric diagnoses were defined in accordance with ICD codes that included mental and behavioral health, Alzheimer’s disease, and self-injury.
 

Vulnerability to stress

In the unadjusted model, the risk for COVID-19–related hospital death was greater for those who had received any psychiatric diagnosis, compared with those had not (hazard ratio, 2.3; 95% CI, 1.8-2.9; P < .001).

In the adjusted model that controlled for demographic characteristics, other medical comorbidities, and hospital location, the mortality risk somewhat decreased but still remained significantly higher (HR, 1.5; 95% CI, 1.1-1.9; P = .003).

Dr. Li noted a number of factors that might account for the higher mortality rate among psychiatric patients who had COVID-19 in comparison with COVD-19 patients who did not have a psychiatric disorder. These included “potential inflammatory and stress responses that the body experiences related to prior psychiatric conditions,” she said.

Having been previously diagnosed with a psychiatric disorder may also “reflect existing neurochemical differences, compared to those who do not have a prior psychiatric diagnosis, [and] these differences may make the population with the prior psychiatric diagnosis more vulnerable to respond to an acute stressor such as COVID-19,” she said.
 

Quality care

Harold Pincus, MD, professor and vice chair of the department of psychiatry at Columbia University, New York, said it “adds to the fairly well-known and well-established phenomenon that people with mental illnesses have a high risk of all sorts of morbidity and mortality for non–mental health conditions.”

The researchers “adjusted for various expected [mortality] risks that would be independent of the presence of COVID-19,” so “there was something else going on associated with mortality,” said Dr. Pincus, who is also codirector of the Irving Institute for Clinical and Translation Research. He was not involved with the study.

Beyond the possibility of “some basic immunologic process affected by the presence of a mental disorder,” it is possible that the vulnerability is “related to access to quality care for the comorbid general condition that is not being effectively treated,” he said.

“The take-home message is that people with mental disorders are at higher risk for death, and we need to make sure that, irrespective of COVID-19, they get adequate preventive and chronic-disease care, which would be the most effective way to intervene and protect the impact of a serious disease like COVID-19,” he noted. This would include being appropriately vaccinated and receiving preventive healthcare to reduce smoking and encourage weight loss.

No source of funding for the study was provided. Dr. Li reported receiving grants from a Health and Aging Policy Fellowship during the conduct of the study. Dr. Pincus reported no relevant financial relationships.

Dr Patricia Coyle from Stony Brook University Medical Center in New York highlights new data on disease-modifying therapies (DMTs) from the 8th Joint ACTRIMS-ECTRIMS Meeting, MSVirtual2020.

Focusing on relapsing-remitting multiple sclerosis (RRMS), Dr Coyle discusses new research that further explores the efficacy and rebound effects of DMTs, 24 of which are approved in the United States for this patient population.

She reports on results from a database study comparing DMTs vs moderate-efficacy drugs and escalating treatment in the first-line setting, a cohort of pediatric patients receiving adult-approved teriflunomide, and an exploration of fingolimod rebound syndrome.

Patricia K. Coyle, MD, Professor, Interim Chair, Director, Multiple Sclerosis Comprehensive Care Center, Department of Neurology, Stony Brook University Medical Center, Stony Brook, New York

Dr Patricia Coyle from Stony Brook University Medical Center in New York highlights new data on disease-modifying therapies (DMTs) from the 8th Joint ACTRIMS-ECTRIMS Meeting, MSVirtual2020.

Focusing on relapsing-remitting multiple sclerosis (RRMS), Dr Coyle discusses new research that further explores the efficacy and rebound effects of DMTs, 24 of which are approved in the United States for this patient population.

She reports on results from a database study comparing DMTs vs moderate-efficacy drugs and escalating treatment in the first-line setting, a cohort of pediatric patients receiving adult-approved teriflunomide, and an exploration of fingolimod rebound syndrome.

Patricia K. Coyle, MD, Professor, Interim Chair, Director, Multiple Sclerosis Comprehensive Care Center, Department of Neurology, Stony Brook University Medical Center, Stony Brook, New York

Dr Patricia Coyle from Stony Brook University Medical Center in New York highlights new data on disease-modifying therapies (DMTs) from the 8th Joint ACTRIMS-ECTRIMS Meeting, MSVirtual2020.

Focusing on relapsing-remitting multiple sclerosis (RRMS), Dr Coyle discusses new research that further explores the efficacy and rebound effects of DMTs, 24 of which are approved in the United States for this patient population.

She reports on results from a database study comparing DMTs vs moderate-efficacy drugs and escalating treatment in the first-line setting, a cohort of pediatric patients receiving adult-approved teriflunomide, and an exploration of fingolimod rebound syndrome.

Patricia K. Coyle, MD, Professor, Interim Chair, Director, Multiple Sclerosis Comprehensive Care Center, Department of Neurology, Stony Brook University Medical Center, Stony Brook, New York

Pancreatic fluid collections (PFCs) are common after acute pancreatitis but almost always resolve spontaneously. Persistent collections that cause symptoms, become infected, and/or compress vital structures require treatment. Open surgery had traditionally been considered the standard method for this indication; however, major paradigm shifts over the last 2 decades have resulted in the adoption and diffusion of a minimally invasive “step-up” approach.¹ Given its inherently less invasive nature, endoscopic transmural drainage (ETMD) has become a mainstay of this step-up philosophy – it is now the dominant strategy for pseudocyst drainage and, on the basis of emerging randomized trial data, compares very favorably with surgery for the treatment of walled-off necrosis (WON).

According to the step-up approach, the initial treatment of symptomatic and/or infected collections that are within 4 weeks of an attack of pancreatitis involves conservative management because the wall of the collection is typically immature; the systemic inflammation may be significantly exacerbated by definitive drainage, particularly surgery. In this early phase, failure of conservative management is addressed by percutaneous catheter placement, stepping up to a minimally invasive operation if the response to percutaneous drainage and antibiotics is insufficient.

Collections that are at least 4 weeks from the onset of acute pancreatitis are considered mature and termed pseudocysts or WONs depending on whether they contain pure fluid or necrotic tissue. In this phase, endoscopic treatment plays a primary management role because these collections are generally adherent to the stomach or duodenal wall and their capsule is organized enough to withstand endoscopic intervention. If treatment can be held off until this phase, then percutaneous and surgical drainage can often be avoided.

In practice, the 4-week rule holds true for most, but not all, PFCs. ETMD can be performed in some particularly mature collections prior to 4 weeks if the indication is strong and the collection appears to have a mature wall. However, the potential for cyst wall perforation is higher and should be considered in the risk-benefit discussion. Conversely, some collections beyond 4 weeks lack an adequately organized wall and require additional time for maturation.

While endoscopic drainage of pseudocysts has essentially supplanted surgery, the management of WON is more complex and remains multidisciplinary. Two recent randomized trials demonstrated no difference in major complications and/or death between a surgical and endoscopic step-up strategy for WON.^2,3 Rates of pancreatic fistulae, hospital stay, and overall treatment costs, however, favored endoscopy. Nevertheless, defining the ideal strategy for many of these patients with complexity requires multidisciplinary discussion. Surgery continues to play a primary role in several scenarios, including collections that are not close to the upper GI tract, those that are particularly complex and extend caudally, and situations in which the endoscopic progress is too slow.

The three most important questions when deciding to embark on ETMD are: (1) whether drainage is indicated (that is, is the patient symptomatic or is there evidence that the PFC is infected?), (2) whether the wall of the collection is adequately mature and apposed to the GI tract wall; and (3) whether the collection contains necrosis? This last question has critical implications in the technical approach to drainage. While CT scan with IV contrast is accurate for assessing wall maturity, it is inadequate to evaluate the presence or quantity of necrosum. Transabdominal ultrasound, endoscopic ultrasound, and MRI (on a T2 sequence) are all superior for this purpose. MRI has the additional benefit of assessing the pancreatic duct integrity, which may influence subsequent management.

References

1. van Santvoort HC et al. N Engl J Med. 2010;362(16):1491-502.

2. van Brunschot S et al. Lancet. 2018;391(10115):51-8.

3. Bang JY et al. Gastroenterology. 2019;156(4):1027-40.

4. Bang JY et al. Gut. 2019;68(7):1200-9.

5. Elmunzer BJ. Clin Gastroenterol Hepatol. 2018;16(12):1851-63.

Dr. Moran is assistant professor of medicine, division of gastroenterology and hepatology, Medical University of South Carolina, Charleston; Dr. Elmunzer is the Peter Cotton Professor of Medicine and Endoscopic Innovation, division of gastroenterology and hepatology, Medical University of South Carolina. The authors have no conflicts of interest pertaining to this review.

Pancreatic fluid collections (PFCs) are common after acute pancreatitis but almost always resolve spontaneously. Persistent collections that cause symptoms, become infected, and/or compress vital structures require treatment. Open surgery had traditionally been considered the standard method for this indication; however, major paradigm shifts over the last 2 decades have resulted in the adoption and diffusion of a minimally invasive “step-up” approach.¹ Given its inherently less invasive nature, endoscopic transmural drainage (ETMD) has become a mainstay of this step-up philosophy – it is now the dominant strategy for pseudocyst drainage and, on the basis of emerging randomized trial data, compares very favorably with surgery for the treatment of walled-off necrosis (WON).

According to the step-up approach, the initial treatment of symptomatic and/or infected collections that are within 4 weeks of an attack of pancreatitis involves conservative management because the wall of the collection is typically immature; the systemic inflammation may be significantly exacerbated by definitive drainage, particularly surgery. In this early phase, failure of conservative management is addressed by percutaneous catheter placement, stepping up to a minimally invasive operation if the response to percutaneous drainage and antibiotics is insufficient.

Collections that are at least 4 weeks from the onset of acute pancreatitis are considered mature and termed pseudocysts or WONs depending on whether they contain pure fluid or necrotic tissue. In this phase, endoscopic treatment plays a primary management role because these collections are generally adherent to the stomach or duodenal wall and their capsule is organized enough to withstand endoscopic intervention. If treatment can be held off until this phase, then percutaneous and surgical drainage can often be avoided.

In practice, the 4-week rule holds true for most, but not all, PFCs. ETMD can be performed in some particularly mature collections prior to 4 weeks if the indication is strong and the collection appears to have a mature wall. However, the potential for cyst wall perforation is higher and should be considered in the risk-benefit discussion. Conversely, some collections beyond 4 weeks lack an adequately organized wall and require additional time for maturation.

While endoscopic drainage of pseudocysts has essentially supplanted surgery, the management of WON is more complex and remains multidisciplinary. Two recent randomized trials demonstrated no difference in major complications and/or death between a surgical and endoscopic step-up strategy for WON.^2,3 Rates of pancreatic fistulae, hospital stay, and overall treatment costs, however, favored endoscopy. Nevertheless, defining the ideal strategy for many of these patients with complexity requires multidisciplinary discussion. Surgery continues to play a primary role in several scenarios, including collections that are not close to the upper GI tract, those that are particularly complex and extend caudally, and situations in which the endoscopic progress is too slow.

The three most important questions when deciding to embark on ETMD are: (1) whether drainage is indicated (that is, is the patient symptomatic or is there evidence that the PFC is infected?), (2) whether the wall of the collection is adequately mature and apposed to the GI tract wall; and (3) whether the collection contains necrosis? This last question has critical implications in the technical approach to drainage. While CT scan with IV contrast is accurate for assessing wall maturity, it is inadequate to evaluate the presence or quantity of necrosum. Transabdominal ultrasound, endoscopic ultrasound, and MRI (on a T2 sequence) are all superior for this purpose. MRI has the additional benefit of assessing the pancreatic duct integrity, which may influence subsequent management.

References

1. van Santvoort HC et al. N Engl J Med. 2010;362(16):1491-502.

2. van Brunschot S et al. Lancet. 2018;391(10115):51-8.

3. Bang JY et al. Gastroenterology. 2019;156(4):1027-40.

4. Bang JY et al. Gut. 2019;68(7):1200-9.

5. Elmunzer BJ. Clin Gastroenterol Hepatol. 2018;16(12):1851-63.

Dr. Moran is assistant professor of medicine, division of gastroenterology and hepatology, Medical University of South Carolina, Charleston; Dr. Elmunzer is the Peter Cotton Professor of Medicine and Endoscopic Innovation, division of gastroenterology and hepatology, Medical University of South Carolina. The authors have no conflicts of interest pertaining to this review.

Pancreatic fluid collections (PFCs) are common after acute pancreatitis but almost always resolve spontaneously. Persistent collections that cause symptoms, become infected, and/or compress vital structures require treatment. Open surgery had traditionally been considered the standard method for this indication; however, major paradigm shifts over the last 2 decades have resulted in the adoption and diffusion of a minimally invasive “step-up” approach.¹ Given its inherently less invasive nature, endoscopic transmural drainage (ETMD) has become a mainstay of this step-up philosophy – it is now the dominant strategy for pseudocyst drainage and, on the basis of emerging randomized trial data, compares very favorably with surgery for the treatment of walled-off necrosis (WON).

According to the step-up approach, the initial treatment of symptomatic and/or infected collections that are within 4 weeks of an attack of pancreatitis involves conservative management because the wall of the collection is typically immature; the systemic inflammation may be significantly exacerbated by definitive drainage, particularly surgery. In this early phase, failure of conservative management is addressed by percutaneous catheter placement, stepping up to a minimally invasive operation if the response to percutaneous drainage and antibiotics is insufficient.

Collections that are at least 4 weeks from the onset of acute pancreatitis are considered mature and termed pseudocysts or WONs depending on whether they contain pure fluid or necrotic tissue. In this phase, endoscopic treatment plays a primary management role because these collections are generally adherent to the stomach or duodenal wall and their capsule is organized enough to withstand endoscopic intervention. If treatment can be held off until this phase, then percutaneous and surgical drainage can often be avoided.

In practice, the 4-week rule holds true for most, but not all, PFCs. ETMD can be performed in some particularly mature collections prior to 4 weeks if the indication is strong and the collection appears to have a mature wall. However, the potential for cyst wall perforation is higher and should be considered in the risk-benefit discussion. Conversely, some collections beyond 4 weeks lack an adequately organized wall and require additional time for maturation.

While endoscopic drainage of pseudocysts has essentially supplanted surgery, the management of WON is more complex and remains multidisciplinary. Two recent randomized trials demonstrated no difference in major complications and/or death between a surgical and endoscopic step-up strategy for WON.^2,3 Rates of pancreatic fistulae, hospital stay, and overall treatment costs, however, favored endoscopy. Nevertheless, defining the ideal strategy for many of these patients with complexity requires multidisciplinary discussion. Surgery continues to play a primary role in several scenarios, including collections that are not close to the upper GI tract, those that are particularly complex and extend caudally, and situations in which the endoscopic progress is too slow.

The three most important questions when deciding to embark on ETMD are: (1) whether drainage is indicated (that is, is the patient symptomatic or is there evidence that the PFC is infected?), (2) whether the wall of the collection is adequately mature and apposed to the GI tract wall; and (3) whether the collection contains necrosis? This last question has critical implications in the technical approach to drainage. While CT scan with IV contrast is accurate for assessing wall maturity, it is inadequate to evaluate the presence or quantity of necrosum. Transabdominal ultrasound, endoscopic ultrasound, and MRI (on a T2 sequence) are all superior for this purpose. MRI has the additional benefit of assessing the pancreatic duct integrity, which may influence subsequent management.

References

1. van Santvoort HC et al. N Engl J Med. 2010;362(16):1491-502.

2. van Brunschot S et al. Lancet. 2018;391(10115):51-8.

3. Bang JY et al. Gastroenterology. 2019;156(4):1027-40.

4. Bang JY et al. Gut. 2019;68(7):1200-9.

5. Elmunzer BJ. Clin Gastroenterol Hepatol. 2018;16(12):1851-63.

Dr. Moran is assistant professor of medicine, division of gastroenterology and hepatology, Medical University of South Carolina, Charleston; Dr. Elmunzer is the Peter Cotton Professor of Medicine and Endoscopic Innovation, division of gastroenterology and hepatology, Medical University of South Carolina. The authors have no conflicts of interest pertaining to this review.

For patients with central centrifugal cicatricial alopecia (CCCA), several therapies showing benefit in case studies might reasonably be considered for those who have failed standard interventions, according to a review of current strategies for this challenging disease, delivered at the virtual Skin of Color Update 2020.

Courtesy Johns Hopkins Medicine

Two case reports of favorable results with topical metformin were published earlier this year. A subsequent case in which metformin provided a major improvement in quality of life has provided further encouragement, according to Crystal Aguh, MD, director of the ethnic skin program at Johns Hopkins University, Baltimore.

In the subsequent case, there was complete scalp coverage, allowing the patient to no longer use a wig, which is “tough to achieve in patients with advanced disease,” Dr. Aguh said.

In the two published cases, 10% metformin compounded in Lipoderm (PCCA) produced notable hair growth within 6 months. Dr. Aguh said that the case studies were prompted by experimental evidence associating metformin with an antifibrotic effect.

This finding is potentially important. Most current treatments for CCCA are based on anti-inflammatory activity, according to Dr. Aguh, but fibrosis is strongly implicated in the pathogenesis of CCCA. Of several lines of evidence, one is the association between CCCA and other fibrosing conditions.

For example, women with CCCA “are several times more likely to have uterine fibroids than women without CCCA,” said Dr. Aguh, citing a study that she published in 2018. She suggested that there is an urgent need for new treatment options because of the “often-disappointing” responses to current standard therapies.

In the CCCA cases treated so far, topical metformin has been well tolerated, which is attributed to the low level of systemic absorption. No nausea or other gastrointestinal side effects common to oral metformin have been so far observed in Dr. Aguh’s cases.

“Some patients experience scalp dryness or irritation,” she said, but added that a light coating of emollient typically relieves this complaint.

Despite the promising results, topical metformin “is not a silver bullet,” Dr. Aguh cautioned. She estimated that only 10%-15% of patients respond, but this treatment can be considered “as an adjunctive option to avoid another round of intralesional steroids.”

Platelet-rich plasma (PRP) is another option that has demonstrated promise in a published case report for which Dr. Aguh served as a coauthor. In this series of two patients, only one had CCCA. The other had lichen planopilaris, but both patients experienced hair regrowth after failing standard therapies.

When treating alopecia with PRP, Dr. Aguh typically offers three or four sessions spaced 4 weeks apart. She does not start other treatments at the same time, but she does not discontinue topical treatments that patients are already taking, including topical minoxidil.

Again, like topical metformin, PRP is reasonably considered in patients who have failed standard therapies, according to Dr. Aguh. She cautioned that responses are not permanent. Patients who respond typically require retreatment a year or more later, but good responses have been seen after retreatment.

Appropriate hair care can help. Dr. Aguh recounted a case in which a patient with presumed CCCA was referred after failing intralesional triamcinolone injections. Ultimately, the patient was diagnosed with acquired trichorrhexis nodosa, but the large clinical improvements gained from better hair care practices, including avoidance of chemical relaxants and thermal styling, are relevant to CCCA, as well as other conditions resulting in hair loss.

In a book written by Dr. Aguh, titled “90 Days to Beautiful Hair,” strategies for better hair care practices include advice to reduce tension on hair follicles.

The role of increased traction is an issue in CCCA, agreed Amy McMichael, MD, chair of the department of dermatology, Wake Forest University, Winston-Salem, N.C. Although she provided data at the meeting suggesting that CCCA is a fibrosing disease linked to genetic susceptibility, she said there is also a “strong association” between the severity of CCCA and extensions, hair weaving, and other tension-associated hairstyles.

While there is an urgent need to develop therapies that address the underlying pathophysiology of CCCA, she concurred that patients with this or other conditions associated with hair loss, such as seborrheic dermatitis or frontal fibrosing alopecia, should not ignore appropriate hair care.

Dr. Aguh has financial relationships with LEO Pharma and UCB Pharma. Dr. McMichael’s disclosures included serving as an investigator and/or consultant for companies that included Allergan, Procter & Gamble, Nutrafol, Johnson & Johnson, and Aclaris.

For patients with central centrifugal cicatricial alopecia (CCCA), several therapies showing benefit in case studies might reasonably be considered for those who have failed standard interventions, according to a review of current strategies for this challenging disease, delivered at the virtual Skin of Color Update 2020.

Courtesy Johns Hopkins Medicine

Two case reports of favorable results with topical metformin were published earlier this year. A subsequent case in which metformin provided a major improvement in quality of life has provided further encouragement, according to Crystal Aguh, MD, director of the ethnic skin program at Johns Hopkins University, Baltimore.

In the subsequent case, there was complete scalp coverage, allowing the patient to no longer use a wig, which is “tough to achieve in patients with advanced disease,” Dr. Aguh said.

In the two published cases, 10% metformin compounded in Lipoderm (PCCA) produced notable hair growth within 6 months. Dr. Aguh said that the case studies were prompted by experimental evidence associating metformin with an antifibrotic effect.

This finding is potentially important. Most current treatments for CCCA are based on anti-inflammatory activity, according to Dr. Aguh, but fibrosis is strongly implicated in the pathogenesis of CCCA. Of several lines of evidence, one is the association between CCCA and other fibrosing conditions.

For example, women with CCCA “are several times more likely to have uterine fibroids than women without CCCA,” said Dr. Aguh, citing a study that she published in 2018. She suggested that there is an urgent need for new treatment options because of the “often-disappointing” responses to current standard therapies.

In the CCCA cases treated so far, topical metformin has been well tolerated, which is attributed to the low level of systemic absorption. No nausea or other gastrointestinal side effects common to oral metformin have been so far observed in Dr. Aguh’s cases.

“Some patients experience scalp dryness or irritation,” she said, but added that a light coating of emollient typically relieves this complaint.

Despite the promising results, topical metformin “is not a silver bullet,” Dr. Aguh cautioned. She estimated that only 10%-15% of patients respond, but this treatment can be considered “as an adjunctive option to avoid another round of intralesional steroids.”

Platelet-rich plasma (PRP) is another option that has demonstrated promise in a published case report for which Dr. Aguh served as a coauthor. In this series of two patients, only one had CCCA. The other had lichen planopilaris, but both patients experienced hair regrowth after failing standard therapies.

When treating alopecia with PRP, Dr. Aguh typically offers three or four sessions spaced 4 weeks apart. She does not start other treatments at the same time, but she does not discontinue topical treatments that patients are already taking, including topical minoxidil.

Again, like topical metformin, PRP is reasonably considered in patients who have failed standard therapies, according to Dr. Aguh. She cautioned that responses are not permanent. Patients who respond typically require retreatment a year or more later, but good responses have been seen after retreatment.

Appropriate hair care can help. Dr. Aguh recounted a case in which a patient with presumed CCCA was referred after failing intralesional triamcinolone injections. Ultimately, the patient was diagnosed with acquired trichorrhexis nodosa, but the large clinical improvements gained from better hair care practices, including avoidance of chemical relaxants and thermal styling, are relevant to CCCA, as well as other conditions resulting in hair loss.

In a book written by Dr. Aguh, titled “90 Days to Beautiful Hair,” strategies for better hair care practices include advice to reduce tension on hair follicles.

The role of increased traction is an issue in CCCA, agreed Amy McMichael, MD, chair of the department of dermatology, Wake Forest University, Winston-Salem, N.C. Although she provided data at the meeting suggesting that CCCA is a fibrosing disease linked to genetic susceptibility, she said there is also a “strong association” between the severity of CCCA and extensions, hair weaving, and other tension-associated hairstyles.

While there is an urgent need to develop therapies that address the underlying pathophysiology of CCCA, she concurred that patients with this or other conditions associated with hair loss, such as seborrheic dermatitis or frontal fibrosing alopecia, should not ignore appropriate hair care.

Dr. Aguh has financial relationships with LEO Pharma and UCB Pharma. Dr. McMichael’s disclosures included serving as an investigator and/or consultant for companies that included Allergan, Procter & Gamble, Nutrafol, Johnson & Johnson, and Aclaris.

For patients with central centrifugal cicatricial alopecia (CCCA), several therapies showing benefit in case studies might reasonably be considered for those who have failed standard interventions, according to a review of current strategies for this challenging disease, delivered at the virtual Skin of Color Update 2020.

Courtesy Johns Hopkins Medicine

Two case reports of favorable results with topical metformin were published earlier this year. A subsequent case in which metformin provided a major improvement in quality of life has provided further encouragement, according to Crystal Aguh, MD, director of the ethnic skin program at Johns Hopkins University, Baltimore.

In the subsequent case, there was complete scalp coverage, allowing the patient to no longer use a wig, which is “tough to achieve in patients with advanced disease,” Dr. Aguh said.

In the two published cases, 10% metformin compounded in Lipoderm (PCCA) produced notable hair growth within 6 months. Dr. Aguh said that the case studies were prompted by experimental evidence associating metformin with an antifibrotic effect.

This finding is potentially important. Most current treatments for CCCA are based on anti-inflammatory activity, according to Dr. Aguh, but fibrosis is strongly implicated in the pathogenesis of CCCA. Of several lines of evidence, one is the association between CCCA and other fibrosing conditions.

For example, women with CCCA “are several times more likely to have uterine fibroids than women without CCCA,” said Dr. Aguh, citing a study that she published in 2018. She suggested that there is an urgent need for new treatment options because of the “often-disappointing” responses to current standard therapies.

In the CCCA cases treated so far, topical metformin has been well tolerated, which is attributed to the low level of systemic absorption. No nausea or other gastrointestinal side effects common to oral metformin have been so far observed in Dr. Aguh’s cases.

“Some patients experience scalp dryness or irritation,” she said, but added that a light coating of emollient typically relieves this complaint.

Despite the promising results, topical metformin “is not a silver bullet,” Dr. Aguh cautioned. She estimated that only 10%-15% of patients respond, but this treatment can be considered “as an adjunctive option to avoid another round of intralesional steroids.”

Platelet-rich plasma (PRP) is another option that has demonstrated promise in a published case report for which Dr. Aguh served as a coauthor. In this series of two patients, only one had CCCA. The other had lichen planopilaris, but both patients experienced hair regrowth after failing standard therapies.

When treating alopecia with PRP, Dr. Aguh typically offers three or four sessions spaced 4 weeks apart. She does not start other treatments at the same time, but she does not discontinue topical treatments that patients are already taking, including topical minoxidil.

Again, like topical metformin, PRP is reasonably considered in patients who have failed standard therapies, according to Dr. Aguh. She cautioned that responses are not permanent. Patients who respond typically require retreatment a year or more later, but good responses have been seen after retreatment.

Appropriate hair care can help. Dr. Aguh recounted a case in which a patient with presumed CCCA was referred after failing intralesional triamcinolone injections. Ultimately, the patient was diagnosed with acquired trichorrhexis nodosa, but the large clinical improvements gained from better hair care practices, including avoidance of chemical relaxants and thermal styling, are relevant to CCCA, as well as other conditions resulting in hair loss.

In a book written by Dr. Aguh, titled “90 Days to Beautiful Hair,” strategies for better hair care practices include advice to reduce tension on hair follicles.

The role of increased traction is an issue in CCCA, agreed Amy McMichael, MD, chair of the department of dermatology, Wake Forest University, Winston-Salem, N.C. Although she provided data at the meeting suggesting that CCCA is a fibrosing disease linked to genetic susceptibility, she said there is also a “strong association” between the severity of CCCA and extensions, hair weaving, and other tension-associated hairstyles.

While there is an urgent need to develop therapies that address the underlying pathophysiology of CCCA, she concurred that patients with this or other conditions associated with hair loss, such as seborrheic dermatitis or frontal fibrosing alopecia, should not ignore appropriate hair care.

Dr. Aguh has financial relationships with LEO Pharma and UCB Pharma. Dr. McMichael’s disclosures included serving as an investigator and/or consultant for companies that included Allergan, Procter & Gamble, Nutrafol, Johnson & Johnson, and Aclaris.

A recent review looked at all articles describing skin manifestations associated with COVID-19 – 46 articles with a total of 130 clinical images – and found none that documented dermatologic conditions in people with dark skin. This was despite the disproportionate incidence of the disease in Black, Latino, and Native American/American Indian populations of color.

What’s going on? Temitayo Ogunleye, MD, an assistant professor of dermatology at the University of Pennsylvania, Philadelphia, spoke with lead investigator Jenna Lester, MD, a dermatologist and director of the Skin of Color Clinic at University of California, San Francisco, about the implications of her research.

Dr. Ogunleye: What prompted you to do this study in the first place?

Dr. Lester: It was actually driven by frustration. While we’re recognizing these COVID-related dermatologic manifestations, we’re still trying to figure out their clinical significance. We’ve learned what changes could be an early sign of infection and what might occur in people who are otherwise asymptomatic and should be tested. But in the process, we’re leaving out the group of people – dark-skinned populations – who are most heavily impacted by COVID. This is an injustice to the people who could benefit the most if found to have an early, visible sign of the disease on their skin. For example, pernio-like lesions and erythema, both of which have been seen in COVID patients, are harder to identify in darker skin.

As dermatologists, we know that the skin is the biggest organ and one that has the advantage of being visible. We partner with patients because they can see what we can see. We can explain what skin changes mean, and having examples to show them is really powerful. Because doctors typically respond best to numbers, I recognized that we needed data to prove that this lack of representation of persons of color in our COVID documentation was in fact true.

Can you tell us the key findings from your research?

We included any article that described the cutaneous manifestations of COVID – and also included a photograph – and was published over a period of 5 months. Then we categorized each image using the Fitzpatrick Skin Type Scale. We found that the majority of the photos were of people with light skin; there were no images at all of patients with dark skin, Fitzpatrick type V or VI. A handful, about 6%, depicted skin changes in patients with Fitzpatrick type IV skin.

Were you surprised by the findings?

No. I was not surprised at all, for a couple of reasons. First, many of the referrals that I had been getting to evaluate possible COVID manifestations were from primary care doctors. And as we both know, erythema, hyperpigmentation, and discoloration can be difficult for even a trained dermatologist to pick up on. So if these patients with skin changes potentially suggestive of COVID are presenting to their primary care doctor who could not determine what they were, perhaps because they had never seen them in someone with darker skin, it means those same clinicians are not likely to document these rashes. I suspect that a lot of these photos were sourced from primary care.

The other reason for my lack of surprise is that I have looked at this issue before. In a study I did in 2019 looking at images in dermatology textbooks, my coauthors and I found that there was a pretty dramatic underrepresentation of skin of color overall. Another analysis of images in core dermatology textbooks, published earlier this year by one of your colleagues at the University of Pennsylvania, Jules Lipoff, MD, showed that the percentage of images of dark skin ranged from as low as 4% to a high of about 18%.

So I wonder whether that makes us less likely to look for things in patients with darker skin, except for those conditions that we’re taught are more common in people with darker skin, like keloids, vitiligo, or certain types of hair loss. I wonder whether we just don’t think of other conditions because all the photos we ever see of psoriasis or rosacea, for example, are of people with lighter skin.

You bring up a good point about the cyclical nature of this process. If you don’t see skin conditions in darker skin, then you don’t know what to look for and so you never look for it.

Exactly. What if a Black patient says, for example: “This looks different on my skin; do you think this could be related to COVID?” And their doctor looks at their skin and says no. Not because it isn’t, but because they haven’t seen that before. Then they don’t take a picture of it and we’ll never know what that might have been.

The disturbing thing I have found is that there is an overrepresentation of dark skin in images of sexually transmitted infections. So based on what you are taught, you begin to create these powerful cognitive biases in your brain as a clinician and you start to put people in categories: “This person is more likely to get this because I’ve seen a lot of photos of it.”

Take the example of a 40ish Black woman with a cough who is presumed to have sarcoidosis, because we’ve all been taught that. But what we have not been taught, at least not as definitively, is that the highest prevalence of sarcoidosis is in Nordic countries, where there are not many Black people.

So these loops teach you things that don’t necessarily represent reality. We are taught to recognize patterns, but the patterns that we’ve created are not necessarily valid and carry the biases of the people who decided they were important for us to learn.
 

So the underrepresentation of persons of color in images depicting skin changes in COVID-19 is, in your perspective, a continuation of this pattern of bias?

I definitely think it is. It’s important to understand the history of photography and the development of color film in order to contextualize that question. Kodak Gold was one of the first color films made. To assist photographers, the company developed a Shirley card, which could be used for color balancing in developing this film. That card, which was distributed to film development labs across the country, depicted a fair-skinned White woman as the standard for how people should appear in the photograph. Film technology was built around this idea.

As a result, people with darker skin were never portrayed accurately and did not have a lot of detail to their features or their skin. A number of famous photographers boycotted by not using the film.

But it wasn’t until chocolate manufacturers and the furniture industries decided that Kodak Gold film was not showing their brown products in enough detail that Kodak was forced to change.

It took these big industries saying “we’re not going to use your film anymore” to spur the development of multicultural Shirley cards which included images of Asian, White, and Black women (a Latina was added later). That didn’t happen until 1995. By then, digital photography had already started to take off. Unfortunately, that advance built off of the original color film and still harbored some of the same issues.

So in addition to concerns about clinicians not recognizing a skin change in a darker-skinned person, if they do recognize it and do decide to photograph it, it just might not come out right. So then it’s possible that clinicians just decide to stop taking photos.

This is another example of structural racism – things that are just baked into the system about which people are unaware. I fear we’ll continue to perpetuate these unconscious biases with the development of augmented intelligence or various algorithms.

I think that this history – which I was unaware of – highlights what happens when White skin becomes the standard. It certainly explains the issue we’ve both seen of clinicians not recognizing erythema on dark skin.

That’s a big one. And I think it’s a big one because it’s a shared presenting sign of a lot of different rashes. It can also be a sign of a dermatologic emergency that requires rapid recognition and treatment. Erythema can be very subtle, especially in skin of color. It is one of the things that we use to grade severity of psoriasis, and as a result of it not being appreciated in people with darker skin, those patients have not been included in a lot of the clinical trials.

There has even been discussion of whether erythema is something we should deem to be an important finding in people with darker skin.

Maybe one of the problems is terminology. Erythema connotes pink or red coloration, and that does not really show up on dark skin as overtly.

Exactly. Emollient use is also different in people of color. So the “classic” scales of psoriasis often aren’t present in someone who uses a lot of lotion.

In addition to the different clinical appearance of many common skin conditions, cultural practices might be different in different groups, which may also alter your differential diagnoses and treatment recommendations – for instance, moisturizer use, shampooing frequency, or use of different hair styling products.

I totally agree. Hair is another big one. Identifying broken hairs, short hairs, texture changes, and variability in the size of the hair shaft is different in coiled, Black hair and is not really applicable to people with more textured hair patterns. People of different ethnicities and cultures do different things. Standards that we traditionally use, such as the hair-pull test, don’t work quite as well in different groups.

I think that speaks to the changes that we also need to make in educating both dermatologists and nondermatologists in diagnostic criteria and clinical findings.

Dermatology is the second least diverse specialty. And that means our experts – faculty, lecturers, mentors – are not likely to be people of color. You don’t know what you don’t know. You only have your own experiences. If you don’t have people who can explain why something may be different for a different group of people, you don’t have an opportunity to broaden your understanding. You and I noticed because we know what it’s like to have this type of hair. But it’s not something that other people who don’t share the same hair type would have the same perspective on.

It is even more reason to make sure that our dermatology workforce mirrors our population. About 3% of the dermatologists in the United States are Black; the numbers are equally bad for Latino and indigenous dermatologists. If you don’t have enough people in your immediate environment who can help broaden your perspective, that becomes a problem that can harm patients.

If we don’t have a diverse group of people in the field who are contributing to the literature, changing some of the ways that we think about practice, then everyone is just going to keep doing the wrong thing.

We need to build our evidence and pay more attention to the racial breakdown of patients included in studies. We are recognizing that we have blind spots but we don’t have people or data that can change that. If what we are publishing overrepresents a certain group, how will we ever learn to do things differently?

I recognize the fact that this is not a new idea. Others have worked on these issues for a long time. Your colleague, Susan Taylor, MD, a professor at University of Pennsylvania and a founder of the Skin of Color Society, used her energy and frustration about this issue and published a whole textbook on it: “Dermatology for Skin of Color.” When I tried to publish my first paper on this issue, I got a lot of pushback, but I’m happy that now it’s something that everyone is talking about. So just in the span of a couple of years, the acceptance of this idea has changed dramatically.

I hope that this is the start of sustainable, systemic changes that can have a real impact.

Let me ask a technical question. Is the excuse of not knowing how to photograph darker skin just that – an excuse? Or is that concern truly valid?

That’s a great question. There are certain techniques that one can employ. And yes, it can be more challenging if you are not used to taking photos of people with darker skin, but it certainly can be learned.

I think that an intelligent group of people who have faced things before that felt insurmountable could continue to push to figure out how to do it. But it is something that does require skills, and part of it is because there’s this bias built into the camera, so you have to make up for that.

I think every single dermatologist has that ability, and you just have to know that it’s worthwhile to do because your patient is that valuable.

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

A recent review looked at all articles describing skin manifestations associated with COVID-19 – 46 articles with a total of 130 clinical images – and found none that documented dermatologic conditions in people with dark skin. This was despite the disproportionate incidence of the disease in Black, Latino, and Native American/American Indian populations of color.

What’s going on? Temitayo Ogunleye, MD, an assistant professor of dermatology at the University of Pennsylvania, Philadelphia, spoke with lead investigator Jenna Lester, MD, a dermatologist and director of the Skin of Color Clinic at University of California, San Francisco, about the implications of her research.

Dr. Ogunleye: What prompted you to do this study in the first place?

Dr. Lester: It was actually driven by frustration. While we’re recognizing these COVID-related dermatologic manifestations, we’re still trying to figure out their clinical significance. We’ve learned what changes could be an early sign of infection and what might occur in people who are otherwise asymptomatic and should be tested. But in the process, we’re leaving out the group of people – dark-skinned populations – who are most heavily impacted by COVID. This is an injustice to the people who could benefit the most if found to have an early, visible sign of the disease on their skin. For example, pernio-like lesions and erythema, both of which have been seen in COVID patients, are harder to identify in darker skin.

As dermatologists, we know that the skin is the biggest organ and one that has the advantage of being visible. We partner with patients because they can see what we can see. We can explain what skin changes mean, and having examples to show them is really powerful. Because doctors typically respond best to numbers, I recognized that we needed data to prove that this lack of representation of persons of color in our COVID documentation was in fact true.

Can you tell us the key findings from your research?

We included any article that described the cutaneous manifestations of COVID – and also included a photograph – and was published over a period of 5 months. Then we categorized each image using the Fitzpatrick Skin Type Scale. We found that the majority of the photos were of people with light skin; there were no images at all of patients with dark skin, Fitzpatrick type V or VI. A handful, about 6%, depicted skin changes in patients with Fitzpatrick type IV skin.

Were you surprised by the findings?

No. I was not surprised at all, for a couple of reasons. First, many of the referrals that I had been getting to evaluate possible COVID manifestations were from primary care doctors. And as we both know, erythema, hyperpigmentation, and discoloration can be difficult for even a trained dermatologist to pick up on. So if these patients with skin changes potentially suggestive of COVID are presenting to their primary care doctor who could not determine what they were, perhaps because they had never seen them in someone with darker skin, it means those same clinicians are not likely to document these rashes. I suspect that a lot of these photos were sourced from primary care.

The other reason for my lack of surprise is that I have looked at this issue before. In a study I did in 2019 looking at images in dermatology textbooks, my coauthors and I found that there was a pretty dramatic underrepresentation of skin of color overall. Another analysis of images in core dermatology textbooks, published earlier this year by one of your colleagues at the University of Pennsylvania, Jules Lipoff, MD, showed that the percentage of images of dark skin ranged from as low as 4% to a high of about 18%.

So I wonder whether that makes us less likely to look for things in patients with darker skin, except for those conditions that we’re taught are more common in people with darker skin, like keloids, vitiligo, or certain types of hair loss. I wonder whether we just don’t think of other conditions because all the photos we ever see of psoriasis or rosacea, for example, are of people with lighter skin.

You bring up a good point about the cyclical nature of this process. If you don’t see skin conditions in darker skin, then you don’t know what to look for and so you never look for it.

Exactly. What if a Black patient says, for example: “This looks different on my skin; do you think this could be related to COVID?” And their doctor looks at their skin and says no. Not because it isn’t, but because they haven’t seen that before. Then they don’t take a picture of it and we’ll never know what that might have been.

The disturbing thing I have found is that there is an overrepresentation of dark skin in images of sexually transmitted infections. So based on what you are taught, you begin to create these powerful cognitive biases in your brain as a clinician and you start to put people in categories: “This person is more likely to get this because I’ve seen a lot of photos of it.”

Take the example of a 40ish Black woman with a cough who is presumed to have sarcoidosis, because we’ve all been taught that. But what we have not been taught, at least not as definitively, is that the highest prevalence of sarcoidosis is in Nordic countries, where there are not many Black people.

So these loops teach you things that don’t necessarily represent reality. We are taught to recognize patterns, but the patterns that we’ve created are not necessarily valid and carry the biases of the people who decided they were important for us to learn.
 

So the underrepresentation of persons of color in images depicting skin changes in COVID-19 is, in your perspective, a continuation of this pattern of bias?

I definitely think it is. It’s important to understand the history of photography and the development of color film in order to contextualize that question. Kodak Gold was one of the first color films made. To assist photographers, the company developed a Shirley card, which could be used for color balancing in developing this film. That card, which was distributed to film development labs across the country, depicted a fair-skinned White woman as the standard for how people should appear in the photograph. Film technology was built around this idea.

As a result, people with darker skin were never portrayed accurately and did not have a lot of detail to their features or their skin. A number of famous photographers boycotted by not using the film.

But it wasn’t until chocolate manufacturers and the furniture industries decided that Kodak Gold film was not showing their brown products in enough detail that Kodak was forced to change.

It took these big industries saying “we’re not going to use your film anymore” to spur the development of multicultural Shirley cards which included images of Asian, White, and Black women (a Latina was added later). That didn’t happen until 1995. By then, digital photography had already started to take off. Unfortunately, that advance built off of the original color film and still harbored some of the same issues.

So in addition to concerns about clinicians not recognizing a skin change in a darker-skinned person, if they do recognize it and do decide to photograph it, it just might not come out right. So then it’s possible that clinicians just decide to stop taking photos.

This is another example of structural racism – things that are just baked into the system about which people are unaware. I fear we’ll continue to perpetuate these unconscious biases with the development of augmented intelligence or various algorithms.

I think that this history – which I was unaware of – highlights what happens when White skin becomes the standard. It certainly explains the issue we’ve both seen of clinicians not recognizing erythema on dark skin.

That’s a big one. And I think it’s a big one because it’s a shared presenting sign of a lot of different rashes. It can also be a sign of a dermatologic emergency that requires rapid recognition and treatment. Erythema can be very subtle, especially in skin of color. It is one of the things that we use to grade severity of psoriasis, and as a result of it not being appreciated in people with darker skin, those patients have not been included in a lot of the clinical trials.

There has even been discussion of whether erythema is something we should deem to be an important finding in people with darker skin.

Maybe one of the problems is terminology. Erythema connotes pink or red coloration, and that does not really show up on dark skin as overtly.

Exactly. Emollient use is also different in people of color. So the “classic” scales of psoriasis often aren’t present in someone who uses a lot of lotion.

In addition to the different clinical appearance of many common skin conditions, cultural practices might be different in different groups, which may also alter your differential diagnoses and treatment recommendations – for instance, moisturizer use, shampooing frequency, or use of different hair styling products.

I totally agree. Hair is another big one. Identifying broken hairs, short hairs, texture changes, and variability in the size of the hair shaft is different in coiled, Black hair and is not really applicable to people with more textured hair patterns. People of different ethnicities and cultures do different things. Standards that we traditionally use, such as the hair-pull test, don’t work quite as well in different groups.

I think that speaks to the changes that we also need to make in educating both dermatologists and nondermatologists in diagnostic criteria and clinical findings.

Dermatology is the second least diverse specialty. And that means our experts – faculty, lecturers, mentors – are not likely to be people of color. You don’t know what you don’t know. You only have your own experiences. If you don’t have people who can explain why something may be different for a different group of people, you don’t have an opportunity to broaden your understanding. You and I noticed because we know what it’s like to have this type of hair. But it’s not something that other people who don’t share the same hair type would have the same perspective on.

It is even more reason to make sure that our dermatology workforce mirrors our population. About 3% of the dermatologists in the United States are Black; the numbers are equally bad for Latino and indigenous dermatologists. If you don’t have enough people in your immediate environment who can help broaden your perspective, that becomes a problem that can harm patients.

If we don’t have a diverse group of people in the field who are contributing to the literature, changing some of the ways that we think about practice, then everyone is just going to keep doing the wrong thing.

We need to build our evidence and pay more attention to the racial breakdown of patients included in studies. We are recognizing that we have blind spots but we don’t have people or data that can change that. If what we are publishing overrepresents a certain group, how will we ever learn to do things differently?

I recognize the fact that this is not a new idea. Others have worked on these issues for a long time. Your colleague, Susan Taylor, MD, a professor at University of Pennsylvania and a founder of the Skin of Color Society, used her energy and frustration about this issue and published a whole textbook on it: “Dermatology for Skin of Color.” When I tried to publish my first paper on this issue, I got a lot of pushback, but I’m happy that now it’s something that everyone is talking about. So just in the span of a couple of years, the acceptance of this idea has changed dramatically.

I hope that this is the start of sustainable, systemic changes that can have a real impact.

Let me ask a technical question. Is the excuse of not knowing how to photograph darker skin just that – an excuse? Or is that concern truly valid?

That’s a great question. There are certain techniques that one can employ. And yes, it can be more challenging if you are not used to taking photos of people with darker skin, but it certainly can be learned.

I think that an intelligent group of people who have faced things before that felt insurmountable could continue to push to figure out how to do it. But it is something that does require skills, and part of it is because there’s this bias built into the camera, so you have to make up for that.

I think every single dermatologist has that ability, and you just have to know that it’s worthwhile to do because your patient is that valuable.

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

A recent review looked at all articles describing skin manifestations associated with COVID-19 – 46 articles with a total of 130 clinical images – and found none that documented dermatologic conditions in people with dark skin. This was despite the disproportionate incidence of the disease in Black, Latino, and Native American/American Indian populations of color.

What’s going on? Temitayo Ogunleye, MD, an assistant professor of dermatology at the University of Pennsylvania, Philadelphia, spoke with lead investigator Jenna Lester, MD, a dermatologist and director of the Skin of Color Clinic at University of California, San Francisco, about the implications of her research.

Dr. Ogunleye: What prompted you to do this study in the first place?

Dr. Lester: It was actually driven by frustration. While we’re recognizing these COVID-related dermatologic manifestations, we’re still trying to figure out their clinical significance. We’ve learned what changes could be an early sign of infection and what might occur in people who are otherwise asymptomatic and should be tested. But in the process, we’re leaving out the group of people – dark-skinned populations – who are most heavily impacted by COVID. This is an injustice to the people who could benefit the most if found to have an early, visible sign of the disease on their skin. For example, pernio-like lesions and erythema, both of which have been seen in COVID patients, are harder to identify in darker skin.

As dermatologists, we know that the skin is the biggest organ and one that has the advantage of being visible. We partner with patients because they can see what we can see. We can explain what skin changes mean, and having examples to show them is really powerful. Because doctors typically respond best to numbers, I recognized that we needed data to prove that this lack of representation of persons of color in our COVID documentation was in fact true.

Can you tell us the key findings from your research?

We included any article that described the cutaneous manifestations of COVID – and also included a photograph – and was published over a period of 5 months. Then we categorized each image using the Fitzpatrick Skin Type Scale. We found that the majority of the photos were of people with light skin; there were no images at all of patients with dark skin, Fitzpatrick type V or VI. A handful, about 6%, depicted skin changes in patients with Fitzpatrick type IV skin.

Were you surprised by the findings?

No. I was not surprised at all, for a couple of reasons. First, many of the referrals that I had been getting to evaluate possible COVID manifestations were from primary care doctors. And as we both know, erythema, hyperpigmentation, and discoloration can be difficult for even a trained dermatologist to pick up on. So if these patients with skin changes potentially suggestive of COVID are presenting to their primary care doctor who could not determine what they were, perhaps because they had never seen them in someone with darker skin, it means those same clinicians are not likely to document these rashes. I suspect that a lot of these photos were sourced from primary care.

The other reason for my lack of surprise is that I have looked at this issue before. In a study I did in 2019 looking at images in dermatology textbooks, my coauthors and I found that there was a pretty dramatic underrepresentation of skin of color overall. Another analysis of images in core dermatology textbooks, published earlier this year by one of your colleagues at the University of Pennsylvania, Jules Lipoff, MD, showed that the percentage of images of dark skin ranged from as low as 4% to a high of about 18%.

So I wonder whether that makes us less likely to look for things in patients with darker skin, except for those conditions that we’re taught are more common in people with darker skin, like keloids, vitiligo, or certain types of hair loss. I wonder whether we just don’t think of other conditions because all the photos we ever see of psoriasis or rosacea, for example, are of people with lighter skin.

You bring up a good point about the cyclical nature of this process. If you don’t see skin conditions in darker skin, then you don’t know what to look for and so you never look for it.

Exactly. What if a Black patient says, for example: “This looks different on my skin; do you think this could be related to COVID?” And their doctor looks at their skin and says no. Not because it isn’t, but because they haven’t seen that before. Then they don’t take a picture of it and we’ll never know what that might have been.

The disturbing thing I have found is that there is an overrepresentation of dark skin in images of sexually transmitted infections. So based on what you are taught, you begin to create these powerful cognitive biases in your brain as a clinician and you start to put people in categories: “This person is more likely to get this because I’ve seen a lot of photos of it.”

Take the example of a 40ish Black woman with a cough who is presumed to have sarcoidosis, because we’ve all been taught that. But what we have not been taught, at least not as definitively, is that the highest prevalence of sarcoidosis is in Nordic countries, where there are not many Black people.

So these loops teach you things that don’t necessarily represent reality. We are taught to recognize patterns, but the patterns that we’ve created are not necessarily valid and carry the biases of the people who decided they were important for us to learn.
 

So the underrepresentation of persons of color in images depicting skin changes in COVID-19 is, in your perspective, a continuation of this pattern of bias?

I definitely think it is. It’s important to understand the history of photography and the development of color film in order to contextualize that question. Kodak Gold was one of the first color films made. To assist photographers, the company developed a Shirley card, which could be used for color balancing in developing this film. That card, which was distributed to film development labs across the country, depicted a fair-skinned White woman as the standard for how people should appear in the photograph. Film technology was built around this idea.

As a result, people with darker skin were never portrayed accurately and did not have a lot of detail to their features or their skin. A number of famous photographers boycotted by not using the film.

But it wasn’t until chocolate manufacturers and the furniture industries decided that Kodak Gold film was not showing their brown products in enough detail that Kodak was forced to change.

It took these big industries saying “we’re not going to use your film anymore” to spur the development of multicultural Shirley cards which included images of Asian, White, and Black women (a Latina was added later). That didn’t happen until 1995. By then, digital photography had already started to take off. Unfortunately, that advance built off of the original color film and still harbored some of the same issues.

So in addition to concerns about clinicians not recognizing a skin change in a darker-skinned person, if they do recognize it and do decide to photograph it, it just might not come out right. So then it’s possible that clinicians just decide to stop taking photos.

This is another example of structural racism – things that are just baked into the system about which people are unaware. I fear we’ll continue to perpetuate these unconscious biases with the development of augmented intelligence or various algorithms.

I think that this history – which I was unaware of – highlights what happens when White skin becomes the standard. It certainly explains the issue we’ve both seen of clinicians not recognizing erythema on dark skin.

That’s a big one. And I think it’s a big one because it’s a shared presenting sign of a lot of different rashes. It can also be a sign of a dermatologic emergency that requires rapid recognition and treatment. Erythema can be very subtle, especially in skin of color. It is one of the things that we use to grade severity of psoriasis, and as a result of it not being appreciated in people with darker skin, those patients have not been included in a lot of the clinical trials.

There has even been discussion of whether erythema is something we should deem to be an important finding in people with darker skin.

Maybe one of the problems is terminology. Erythema connotes pink or red coloration, and that does not really show up on dark skin as overtly.

Exactly. Emollient use is also different in people of color. So the “classic” scales of psoriasis often aren’t present in someone who uses a lot of lotion.

In addition to the different clinical appearance of many common skin conditions, cultural practices might be different in different groups, which may also alter your differential diagnoses and treatment recommendations – for instance, moisturizer use, shampooing frequency, or use of different hair styling products.

I totally agree. Hair is another big one. Identifying broken hairs, short hairs, texture changes, and variability in the size of the hair shaft is different in coiled, Black hair and is not really applicable to people with more textured hair patterns. People of different ethnicities and cultures do different things. Standards that we traditionally use, such as the hair-pull test, don’t work quite as well in different groups.

I think that speaks to the changes that we also need to make in educating both dermatologists and nondermatologists in diagnostic criteria and clinical findings.

Dermatology is the second least diverse specialty. And that means our experts – faculty, lecturers, mentors – are not likely to be people of color. You don’t know what you don’t know. You only have your own experiences. If you don’t have people who can explain why something may be different for a different group of people, you don’t have an opportunity to broaden your understanding. You and I noticed because we know what it’s like to have this type of hair. But it’s not something that other people who don’t share the same hair type would have the same perspective on.

It is even more reason to make sure that our dermatology workforce mirrors our population. About 3% of the dermatologists in the United States are Black; the numbers are equally bad for Latino and indigenous dermatologists. If you don’t have enough people in your immediate environment who can help broaden your perspective, that becomes a problem that can harm patients.

If we don’t have a diverse group of people in the field who are contributing to the literature, changing some of the ways that we think about practice, then everyone is just going to keep doing the wrong thing.

We need to build our evidence and pay more attention to the racial breakdown of patients included in studies. We are recognizing that we have blind spots but we don’t have people or data that can change that. If what we are publishing overrepresents a certain group, how will we ever learn to do things differently?

I recognize the fact that this is not a new idea. Others have worked on these issues for a long time. Your colleague, Susan Taylor, MD, a professor at University of Pennsylvania and a founder of the Skin of Color Society, used her energy and frustration about this issue and published a whole textbook on it: “Dermatology for Skin of Color.” When I tried to publish my first paper on this issue, I got a lot of pushback, but I’m happy that now it’s something that everyone is talking about. So just in the span of a couple of years, the acceptance of this idea has changed dramatically.

I hope that this is the start of sustainable, systemic changes that can have a real impact.

Let me ask a technical question. Is the excuse of not knowing how to photograph darker skin just that – an excuse? Or is that concern truly valid?

That’s a great question. There are certain techniques that one can employ. And yes, it can be more challenging if you are not used to taking photos of people with darker skin, but it certainly can be learned.

I think that an intelligent group of people who have faced things before that felt insurmountable could continue to push to figure out how to do it. But it is something that does require skills, and part of it is because there’s this bias built into the camera, so you have to make up for that.

I think every single dermatologist has that ability, and you just have to know that it’s worthwhile to do because your patient is that valuable.

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

U.S. regulators eventually could safely approve vaccines for COVID-19 if the process is kept free of political pressure regarding time lines, study protocols, and safety standards, expert witnesses told a House panel investigating the process on Wednesday.

The career staff of the Food and Drug Administration can be counted on to appropriately weigh whether a vaccine should be cleared for use in preventing COVID-19, witnesses, including Paul A. Offit, MD, of Children’s Hospital of Philadelphia, told the House Energy and Commerce Committee’s oversight and investigations panel.

FDA staffers would object to attempts by the Trump administration to rush a vaccine to the public without proper vetting, as would veteran federal researchers, including National Institutes of Health Director Francis S. Collins, MD, PhD, and Anthony S. Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, Offit said.

“If COVID-19 vaccines are released before they’re ready to be released, you will hear from these people, and you will also hear from people like Dr. Francis Collins and Tony Fauci, both of whom are trusted by the American public, as well as many other academicians and researchers who wouldn’t stand for this,” he said.

“The public is already nervous about these vaccines,” said Offit, who serves on key FDA and Centers for Disease Control and Prevention committees overseeing vaccine policy. “If trusted health officials stand up and decry a premature release, the celebration by the administration will be short-lived.”

Overly optimistic estimates about a potential approval can only serve to erode the public’s trust in these crucial vaccines, said another witness, Ashish K. Jha, MD, MPH, the dean of Brown University’s School of Public Health, in Providence, Rhode Island.

“All political leaders need to stop talking about things like time lines,” Jha told the lawmakers.

President Donald Trump has several times suggested that a COVID vaccine might be approved ahead of the November 3 election, where he faces a significant challenge from his Democratic rival, former Vice President Joe Biden.

In a Tuesday night debate with Biden, Trump again raised the idea of a quick approval. “Now we’re weeks away from a vaccine,” Trump said during the debate.

Trump’s estimates, though, are not in line with those offered by most firms involved with making vaccines. The most optimistic projections have come from Pfizer Inc. The drugmaker’s chief executive, Albert Bourla, has spoken about his company possibly having data to present to the FDA as early as late October about the safety and effectiveness of a vaccine.

In a September 8 interview with the Today show, Bourla said there was a 60% chance his company would meet that goal. In response to a question, he made it clear his comments applied to a potential Pfizer application, not an approval or release of a vaccine by that time.

In response to concerns about political pressures, the FDA in June issued guidance outlining what its staff would require for approval of a COVID-19 vaccine.
 

Pushback on politics

Another witness at the Wednesday hearing, Mark McClellan, MD, PhD, a former FDA commissioner (2002 – 2004), pushed back on objections to a potential release of further guidance from the agency.

“Some recent statements from the White House have implied that FDA’s plan to release additional written guidance on its expectations for emergency use authorization of a vaccine is unnecessarily raising the bar on regulatory standards for authorization,” said McClellan in his testimony for the House panel. “That is not the case.”

Instead, further FDA guidance would be a welcome form of feedback for the firms trying to develop COVID-19 vaccines, according to McClellan, who also serves on the board of directors for Johnson & Johnson. Johnson & Johnson is among the firms that have advanced a COVID-19 vaccine candidate to phase 3 testing. In his role as a director, he serves on the board’s regulatory compliance committee.

Along with politics, recent stumbles at FDA with emergency use authorizations (EUAs) of treatments for COVID-19 have eroded the public’s confidence in the agency, Jha told the House panel. The FDA approved hydroxychloroquine, a medicine promoted by Trump for use in COVID, under an EUA in March and then revoked this clearance in June.

Jha said the FDA’s most serious misstep was its handling of convalescent plasma, which was approved through an EUA on August 23 “in a highly advertised and widely televised announcement including the president.

“The announcement solidified in the public conversation the impression that, increasingly with this administration, politics are taking over trusted, nonpartisan scientific institutions,” he said in his testimony.

Approving a COVID-19 vaccine on the limited evidence through an EUA would mark a serious departure from FDA policy, according to Jha.

“While we sometimes accept a certain level of potential harm in experimental treatments for those who are severely ill, vaccines are given to healthy people and therefore need to have a substantially higher measure of safety and effectiveness,” he explained.

Jha said the FDA has only once before used this EUA approach for a vaccine. That was for a vaccine against inhaled anthrax and was mostly distributed to high-risk soldiers and civilians in war zones.

COVID-19, in contrast, is an infection that has changed lives around the world. The virus has contributed to more than 1 million deaths, including more than 200,000 in the United States, according to the World Health Organization.

Scientists are hoping vaccines will help curb this infection, although much of the future success of vaccines depends on how widely they are used, witnesses told the House panel.
 

Debate on approaches for vaccine effectiveness

In his testimony, Jha also noted concerns about COVID-19 vaccine trials. He included a reference to a Sept. 22 opinion article titled, “These Coronavirus Trials Don›t Answer the One Question We Need to Know,” which was written by Peter Doshi, PhD, of the University of Maryland School of Pharmacy, in Baltimore, and Eric Topol, MD, a professor of molecular medicine at Scripps Research in La Jolla, Calif. Topol is also editor in chief of Medscape.

Topol and Doshi questioned why the firms Moderna, Pfizer, and AstraZeneca structured their competing trials such that “a vaccine could meet the companies’ benchmark for success if it lowered the risk of mild Covid-19, but was never shown to reduce moderate or severe forms of the disease, or the risk of hospitalization, admissions to the intensive care unit or death.”

“To say a vaccine works should mean that most people no longer run the risk of getting seriously sick,” Topol and Doshi wrote. “That’s not what these trials will determine.”

There was disagreement about this point at the hearing. U.S. Representative Morgan Griffith (R-Va.) read the section of the Doshi-Topol article quoted above and asked one witness, Offit, to weigh in.

“Do you agree with those concerns? And either way, tell me why,” Griffith asked.

“I don’t agree,” Offit responded.

“I think it’s actually much harder to prevent asymptomatic infection or mildly symptomatic infection,” he said. “If you can prevent that, you are much more likely to prevent moderate to severe disease. So I think they have it backwards.”

But other researchers also question the approaches used with the current crop of COVID-19 vaccines.

“With the current protocols, it is conceivable that a vaccine might be considered effective – and eventually approved – based primarily on its ability to prevent mild cases alone,” wrote William Haseltine, PhD, president of the nonprofit ACCESS Health International, in a September 22 opinion article in the Washington Post titled: “Beware of COVID-19 Vaccine Trials Designed to Succeed From the Start.”
In an interview with Medscape Medical News on Wednesday, Haseltine said he maintains these concerns about the tests. Earlier in his career, he was a leader in HIV research through his lab at Harvard University in Cambridge, Massachusetts, and he subsequently led a biotech company, Human Genome Sciences.

He fears consumers will not get what they might expect from the vaccines being tested.

“What people care about is if this is going to keep them out of the hospital and will it keep them alive. And that’s not even part of this protocol,” Haseltine said.

This article first appeared on Medscape.com.

U.S. regulators eventually could safely approve vaccines for COVID-19 if the process is kept free of political pressure regarding time lines, study protocols, and safety standards, expert witnesses told a House panel investigating the process on Wednesday.

The career staff of the Food and Drug Administration can be counted on to appropriately weigh whether a vaccine should be cleared for use in preventing COVID-19, witnesses, including Paul A. Offit, MD, of Children’s Hospital of Philadelphia, told the House Energy and Commerce Committee’s oversight and investigations panel.

FDA staffers would object to attempts by the Trump administration to rush a vaccine to the public without proper vetting, as would veteran federal researchers, including National Institutes of Health Director Francis S. Collins, MD, PhD, and Anthony S. Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, Offit said.

“If COVID-19 vaccines are released before they’re ready to be released, you will hear from these people, and you will also hear from people like Dr. Francis Collins and Tony Fauci, both of whom are trusted by the American public, as well as many other academicians and researchers who wouldn’t stand for this,” he said.

“The public is already nervous about these vaccines,” said Offit, who serves on key FDA and Centers for Disease Control and Prevention committees overseeing vaccine policy. “If trusted health officials stand up and decry a premature release, the celebration by the administration will be short-lived.”

Overly optimistic estimates about a potential approval can only serve to erode the public’s trust in these crucial vaccines, said another witness, Ashish K. Jha, MD, MPH, the dean of Brown University’s School of Public Health, in Providence, Rhode Island.

“All political leaders need to stop talking about things like time lines,” Jha told the lawmakers.

President Donald Trump has several times suggested that a COVID vaccine might be approved ahead of the November 3 election, where he faces a significant challenge from his Democratic rival, former Vice President Joe Biden.

In a Tuesday night debate with Biden, Trump again raised the idea of a quick approval. “Now we’re weeks away from a vaccine,” Trump said during the debate.

Trump’s estimates, though, are not in line with those offered by most firms involved with making vaccines. The most optimistic projections have come from Pfizer Inc. The drugmaker’s chief executive, Albert Bourla, has spoken about his company possibly having data to present to the FDA as early as late October about the safety and effectiveness of a vaccine.

In a September 8 interview with the Today show, Bourla said there was a 60% chance his company would meet that goal. In response to a question, he made it clear his comments applied to a potential Pfizer application, not an approval or release of a vaccine by that time.

In response to concerns about political pressures, the FDA in June issued guidance outlining what its staff would require for approval of a COVID-19 vaccine.
 

Pushback on politics

Another witness at the Wednesday hearing, Mark McClellan, MD, PhD, a former FDA commissioner (2002 – 2004), pushed back on objections to a potential release of further guidance from the agency.

“Some recent statements from the White House have implied that FDA’s plan to release additional written guidance on its expectations for emergency use authorization of a vaccine is unnecessarily raising the bar on regulatory standards for authorization,” said McClellan in his testimony for the House panel. “That is not the case.”

Instead, further FDA guidance would be a welcome form of feedback for the firms trying to develop COVID-19 vaccines, according to McClellan, who also serves on the board of directors for Johnson & Johnson. Johnson & Johnson is among the firms that have advanced a COVID-19 vaccine candidate to phase 3 testing. In his role as a director, he serves on the board’s regulatory compliance committee.

Along with politics, recent stumbles at FDA with emergency use authorizations (EUAs) of treatments for COVID-19 have eroded the public’s confidence in the agency, Jha told the House panel. The FDA approved hydroxychloroquine, a medicine promoted by Trump for use in COVID, under an EUA in March and then revoked this clearance in June.

Jha said the FDA’s most serious misstep was its handling of convalescent plasma, which was approved through an EUA on August 23 “in a highly advertised and widely televised announcement including the president.

“The announcement solidified in the public conversation the impression that, increasingly with this administration, politics are taking over trusted, nonpartisan scientific institutions,” he said in his testimony.

Approving a COVID-19 vaccine on the limited evidence through an EUA would mark a serious departure from FDA policy, according to Jha.

“While we sometimes accept a certain level of potential harm in experimental treatments for those who are severely ill, vaccines are given to healthy people and therefore need to have a substantially higher measure of safety and effectiveness,” he explained.

Jha said the FDA has only once before used this EUA approach for a vaccine. That was for a vaccine against inhaled anthrax and was mostly distributed to high-risk soldiers and civilians in war zones.

COVID-19, in contrast, is an infection that has changed lives around the world. The virus has contributed to more than 1 million deaths, including more than 200,000 in the United States, according to the World Health Organization.

Scientists are hoping vaccines will help curb this infection, although much of the future success of vaccines depends on how widely they are used, witnesses told the House panel.
 

Debate on approaches for vaccine effectiveness

In his testimony, Jha also noted concerns about COVID-19 vaccine trials. He included a reference to a Sept. 22 opinion article titled, “These Coronavirus Trials Don›t Answer the One Question We Need to Know,” which was written by Peter Doshi, PhD, of the University of Maryland School of Pharmacy, in Baltimore, and Eric Topol, MD, a professor of molecular medicine at Scripps Research in La Jolla, Calif. Topol is also editor in chief of Medscape.

Topol and Doshi questioned why the firms Moderna, Pfizer, and AstraZeneca structured their competing trials such that “a vaccine could meet the companies’ benchmark for success if it lowered the risk of mild Covid-19, but was never shown to reduce moderate or severe forms of the disease, or the risk of hospitalization, admissions to the intensive care unit or death.”

“To say a vaccine works should mean that most people no longer run the risk of getting seriously sick,” Topol and Doshi wrote. “That’s not what these trials will determine.”

There was disagreement about this point at the hearing. U.S. Representative Morgan Griffith (R-Va.) read the section of the Doshi-Topol article quoted above and asked one witness, Offit, to weigh in.

“Do you agree with those concerns? And either way, tell me why,” Griffith asked.

“I don’t agree,” Offit responded.

“I think it’s actually much harder to prevent asymptomatic infection or mildly symptomatic infection,” he said. “If you can prevent that, you are much more likely to prevent moderate to severe disease. So I think they have it backwards.”

But other researchers also question the approaches used with the current crop of COVID-19 vaccines.

“With the current protocols, it is conceivable that a vaccine might be considered effective – and eventually approved – based primarily on its ability to prevent mild cases alone,” wrote William Haseltine, PhD, president of the nonprofit ACCESS Health International, in a September 22 opinion article in the Washington Post titled: “Beware of COVID-19 Vaccine Trials Designed to Succeed From the Start.”
In an interview with Medscape Medical News on Wednesday, Haseltine said he maintains these concerns about the tests. Earlier in his career, he was a leader in HIV research through his lab at Harvard University in Cambridge, Massachusetts, and he subsequently led a biotech company, Human Genome Sciences.

He fears consumers will not get what they might expect from the vaccines being tested.

“What people care about is if this is going to keep them out of the hospital and will it keep them alive. And that’s not even part of this protocol,” Haseltine said.

This article first appeared on Medscape.com.

U.S. regulators eventually could safely approve vaccines for COVID-19 if the process is kept free of political pressure regarding time lines, study protocols, and safety standards, expert witnesses told a House panel investigating the process on Wednesday.

The career staff of the Food and Drug Administration can be counted on to appropriately weigh whether a vaccine should be cleared for use in preventing COVID-19, witnesses, including Paul A. Offit, MD, of Children’s Hospital of Philadelphia, told the House Energy and Commerce Committee’s oversight and investigations panel.

FDA staffers would object to attempts by the Trump administration to rush a vaccine to the public without proper vetting, as would veteran federal researchers, including National Institutes of Health Director Francis S. Collins, MD, PhD, and Anthony S. Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, Offit said.

“If COVID-19 vaccines are released before they’re ready to be released, you will hear from these people, and you will also hear from people like Dr. Francis Collins and Tony Fauci, both of whom are trusted by the American public, as well as many other academicians and researchers who wouldn’t stand for this,” he said.

“The public is already nervous about these vaccines,” said Offit, who serves on key FDA and Centers for Disease Control and Prevention committees overseeing vaccine policy. “If trusted health officials stand up and decry a premature release, the celebration by the administration will be short-lived.”

Overly optimistic estimates about a potential approval can only serve to erode the public’s trust in these crucial vaccines, said another witness, Ashish K. Jha, MD, MPH, the dean of Brown University’s School of Public Health, in Providence, Rhode Island.

“All political leaders need to stop talking about things like time lines,” Jha told the lawmakers.

President Donald Trump has several times suggested that a COVID vaccine might be approved ahead of the November 3 election, where he faces a significant challenge from his Democratic rival, former Vice President Joe Biden.

In a Tuesday night debate with Biden, Trump again raised the idea of a quick approval. “Now we’re weeks away from a vaccine,” Trump said during the debate.

Trump’s estimates, though, are not in line with those offered by most firms involved with making vaccines. The most optimistic projections have come from Pfizer Inc. The drugmaker’s chief executive, Albert Bourla, has spoken about his company possibly having data to present to the FDA as early as late October about the safety and effectiveness of a vaccine.

In a September 8 interview with the Today show, Bourla said there was a 60% chance his company would meet that goal. In response to a question, he made it clear his comments applied to a potential Pfizer application, not an approval or release of a vaccine by that time.

In response to concerns about political pressures, the FDA in June issued guidance outlining what its staff would require for approval of a COVID-19 vaccine.
 

Pushback on politics

Another witness at the Wednesday hearing, Mark McClellan, MD, PhD, a former FDA commissioner (2002 – 2004), pushed back on objections to a potential release of further guidance from the agency.

“Some recent statements from the White House have implied that FDA’s plan to release additional written guidance on its expectations for emergency use authorization of a vaccine is unnecessarily raising the bar on regulatory standards for authorization,” said McClellan in his testimony for the House panel. “That is not the case.”

Instead, further FDA guidance would be a welcome form of feedback for the firms trying to develop COVID-19 vaccines, according to McClellan, who also serves on the board of directors for Johnson & Johnson. Johnson & Johnson is among the firms that have advanced a COVID-19 vaccine candidate to phase 3 testing. In his role as a director, he serves on the board’s regulatory compliance committee.

Along with politics, recent stumbles at FDA with emergency use authorizations (EUAs) of treatments for COVID-19 have eroded the public’s confidence in the agency, Jha told the House panel. The FDA approved hydroxychloroquine, a medicine promoted by Trump for use in COVID, under an EUA in March and then revoked this clearance in June.

Jha said the FDA’s most serious misstep was its handling of convalescent plasma, which was approved through an EUA on August 23 “in a highly advertised and widely televised announcement including the president.

“The announcement solidified in the public conversation the impression that, increasingly with this administration, politics are taking over trusted, nonpartisan scientific institutions,” he said in his testimony.

Approving a COVID-19 vaccine on the limited evidence through an EUA would mark a serious departure from FDA policy, according to Jha.

“While we sometimes accept a certain level of potential harm in experimental treatments for those who are severely ill, vaccines are given to healthy people and therefore need to have a substantially higher measure of safety and effectiveness,” he explained.

Jha said the FDA has only once before used this EUA approach for a vaccine. That was for a vaccine against inhaled anthrax and was mostly distributed to high-risk soldiers and civilians in war zones.

COVID-19, in contrast, is an infection that has changed lives around the world. The virus has contributed to more than 1 million deaths, including more than 200,000 in the United States, according to the World Health Organization.

Scientists are hoping vaccines will help curb this infection, although much of the future success of vaccines depends on how widely they are used, witnesses told the House panel.
 

Debate on approaches for vaccine effectiveness

In his testimony, Jha also noted concerns about COVID-19 vaccine trials. He included a reference to a Sept. 22 opinion article titled, “These Coronavirus Trials Don›t Answer the One Question We Need to Know,” which was written by Peter Doshi, PhD, of the University of Maryland School of Pharmacy, in Baltimore, and Eric Topol, MD, a professor of molecular medicine at Scripps Research in La Jolla, Calif. Topol is also editor in chief of Medscape.

Topol and Doshi questioned why the firms Moderna, Pfizer, and AstraZeneca structured their competing trials such that “a vaccine could meet the companies’ benchmark for success if it lowered the risk of mild Covid-19, but was never shown to reduce moderate or severe forms of the disease, or the risk of hospitalization, admissions to the intensive care unit or death.”

“To say a vaccine works should mean that most people no longer run the risk of getting seriously sick,” Topol and Doshi wrote. “That’s not what these trials will determine.”

There was disagreement about this point at the hearing. U.S. Representative Morgan Griffith (R-Va.) read the section of the Doshi-Topol article quoted above and asked one witness, Offit, to weigh in.

“Do you agree with those concerns? And either way, tell me why,” Griffith asked.

“I don’t agree,” Offit responded.

“I think it’s actually much harder to prevent asymptomatic infection or mildly symptomatic infection,” he said. “If you can prevent that, you are much more likely to prevent moderate to severe disease. So I think they have it backwards.”

But other researchers also question the approaches used with the current crop of COVID-19 vaccines.

“With the current protocols, it is conceivable that a vaccine might be considered effective – and eventually approved – based primarily on its ability to prevent mild cases alone,” wrote William Haseltine, PhD, president of the nonprofit ACCESS Health International, in a September 22 opinion article in the Washington Post titled: “Beware of COVID-19 Vaccine Trials Designed to Succeed From the Start.”
In an interview with Medscape Medical News on Wednesday, Haseltine said he maintains these concerns about the tests. Earlier in his career, he was a leader in HIV research through his lab at Harvard University in Cambridge, Massachusetts, and he subsequently led a biotech company, Human Genome Sciences.

He fears consumers will not get what they might expect from the vaccines being tested.

“What people care about is if this is going to keep them out of the hospital and will it keep them alive. And that’s not even part of this protocol,” Haseltine said.

This article first appeared on Medscape.com.

Adding apatinib to gefitinib as first-line treatment improved progression-free survival (PFS) but increased toxicity in patients with advanced, epidermal growth factor receptor (EGFR)–mutant non–small cell lung cancer (NSCLC) in the ACTIVE trial.

ACTIVE is the first phase 3 trial of an oral vascular epidermal growth factor receptor–2 (VEGFR2) tyrosine kinase inhibitor (TKI) added to an EGFR-TKI as first-line therapy in this population, according to Li Zhang, MD, of Sun Yat-sen University Cancer Center in Guangzhou, China.

Dr. Zhang presented results from ACTIVE at the European Society for Medical Oncology Virtual Congress 2020.

“This dual oral regimen will provide more convenient treatment for patients who require long-term administration,” Dr. Zhang said. He added that apatinib plus gefitinib “is expected to become a new first-line treatment option for EGFR-mutant NSCLC.”

A discussant for the ACTIVE study was less optimistic, however, noting that the regimen proved tough to tolerate for some patients, and the PFS benefit may not translate to overall survival.
 

Study rationale and details

Sensitizing EGFR mutations occur in about 10% of White patients and up to 50% of Asian patients, Dr. Zhang noted. Unfortunately, most patients progress after first-line treatment with EGFR-TKIs because of acquired resistance.

Blocking VEGF receptor pathways has been shown to enhance EGFR-TKIs in EGFR-mutated NSCLC, and pilot study results have shown apatinib – an oral VEGFR2–TKI – to be safe and well-tolerated with promising efficacy in combination with gefitinib, Dr. Zhang added.

To expand upon those results, he and his colleagues tested apatinib with gefitinib in the phase 3, double-blind, placebo-controlled ACTIVE trial (CTONG1706).

The trial included 313 patients (median age, 58.5 years) with locally advanced, metastatic, or recurrent nonsquamous NSCLC. All were chemotherapy-naive and EGFR mutation-positive (exon 19 deletion or exon 21 L858R).

Patients were randomized 1:1 to first-line apatinib at 500 mg daily plus gefitinib at 250 mg daily (n = 157) or placebo plus gefitinib at 250 mg daily (n = 156) until progressive disease or unacceptable toxicity.
 

Efficacy and safety

The primary endpoint was PFS by independent review. The median follow-up was 15.8 months.

The median PFS was 13.7 months in the apatinib group and 10.2 months in the placebo group (hazard ratio, 0.71; P = .0189).

Objective response rates were similar for both groups – 77.1% with apatinib and 73.7% with placebo. However, depth of response ≥30% and depth of response ≥50% both favored the apatinib arm – 89.2% versus 79.5% for ≥ 30% (P = .0209) and 64.3% versus 52.6% for ≥50% (P = .0238).

In addition, the median duration of response was longer for the apatinib group – 12.9 months versus 9.3 months (HR, 0.64; P = .005).

Exploratory biomarker analyses showed the benefit of apatinib was more common in patients with TP53 exon 8 mutations.

The rate of grade 3 or higher treatment-emergent adverse events was 84.1% in the apatinib arm and 37.7% in the placebo arm. Diarrhea (73.2%) and hypertension (68.2%) were the most common treatment-emergent adverse events in the apatinib group.

Dose interruptions were more common in the apatinib group (59.5% vs. 22.7%) as were dose reductions (48.4% vs. 4.5%). However, treatment discontinuations attributable to treatment-emergent adverse events were few in both arms (5.1% in the apatinib arm and 3.2% in the placebo arm).
 

Cause for hesitation

“VEGFR-TKIs have not yet found a solid home in lung cancer,” said study discussant Lecia V. Sequist, MD, of Massachusetts General Hospital in Boston.

Listing 10 VEGFR-TKIs, Dr. Sequist noted: “None of them have changed practice.”

She added that, while an all-oral regimen is appealing, the benefit of adding apatinib to gefitinib was modest, and the regimen was “fairly difficult” to tolerate. “The PFS with apatinib plus gefitinib is well below what we see with other EGFR/VEGF first-line studies,” she said.

Dr. Sequist also observed that most studies have shown a PFS benefit but no overall survival benefit. “That, in combination with the toxicity, makes me a little hesitant about this regimen. The role of VEGF remains unclear in EGFR mutation–positive lung cancer in 2020,” she concluded.

The ACTIVE study was funded by Jiangsu HengRui Medicine, the Chinese Thoracic Oncology Group, and grants from Sun Yat-sen University and the National Key R&D Program of China. Dr. Zhang disclosed relationships with AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Pfizer, and Roche. Dr. Sequist disclosed relationships with AstraZeneca, Bristol-Myers Squibb, Blueprint Medicines, and many other companies.

SOURCE: Zhang L et al. ESMO 2020, Abstract LBA50.

Adding apatinib to gefitinib as first-line treatment improved progression-free survival (PFS) but increased toxicity in patients with advanced, epidermal growth factor receptor (EGFR)–mutant non–small cell lung cancer (NSCLC) in the ACTIVE trial.

ACTIVE is the first phase 3 trial of an oral vascular epidermal growth factor receptor–2 (VEGFR2) tyrosine kinase inhibitor (TKI) added to an EGFR-TKI as first-line therapy in this population, according to Li Zhang, MD, of Sun Yat-sen University Cancer Center in Guangzhou, China.

Dr. Zhang presented results from ACTIVE at the European Society for Medical Oncology Virtual Congress 2020.

“This dual oral regimen will provide more convenient treatment for patients who require long-term administration,” Dr. Zhang said. He added that apatinib plus gefitinib “is expected to become a new first-line treatment option for EGFR-mutant NSCLC.”

A discussant for the ACTIVE study was less optimistic, however, noting that the regimen proved tough to tolerate for some patients, and the PFS benefit may not translate to overall survival.
 

Study rationale and details

Sensitizing EGFR mutations occur in about 10% of White patients and up to 50% of Asian patients, Dr. Zhang noted. Unfortunately, most patients progress after first-line treatment with EGFR-TKIs because of acquired resistance.

Blocking VEGF receptor pathways has been shown to enhance EGFR-TKIs in EGFR-mutated NSCLC, and pilot study results have shown apatinib – an oral VEGFR2–TKI – to be safe and well-tolerated with promising efficacy in combination with gefitinib, Dr. Zhang added.

To expand upon those results, he and his colleagues tested apatinib with gefitinib in the phase 3, double-blind, placebo-controlled ACTIVE trial (CTONG1706).

The trial included 313 patients (median age, 58.5 years) with locally advanced, metastatic, or recurrent nonsquamous NSCLC. All were chemotherapy-naive and EGFR mutation-positive (exon 19 deletion or exon 21 L858R).

Patients were randomized 1:1 to first-line apatinib at 500 mg daily plus gefitinib at 250 mg daily (n = 157) or placebo plus gefitinib at 250 mg daily (n = 156) until progressive disease or unacceptable toxicity.
 

Efficacy and safety

The primary endpoint was PFS by independent review. The median follow-up was 15.8 months.

The median PFS was 13.7 months in the apatinib group and 10.2 months in the placebo group (hazard ratio, 0.71; P = .0189).

Objective response rates were similar for both groups – 77.1% with apatinib and 73.7% with placebo. However, depth of response ≥30% and depth of response ≥50% both favored the apatinib arm – 89.2% versus 79.5% for ≥ 30% (P = .0209) and 64.3% versus 52.6% for ≥50% (P = .0238).

In addition, the median duration of response was longer for the apatinib group – 12.9 months versus 9.3 months (HR, 0.64; P = .005).

Exploratory biomarker analyses showed the benefit of apatinib was more common in patients with TP53 exon 8 mutations.

The rate of grade 3 or higher treatment-emergent adverse events was 84.1% in the apatinib arm and 37.7% in the placebo arm. Diarrhea (73.2%) and hypertension (68.2%) were the most common treatment-emergent adverse events in the apatinib group.

Dose interruptions were more common in the apatinib group (59.5% vs. 22.7%) as were dose reductions (48.4% vs. 4.5%). However, treatment discontinuations attributable to treatment-emergent adverse events were few in both arms (5.1% in the apatinib arm and 3.2% in the placebo arm).
 

Cause for hesitation

“VEGFR-TKIs have not yet found a solid home in lung cancer,” said study discussant Lecia V. Sequist, MD, of Massachusetts General Hospital in Boston.

Listing 10 VEGFR-TKIs, Dr. Sequist noted: “None of them have changed practice.”

She added that, while an all-oral regimen is appealing, the benefit of adding apatinib to gefitinib was modest, and the regimen was “fairly difficult” to tolerate. “The PFS with apatinib plus gefitinib is well below what we see with other EGFR/VEGF first-line studies,” she said.

Dr. Sequist also observed that most studies have shown a PFS benefit but no overall survival benefit. “That, in combination with the toxicity, makes me a little hesitant about this regimen. The role of VEGF remains unclear in EGFR mutation–positive lung cancer in 2020,” she concluded.

The ACTIVE study was funded by Jiangsu HengRui Medicine, the Chinese Thoracic Oncology Group, and grants from Sun Yat-sen University and the National Key R&D Program of China. Dr. Zhang disclosed relationships with AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Pfizer, and Roche. Dr. Sequist disclosed relationships with AstraZeneca, Bristol-Myers Squibb, Blueprint Medicines, and many other companies.

SOURCE: Zhang L et al. ESMO 2020, Abstract LBA50.

Adding apatinib to gefitinib as first-line treatment improved progression-free survival (PFS) but increased toxicity in patients with advanced, epidermal growth factor receptor (EGFR)–mutant non–small cell lung cancer (NSCLC) in the ACTIVE trial.

ACTIVE is the first phase 3 trial of an oral vascular epidermal growth factor receptor–2 (VEGFR2) tyrosine kinase inhibitor (TKI) added to an EGFR-TKI as first-line therapy in this population, according to Li Zhang, MD, of Sun Yat-sen University Cancer Center in Guangzhou, China.

Dr. Zhang presented results from ACTIVE at the European Society for Medical Oncology Virtual Congress 2020.

“This dual oral regimen will provide more convenient treatment for patients who require long-term administration,” Dr. Zhang said. He added that apatinib plus gefitinib “is expected to become a new first-line treatment option for EGFR-mutant NSCLC.”

A discussant for the ACTIVE study was less optimistic, however, noting that the regimen proved tough to tolerate for some patients, and the PFS benefit may not translate to overall survival.
 

Study rationale and details

Sensitizing EGFR mutations occur in about 10% of White patients and up to 50% of Asian patients, Dr. Zhang noted. Unfortunately, most patients progress after first-line treatment with EGFR-TKIs because of acquired resistance.

Blocking VEGF receptor pathways has been shown to enhance EGFR-TKIs in EGFR-mutated NSCLC, and pilot study results have shown apatinib – an oral VEGFR2–TKI – to be safe and well-tolerated with promising efficacy in combination with gefitinib, Dr. Zhang added.

To expand upon those results, he and his colleagues tested apatinib with gefitinib in the phase 3, double-blind, placebo-controlled ACTIVE trial (CTONG1706).

The trial included 313 patients (median age, 58.5 years) with locally advanced, metastatic, or recurrent nonsquamous NSCLC. All were chemotherapy-naive and EGFR mutation-positive (exon 19 deletion or exon 21 L858R).

Patients were randomized 1:1 to first-line apatinib at 500 mg daily plus gefitinib at 250 mg daily (n = 157) or placebo plus gefitinib at 250 mg daily (n = 156) until progressive disease or unacceptable toxicity.
 

Efficacy and safety

The primary endpoint was PFS by independent review. The median follow-up was 15.8 months.

The median PFS was 13.7 months in the apatinib group and 10.2 months in the placebo group (hazard ratio, 0.71; P = .0189).

Objective response rates were similar for both groups – 77.1% with apatinib and 73.7% with placebo. However, depth of response ≥30% and depth of response ≥50% both favored the apatinib arm – 89.2% versus 79.5% for ≥ 30% (P = .0209) and 64.3% versus 52.6% for ≥50% (P = .0238).

In addition, the median duration of response was longer for the apatinib group – 12.9 months versus 9.3 months (HR, 0.64; P = .005).

Exploratory biomarker analyses showed the benefit of apatinib was more common in patients with TP53 exon 8 mutations.

The rate of grade 3 or higher treatment-emergent adverse events was 84.1% in the apatinib arm and 37.7% in the placebo arm. Diarrhea (73.2%) and hypertension (68.2%) were the most common treatment-emergent adverse events in the apatinib group.

Dose interruptions were more common in the apatinib group (59.5% vs. 22.7%) as were dose reductions (48.4% vs. 4.5%). However, treatment discontinuations attributable to treatment-emergent adverse events were few in both arms (5.1% in the apatinib arm and 3.2% in the placebo arm).
 

Cause for hesitation

“VEGFR-TKIs have not yet found a solid home in lung cancer,” said study discussant Lecia V. Sequist, MD, of Massachusetts General Hospital in Boston.

Listing 10 VEGFR-TKIs, Dr. Sequist noted: “None of them have changed practice.”

She added that, while an all-oral regimen is appealing, the benefit of adding apatinib to gefitinib was modest, and the regimen was “fairly difficult” to tolerate. “The PFS with apatinib plus gefitinib is well below what we see with other EGFR/VEGF first-line studies,” she said.

Dr. Sequist also observed that most studies have shown a PFS benefit but no overall survival benefit. “That, in combination with the toxicity, makes me a little hesitant about this regimen. The role of VEGF remains unclear in EGFR mutation–positive lung cancer in 2020,” she concluded.

The ACTIVE study was funded by Jiangsu HengRui Medicine, the Chinese Thoracic Oncology Group, and grants from Sun Yat-sen University and the National Key R&D Program of China. Dr. Zhang disclosed relationships with AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Pfizer, and Roche. Dr. Sequist disclosed relationships with AstraZeneca, Bristol-Myers Squibb, Blueprint Medicines, and many other companies.

SOURCE: Zhang L et al. ESMO 2020, Abstract LBA50.

Clarence Troutman survived a 2-month hospital stay with COVID-19, then went home in early June. But he’s far from over the disease, still suffering from limited endurance, shortness of breath and hands that can be stiff and swollen.

“Before COVID, I was a 59-year-old, relatively healthy man,” said the broadband technician from Denver. “If I had to say where I’m at now, I’d say about 50% of where I was, but when I first went home, I was at 20%.”

He credits much of his progress to the “motivation and education” gleaned from a new program for post-COVID patients at the University of Colorado at Denver, Aurora, one of a small but growing number of clinics aimed at treating and studying those who have had the unpredictable coronavirus.

As the election nears, much attention is focused on daily infection numbers or the climbing death toll, but another measure matters: Patients who survive but continue to wrestle with a range of physical or mental effects, including lung damage, heart or neurologic concerns, anxiety, and depression.

“We need to think about how we’re going to provide care for patients who may be recovering for years after the virus,” said Sarah Jolley, MD, a pulmonologist with UCHealth University of Colorado Hospital and director of UCHealth’s Post-Covid Clinic, where Mr. Troutman is seen.

That need has jump-started post-COVID clinics, which bring together a range of specialists into a one-stop shop.

One of the first and largest such clinics is at Mount Sinai in New York City, but programs have also launched at the University of California,San Francisco; Stanford (Calif.) University Medical Center; and the University of Pennsylvania, Philadelphia. The Cleveland Clinic plans to open one early next year. And it’s not just academic medical centers: St. John’s Well Child and Family Center, part of a network of community clinics in south central Los Angeles, said this month it aims to test thousands of its patients who were diagnosed with COVID-19 since March for long-term effects.

The general idea is to bring together medical professionals across a broad spectrum, including physicians who specialize in lung disorders, heart issues, and brain and spinal cord problems. Mental health specialists are also involved, along with social workers and pharmacists. Many of the centers also do research studies, aiming to better understand why the virus hits certain patients so hard.

“Some of our patients, even those on a ventilator on death’s door, will come out remarkably unscathed,” said Lekshmi Santhosh, MD, an assistant professor of pulmonary critical care and a leader of the post-COVID program at UCSF, called the OPTIMAL clinic. “Others, even those who were never hospitalized, have disabling fatigue, ongoing chest pain, and shortness of breath, and there’s a whole spectrum in between.”
 

‘Staggering’ medical need

It’s too early to know how long the persistent medical effects and symptoms will linger, or to make accurate estimates on the percentage of patients affected.

Some early studies are sobering. An Austrian report released this month found that 76 of the first 86 patients studied had evidence of lung damage 6 weeks after hospital discharge, but that dropped to 48 patients at 12 weeks.

Some researchers and clinics say about 10% of U.S. COVID patients they see may have longer-running effects, said Zijian Chen, MD, medical director of the Center for Post-COVID Care at Mount Sinai, which has enrolled 400 patients so far.

If that estimate is correct – and Dr. Chen emphasized that more research is needed to make sure – it translates to patients entering the medical system in droves, often with multiple issues.

How health systems and insurers respond will be key, he said. More than 6.5 million U.S. residents have tested positive for the disease. If fewer than 10% – say 500,000 – already have long-lasting symptoms, “that number is staggering,” Dr. Chen said. “How much medical care will be needed for that?”

Though start-up costs could be a hurdle, the clinics themselves may eventually draw much-needed revenue to medical centers by attracting patients, many of whom have insurance to cover some or all of the cost of repeated visits.

Dr. Chen said the specialized centers can help lower health spending by providing more cost effective, coordinated care that avoids duplicative testing a patient might otherwise undergo.

“We’ve seen patients that when they come in, they’ve already had four MRI or CT scans and a stack of bloodwork,” he said.

The program consolidates those earlier results and determines if any additional testing is needed. Sometimes the answer to what’s causing patients’ long-lasting symptoms remains elusive. One problem for patients seeking help outside of dedicated clinics is that when there is no clear cause for their condition, they may be told the symptoms are imagined.

“I believe in the patients,” said Dr. Chen.

About half the clinic’s patients have received test results showing damage, said Dr. Chen, an endocrinologist and internal medicine physician. For those patients, the clinic can develop a treatment plan. But, frustratingly, the other half have inconclusive test results yet exhibit a range of symptoms.

“That makes it more difficult to treat,” said Dr. Chen.

Experts see parallels to a push in the past decade to establish special clinics to treat patients released from ICU wards, who may have problems related to long-term bed rest or the delirium many experience while hospitalized. Some of the current post-COVID clinics are modeled after the post-ICU clinics or are expanded versions of them.

The ICU Recovery Center at Vanderbilt University Medical Center, Nashville, Tenn., for instance, which opened in 2012, is accepting post-COVID patients.

There are about a dozen post-ICU clinics nationally, some of which are also now working with COVID patients, said James Jackson, director of long-term outcomes at the Vanderbilt center. In addition, he’s heard of at least another dozen post-COVID centers in development.

The centers generally do an initial assessment a few weeks after a patient is diagnosed or discharged from the hospital, often by video call. Check-in and repeat visits are scheduled every month or so after that.

“In an ideal world, with these post-COVID clinics, you can identify the patients and get them into rehab,” he said. “Even if the primary thing these clinics did was to say to patients: ‘This is real, it is not all in your head,’ that impact would be important.”
 

A question of feasibility

Financing is the largest obstacle, program proponents said. Many hospitals lost substantial revenue to canceled elective procedures during stay-at-home periods.

“So, it’s not a great time to be pitching a new activity that requires a start-up subsidy,” said Glenn Melnick, PhD, a professor of health economics at the University of Southern California.

At UCSF, a select group of faculty members staff the post-COVID clinics and some mental health professionals volunteer their time, said Dr. Santhosh.

Dr. Chen said he was able to recruit team members and support staff from the ranks of those whose elective patient caseload had dropped.

Dr. Jackson said unfortunately there’s not been enough research into the cost-and-clinical effectiveness of post-ICU centers.

“In the early days, there may have been questions about how much value does this add,” he noted. “Now, the question is not so much is it a good idea, but is it feasible?”

Right now, the post-COVID centers are foremost a research effort, said Len Nichols, an economist and nonresident fellow at the Urban Institute. “If these guys get good at treating long-term symptoms, that’s good for all of us. There’s not enough patients to make it a business model yet, but if they become the place to go when you get it, it could become a business model for some of the elite institutions.”

Kaiser Health News is a nonprofit news service covering health issues. It is an editorially independent program of KFF (Kaiser Family Foundation), which is not affiliated with Kaiser Permanente.

Clarence Troutman survived a 2-month hospital stay with COVID-19, then went home in early June. But he’s far from over the disease, still suffering from limited endurance, shortness of breath and hands that can be stiff and swollen.

“Before COVID, I was a 59-year-old, relatively healthy man,” said the broadband technician from Denver. “If I had to say where I’m at now, I’d say about 50% of where I was, but when I first went home, I was at 20%.”

He credits much of his progress to the “motivation and education” gleaned from a new program for post-COVID patients at the University of Colorado at Denver, Aurora, one of a small but growing number of clinics aimed at treating and studying those who have had the unpredictable coronavirus.

As the election nears, much attention is focused on daily infection numbers or the climbing death toll, but another measure matters: Patients who survive but continue to wrestle with a range of physical or mental effects, including lung damage, heart or neurologic concerns, anxiety, and depression.

“We need to think about how we’re going to provide care for patients who may be recovering for years after the virus,” said Sarah Jolley, MD, a pulmonologist with UCHealth University of Colorado Hospital and director of UCHealth’s Post-Covid Clinic, where Mr. Troutman is seen.

That need has jump-started post-COVID clinics, which bring together a range of specialists into a one-stop shop.

One of the first and largest such clinics is at Mount Sinai in New York City, but programs have also launched at the University of California,San Francisco; Stanford (Calif.) University Medical Center; and the University of Pennsylvania, Philadelphia. The Cleveland Clinic plans to open one early next year. And it’s not just academic medical centers: St. John’s Well Child and Family Center, part of a network of community clinics in south central Los Angeles, said this month it aims to test thousands of its patients who were diagnosed with COVID-19 since March for long-term effects.

The general idea is to bring together medical professionals across a broad spectrum, including physicians who specialize in lung disorders, heart issues, and brain and spinal cord problems. Mental health specialists are also involved, along with social workers and pharmacists. Many of the centers also do research studies, aiming to better understand why the virus hits certain patients so hard.

“Some of our patients, even those on a ventilator on death’s door, will come out remarkably unscathed,” said Lekshmi Santhosh, MD, an assistant professor of pulmonary critical care and a leader of the post-COVID program at UCSF, called the OPTIMAL clinic. “Others, even those who were never hospitalized, have disabling fatigue, ongoing chest pain, and shortness of breath, and there’s a whole spectrum in between.”
 

‘Staggering’ medical need

It’s too early to know how long the persistent medical effects and symptoms will linger, or to make accurate estimates on the percentage of patients affected.

Some early studies are sobering. An Austrian report released this month found that 76 of the first 86 patients studied had evidence of lung damage 6 weeks after hospital discharge, but that dropped to 48 patients at 12 weeks.

Some researchers and clinics say about 10% of U.S. COVID patients they see may have longer-running effects, said Zijian Chen, MD, medical director of the Center for Post-COVID Care at Mount Sinai, which has enrolled 400 patients so far.

If that estimate is correct – and Dr. Chen emphasized that more research is needed to make sure – it translates to patients entering the medical system in droves, often with multiple issues.

How health systems and insurers respond will be key, he said. More than 6.5 million U.S. residents have tested positive for the disease. If fewer than 10% – say 500,000 – already have long-lasting symptoms, “that number is staggering,” Dr. Chen said. “How much medical care will be needed for that?”

Though start-up costs could be a hurdle, the clinics themselves may eventually draw much-needed revenue to medical centers by attracting patients, many of whom have insurance to cover some or all of the cost of repeated visits.

Dr. Chen said the specialized centers can help lower health spending by providing more cost effective, coordinated care that avoids duplicative testing a patient might otherwise undergo.

“We’ve seen patients that when they come in, they’ve already had four MRI or CT scans and a stack of bloodwork,” he said.

The program consolidates those earlier results and determines if any additional testing is needed. Sometimes the answer to what’s causing patients’ long-lasting symptoms remains elusive. One problem for patients seeking help outside of dedicated clinics is that when there is no clear cause for their condition, they may be told the symptoms are imagined.

“I believe in the patients,” said Dr. Chen.

About half the clinic’s patients have received test results showing damage, said Dr. Chen, an endocrinologist and internal medicine physician. For those patients, the clinic can develop a treatment plan. But, frustratingly, the other half have inconclusive test results yet exhibit a range of symptoms.

“That makes it more difficult to treat,” said Dr. Chen.

Experts see parallels to a push in the past decade to establish special clinics to treat patients released from ICU wards, who may have problems related to long-term bed rest or the delirium many experience while hospitalized. Some of the current post-COVID clinics are modeled after the post-ICU clinics or are expanded versions of them.

The ICU Recovery Center at Vanderbilt University Medical Center, Nashville, Tenn., for instance, which opened in 2012, is accepting post-COVID patients.

There are about a dozen post-ICU clinics nationally, some of which are also now working with COVID patients, said James Jackson, director of long-term outcomes at the Vanderbilt center. In addition, he’s heard of at least another dozen post-COVID centers in development.

The centers generally do an initial assessment a few weeks after a patient is diagnosed or discharged from the hospital, often by video call. Check-in and repeat visits are scheduled every month or so after that.

“In an ideal world, with these post-COVID clinics, you can identify the patients and get them into rehab,” he said. “Even if the primary thing these clinics did was to say to patients: ‘This is real, it is not all in your head,’ that impact would be important.”
 

A question of feasibility

Financing is the largest obstacle, program proponents said. Many hospitals lost substantial revenue to canceled elective procedures during stay-at-home periods.

“So, it’s not a great time to be pitching a new activity that requires a start-up subsidy,” said Glenn Melnick, PhD, a professor of health economics at the University of Southern California.

At UCSF, a select group of faculty members staff the post-COVID clinics and some mental health professionals volunteer their time, said Dr. Santhosh.

Dr. Chen said he was able to recruit team members and support staff from the ranks of those whose elective patient caseload had dropped.

Dr. Jackson said unfortunately there’s not been enough research into the cost-and-clinical effectiveness of post-ICU centers.

“In the early days, there may have been questions about how much value does this add,” he noted. “Now, the question is not so much is it a good idea, but is it feasible?”

Right now, the post-COVID centers are foremost a research effort, said Len Nichols, an economist and nonresident fellow at the Urban Institute. “If these guys get good at treating long-term symptoms, that’s good for all of us. There’s not enough patients to make it a business model yet, but if they become the place to go when you get it, it could become a business model for some of the elite institutions.”

Kaiser Health News is a nonprofit news service covering health issues. It is an editorially independent program of KFF (Kaiser Family Foundation), which is not affiliated with Kaiser Permanente.

Clarence Troutman survived a 2-month hospital stay with COVID-19, then went home in early June. But he’s far from over the disease, still suffering from limited endurance, shortness of breath and hands that can be stiff and swollen.

“Before COVID, I was a 59-year-old, relatively healthy man,” said the broadband technician from Denver. “If I had to say where I’m at now, I’d say about 50% of where I was, but when I first went home, I was at 20%.”

He credits much of his progress to the “motivation and education” gleaned from a new program for post-COVID patients at the University of Colorado at Denver, Aurora, one of a small but growing number of clinics aimed at treating and studying those who have had the unpredictable coronavirus.

As the election nears, much attention is focused on daily infection numbers or the climbing death toll, but another measure matters: Patients who survive but continue to wrestle with a range of physical or mental effects, including lung damage, heart or neurologic concerns, anxiety, and depression.

“We need to think about how we’re going to provide care for patients who may be recovering for years after the virus,” said Sarah Jolley, MD, a pulmonologist with UCHealth University of Colorado Hospital and director of UCHealth’s Post-Covid Clinic, where Mr. Troutman is seen.

That need has jump-started post-COVID clinics, which bring together a range of specialists into a one-stop shop.

One of the first and largest such clinics is at Mount Sinai in New York City, but programs have also launched at the University of California,San Francisco; Stanford (Calif.) University Medical Center; and the University of Pennsylvania, Philadelphia. The Cleveland Clinic plans to open one early next year. And it’s not just academic medical centers: St. John’s Well Child and Family Center, part of a network of community clinics in south central Los Angeles, said this month it aims to test thousands of its patients who were diagnosed with COVID-19 since March for long-term effects.

The general idea is to bring together medical professionals across a broad spectrum, including physicians who specialize in lung disorders, heart issues, and brain and spinal cord problems. Mental health specialists are also involved, along with social workers and pharmacists. Many of the centers also do research studies, aiming to better understand why the virus hits certain patients so hard.

“Some of our patients, even those on a ventilator on death’s door, will come out remarkably unscathed,” said Lekshmi Santhosh, MD, an assistant professor of pulmonary critical care and a leader of the post-COVID program at UCSF, called the OPTIMAL clinic. “Others, even those who were never hospitalized, have disabling fatigue, ongoing chest pain, and shortness of breath, and there’s a whole spectrum in between.”
 

‘Staggering’ medical need

It’s too early to know how long the persistent medical effects and symptoms will linger, or to make accurate estimates on the percentage of patients affected.

Some early studies are sobering. An Austrian report released this month found that 76 of the first 86 patients studied had evidence of lung damage 6 weeks after hospital discharge, but that dropped to 48 patients at 12 weeks.

Some researchers and clinics say about 10% of U.S. COVID patients they see may have longer-running effects, said Zijian Chen, MD, medical director of the Center for Post-COVID Care at Mount Sinai, which has enrolled 400 patients so far.

If that estimate is correct – and Dr. Chen emphasized that more research is needed to make sure – it translates to patients entering the medical system in droves, often with multiple issues.

How health systems and insurers respond will be key, he said. More than 6.5 million U.S. residents have tested positive for the disease. If fewer than 10% – say 500,000 – already have long-lasting symptoms, “that number is staggering,” Dr. Chen said. “How much medical care will be needed for that?”

Though start-up costs could be a hurdle, the clinics themselves may eventually draw much-needed revenue to medical centers by attracting patients, many of whom have insurance to cover some or all of the cost of repeated visits.

Dr. Chen said the specialized centers can help lower health spending by providing more cost effective, coordinated care that avoids duplicative testing a patient might otherwise undergo.

“We’ve seen patients that when they come in, they’ve already had four MRI or CT scans and a stack of bloodwork,” he said.

The program consolidates those earlier results and determines if any additional testing is needed. Sometimes the answer to what’s causing patients’ long-lasting symptoms remains elusive. One problem for patients seeking help outside of dedicated clinics is that when there is no clear cause for their condition, they may be told the symptoms are imagined.

“I believe in the patients,” said Dr. Chen.

About half the clinic’s patients have received test results showing damage, said Dr. Chen, an endocrinologist and internal medicine physician. For those patients, the clinic can develop a treatment plan. But, frustratingly, the other half have inconclusive test results yet exhibit a range of symptoms.

“That makes it more difficult to treat,” said Dr. Chen.

Experts see parallels to a push in the past decade to establish special clinics to treat patients released from ICU wards, who may have problems related to long-term bed rest or the delirium many experience while hospitalized. Some of the current post-COVID clinics are modeled after the post-ICU clinics or are expanded versions of them.

The ICU Recovery Center at Vanderbilt University Medical Center, Nashville, Tenn., for instance, which opened in 2012, is accepting post-COVID patients.

There are about a dozen post-ICU clinics nationally, some of which are also now working with COVID patients, said James Jackson, director of long-term outcomes at the Vanderbilt center. In addition, he’s heard of at least another dozen post-COVID centers in development.

The centers generally do an initial assessment a few weeks after a patient is diagnosed or discharged from the hospital, often by video call. Check-in and repeat visits are scheduled every month or so after that.

“In an ideal world, with these post-COVID clinics, you can identify the patients and get them into rehab,” he said. “Even if the primary thing these clinics did was to say to patients: ‘This is real, it is not all in your head,’ that impact would be important.”
 

A question of feasibility

Financing is the largest obstacle, program proponents said. Many hospitals lost substantial revenue to canceled elective procedures during stay-at-home periods.

“So, it’s not a great time to be pitching a new activity that requires a start-up subsidy,” said Glenn Melnick, PhD, a professor of health economics at the University of Southern California.

At UCSF, a select group of faculty members staff the post-COVID clinics and some mental health professionals volunteer their time, said Dr. Santhosh.

Dr. Chen said he was able to recruit team members and support staff from the ranks of those whose elective patient caseload had dropped.

Dr. Jackson said unfortunately there’s not been enough research into the cost-and-clinical effectiveness of post-ICU centers.

“In the early days, there may have been questions about how much value does this add,” he noted. “Now, the question is not so much is it a good idea, but is it feasible?”

Right now, the post-COVID centers are foremost a research effort, said Len Nichols, an economist and nonresident fellow at the Urban Institute. “If these guys get good at treating long-term symptoms, that’s good for all of us. There’s not enough patients to make it a business model yet, but if they become the place to go when you get it, it could become a business model for some of the elite institutions.”

Kaiser Health News is a nonprofit news service covering health issues. It is an editorially independent program of KFF (Kaiser Family Foundation), which is not affiliated with Kaiser Permanente.

A novel algorithm for selecting patients who require treatment for obstructive sleep apnea (OSA) before undergoing bariatric surgery proved safe in a prospective cohort study of 1,103 patients.

Screening for OSA is recommended before bariatric surgery. OSA has been associated in several meta-analyses with increased risk for postoperative complications – not limited to bariatric surgery – and some studies have suggested that this increased risk may be limited to severe OSA, said Frédéric Series, MD, of Université Laval, Quebec City, at the virtual annual meeting of the Associated Sleep Societies.

The preoperative screening algorithm, which utilizes the results of nocturnal home oximetry and morning capillary gas measurements, effectively stratified patients for the risk of postoperative adverse events and “safely selected patients who don’t need [continuous positive airway pressure] before bariatric surgery,” he said. “The risk of postoperative adverse events following bariatric surgery was not increased in untreated OSA patients with low or moderate risk of severe OSA and hypoventilation.”

The study also demonstrated, he said, that patients with severe OSA with or without hypoventilation, even when correctly treated, remain at higher risk for complications.

The algorithm utilizes an oxygen desaturation index (ODI) corresponding to 3% drops in SaO₂ and the percent of the total recording time with an SaO₂ below 90%, as well as capillary gas measurements (PCO₂). Treatment was initiated for those with severe OSA (ODI ≥ 25/hr, < 10% of recording time with a SaO₂ below 90%) or OSA with hypoventilation (PCO₂ ≥ 45).

“When the ODI was less than 25 per hour, and when the total recording time spent below 90% SaO₂ was less than 10%, with PCO₂ < 45 mmHg, we expected no need for CPAP treatment,” Dr. Series said. For analysis, the investigators considered part of the untreated group – those with an ODI < 10/hr (no or mild OSA) – as a control group.

Treated patients underwent CPAP/BiPAP for a mean duration of 1.5 months. Good treatment compliance was mandatory for surgery, and treatment was continued immediately after extubation, in the recovery room, in nearly all patients, Dr. Series reported.

The analysis covered 1,103 patients: 447 controls (40.8%), 358 untreated (32.7%), 289 treated for OSA (26.4%) and 9 (0.8%) treated for OSA + hypoventilation. Patients with OSA, particularly those with severe OSA and those with hypoventilation, were older and heavier and significantly more likely to have hypertension and diabetes than controls.

There were no differences between the four groups in 10-day reoperation or 30-day readmission occurrence, and postoperative complications were “particularly infrequent in the control and OSA-untreated groups, with no differences between these two groups,” Dr. Series said.

Cardiac arrhythmia (mainly atrial fibrillation) occurred more frequently in the OSA-treated group (2.4%) and the OSA/hypoventilation patients (11%) than in the other groups (0.5%-0.6%).

Respiratory failure occurred in about one-third of patients with hypoventilation, and admission to the ICU was “dramatically higher” in patients with hypoventilation (67%), because of respiratory failure, arrhythmia, or other unstable medical conditions, Dr. Series said.

There were no differences between the groups in the duration of surgery or the amount of anesthetic used, but the length of stay in the recovery room was significantly longer in the OSA-treated and hypoventilation groups. The length of hospital stay was also longer in these groups. Sleeve gastrectomy was the most frequent bariatric surgical procedure across all groups, including 100% of patients with hypoventilation, he noted.

Asked to comment on the study, Octavian C. Ioachimescu, MD, PhD, of Emory University in Atlanta and the Atlanta Veterans Affairs Medical Center in Decatur, said the algorithm “clearly deserves further validation in other clinical-based cohorts and longer-term outcome assessment.”

Dr. Series reported that he has no relevant disclosures. Dr. Ioachimescu also said he has no relevant disclosures.
 

A novel algorithm for selecting patients who require treatment for obstructive sleep apnea (OSA) before undergoing bariatric surgery proved safe in a prospective cohort study of 1,103 patients.

Screening for OSA is recommended before bariatric surgery. OSA has been associated in several meta-analyses with increased risk for postoperative complications – not limited to bariatric surgery – and some studies have suggested that this increased risk may be limited to severe OSA, said Frédéric Series, MD, of Université Laval, Quebec City, at the virtual annual meeting of the Associated Sleep Societies.

The preoperative screening algorithm, which utilizes the results of nocturnal home oximetry and morning capillary gas measurements, effectively stratified patients for the risk of postoperative adverse events and “safely selected patients who don’t need [continuous positive airway pressure] before bariatric surgery,” he said. “The risk of postoperative adverse events following bariatric surgery was not increased in untreated OSA patients with low or moderate risk of severe OSA and hypoventilation.”

The study also demonstrated, he said, that patients with severe OSA with or without hypoventilation, even when correctly treated, remain at higher risk for complications.

The algorithm utilizes an oxygen desaturation index (ODI) corresponding to 3% drops in SaO₂ and the percent of the total recording time with an SaO₂ below 90%, as well as capillary gas measurements (PCO₂). Treatment was initiated for those with severe OSA (ODI ≥ 25/hr, < 10% of recording time with a SaO₂ below 90%) or OSA with hypoventilation (PCO₂ ≥ 45).

“When the ODI was less than 25 per hour, and when the total recording time spent below 90% SaO₂ was less than 10%, with PCO₂ < 45 mmHg, we expected no need for CPAP treatment,” Dr. Series said. For analysis, the investigators considered part of the untreated group – those with an ODI < 10/hr (no or mild OSA) – as a control group.

Treated patients underwent CPAP/BiPAP for a mean duration of 1.5 months. Good treatment compliance was mandatory for surgery, and treatment was continued immediately after extubation, in the recovery room, in nearly all patients, Dr. Series reported.

The analysis covered 1,103 patients: 447 controls (40.8%), 358 untreated (32.7%), 289 treated for OSA (26.4%) and 9 (0.8%) treated for OSA + hypoventilation. Patients with OSA, particularly those with severe OSA and those with hypoventilation, were older and heavier and significantly more likely to have hypertension and diabetes than controls.

There were no differences between the four groups in 10-day reoperation or 30-day readmission occurrence, and postoperative complications were “particularly infrequent in the control and OSA-untreated groups, with no differences between these two groups,” Dr. Series said.

Cardiac arrhythmia (mainly atrial fibrillation) occurred more frequently in the OSA-treated group (2.4%) and the OSA/hypoventilation patients (11%) than in the other groups (0.5%-0.6%).

Respiratory failure occurred in about one-third of patients with hypoventilation, and admission to the ICU was “dramatically higher” in patients with hypoventilation (67%), because of respiratory failure, arrhythmia, or other unstable medical conditions, Dr. Series said.

There were no differences between the groups in the duration of surgery or the amount of anesthetic used, but the length of stay in the recovery room was significantly longer in the OSA-treated and hypoventilation groups. The length of hospital stay was also longer in these groups. Sleeve gastrectomy was the most frequent bariatric surgical procedure across all groups, including 100% of patients with hypoventilation, he noted.

Asked to comment on the study, Octavian C. Ioachimescu, MD, PhD, of Emory University in Atlanta and the Atlanta Veterans Affairs Medical Center in Decatur, said the algorithm “clearly deserves further validation in other clinical-based cohorts and longer-term outcome assessment.”

Dr. Series reported that he has no relevant disclosures. Dr. Ioachimescu also said he has no relevant disclosures.
 

A novel algorithm for selecting patients who require treatment for obstructive sleep apnea (OSA) before undergoing bariatric surgery proved safe in a prospective cohort study of 1,103 patients.

Screening for OSA is recommended before bariatric surgery. OSA has been associated in several meta-analyses with increased risk for postoperative complications – not limited to bariatric surgery – and some studies have suggested that this increased risk may be limited to severe OSA, said Frédéric Series, MD, of Université Laval, Quebec City, at the virtual annual meeting of the Associated Sleep Societies.

The preoperative screening algorithm, which utilizes the results of nocturnal home oximetry and morning capillary gas measurements, effectively stratified patients for the risk of postoperative adverse events and “safely selected patients who don’t need [continuous positive airway pressure] before bariatric surgery,” he said. “The risk of postoperative adverse events following bariatric surgery was not increased in untreated OSA patients with low or moderate risk of severe OSA and hypoventilation.”

The study also demonstrated, he said, that patients with severe OSA with or without hypoventilation, even when correctly treated, remain at higher risk for complications.

The algorithm utilizes an oxygen desaturation index (ODI) corresponding to 3% drops in SaO₂ and the percent of the total recording time with an SaO₂ below 90%, as well as capillary gas measurements (PCO₂). Treatment was initiated for those with severe OSA (ODI ≥ 25/hr, < 10% of recording time with a SaO₂ below 90%) or OSA with hypoventilation (PCO₂ ≥ 45).

“When the ODI was less than 25 per hour, and when the total recording time spent below 90% SaO₂ was less than 10%, with PCO₂ < 45 mmHg, we expected no need for CPAP treatment,” Dr. Series said. For analysis, the investigators considered part of the untreated group – those with an ODI < 10/hr (no or mild OSA) – as a control group.

Treated patients underwent CPAP/BiPAP for a mean duration of 1.5 months. Good treatment compliance was mandatory for surgery, and treatment was continued immediately after extubation, in the recovery room, in nearly all patients, Dr. Series reported.

The analysis covered 1,103 patients: 447 controls (40.8%), 358 untreated (32.7%), 289 treated for OSA (26.4%) and 9 (0.8%) treated for OSA + hypoventilation. Patients with OSA, particularly those with severe OSA and those with hypoventilation, were older and heavier and significantly more likely to have hypertension and diabetes than controls.

There were no differences between the four groups in 10-day reoperation or 30-day readmission occurrence, and postoperative complications were “particularly infrequent in the control and OSA-untreated groups, with no differences between these two groups,” Dr. Series said.

Cardiac arrhythmia (mainly atrial fibrillation) occurred more frequently in the OSA-treated group (2.4%) and the OSA/hypoventilation patients (11%) than in the other groups (0.5%-0.6%).

Respiratory failure occurred in about one-third of patients with hypoventilation, and admission to the ICU was “dramatically higher” in patients with hypoventilation (67%), because of respiratory failure, arrhythmia, or other unstable medical conditions, Dr. Series said.

There were no differences between the groups in the duration of surgery or the amount of anesthetic used, but the length of stay in the recovery room was significantly longer in the OSA-treated and hypoventilation groups. The length of hospital stay was also longer in these groups. Sleeve gastrectomy was the most frequent bariatric surgical procedure across all groups, including 100% of patients with hypoventilation, he noted.

Asked to comment on the study, Octavian C. Ioachimescu, MD, PhD, of Emory University in Atlanta and the Atlanta Veterans Affairs Medical Center in Decatur, said the algorithm “clearly deserves further validation in other clinical-based cohorts and longer-term outcome assessment.”

Dr. Series reported that he has no relevant disclosures. Dr. Ioachimescu also said he has no relevant disclosures.