Neurology Reviews

Measuring serum levels of neurofilament light chain (NfL) is an effective way of detecting disease activity and the need to optimize treatment in patients with multiple sclerosis (MS), independent of relapse and MRI activity, a new study has shown. 

The study found that current serum NfL levels predicted relapses, disability worsening, and MRI activity in the following year independent of standard metrics for treatment monitoring, such as relapse rate, disability worsening, and MRI findings. The biomarker also detected subclinical disease activity in patients with no evidence of disease activity (NEDA3), as measured by absence of previous relapses, worsening score on the Expanded Disability Status Scale (EDSS), or brain lesion formation on MRI. 

“Our data in this well-characterized large real-world cohort supports the value of serum NfL levels for treatment monitoring in MS clinical practice,” lead author Özgür Yaldizli, MD, concluded.

Dr. Yaldizli, who is a consultant neurologist at University Hospital Basel (Switzerland), presented the findings at the Joint European Committee for Treatment and Research in Multiple Sclerosis–Americas Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS-ACTRIMS) 2020, this year known as MSVirtual2020.

“This is the first study to compare NfL simultaneously with other markers of disease progression, such as MRI lesions and relapse rate in treated patients. We show that NfL gives a unique signal that is not captured by other markers,” Dr. Yaldizli said.

“This is likely the largest study of NfL in MS to date, with more than 7,000 samples from well-characterized MS patients followed longitudinally for more than 5 years of sampling and including high quality data on MRI and clinical examinations. It is the first time all these factors have been combined so that we can see how NfL compares with other markers of disease progression in predicting clinical events and monitoring treatment efficacy,” said senior author Jens Kuhle, MD, PhD, also from University Hospital Basel. 
 

Large normative database for reference

The researchers also reported a large normative database of NfL values with data from more than 8,000 healthy controls. “This is the largest normative database to date, that gives us reliable reference values for NfL across a range of ages and comorbidities,” Dr. Kuhle noted.

In his presentation, Dr. Yaldizli explained that NfL is a neuronal cytoskeletal protein released into the cerebrospinal fluid and blood following neuroaxonal injury. Although numerous studies have shown that serum NfL is associated with clinical and MRI disease activity and treatment response, it is not clear whether serum NfL under established disease-modifying therapy (DMT) can identify patients with suboptimal treatment response, compared with standard clinical and MRI activity measures.

This study addressed that question in the large real-world Swiss MS cohort.

The study involved 1,366 patients (88.8% with relapsing remitting MS [RRMS], 5.4% with secondary progressive MS, and 5.8% with primary progressive MS) receiving DMT for at least 3 months from seven MS centers. The median disease duration was 7.2 years. Serum NfL was measured every 6 or 12 months with NF-Light assay on the latest-generation HDX platform (blinded for clinical and MRI data). The median follow-up was 4.9 years. There was an average of five samples per patient, with a total of 7462 samples.

Results showed that NfL levels were higher in older patients (14.5% per 10 years), those with secondary progressive MS (12.4% vs. RRMS), those with primary progressive MS (14.4% vs. RRMS), and in those who had a relapse in the last 4 months (53.4%).

NfL levels were 13.4% lower in patients receiving oral DMT (vs. untreated patients) and 17.7% in patients receiving monoclonal antibodies (vs. untreated patients).

In the large cohort of healthy controls, NfL levels also increased with age, but levels in patients with MS were higher than in controls across the whole age spectrum.

To obtain a measure of deviation from normal, the authors converted NfL levels to z score, which express how much (in terms of number of standard deviations) a measurement differs from mean values found in healthy controls of the same age. Effects were more pronounced with use of z score derived from the normative database than with use of absolute NfL levels even after adjustment for age.

In the univariate analysis, serum NfL z score predicted relapse or EDSS worsening in the following year: The higher the z score, the higher the risk for relapse or EDSS worsening. Patients with an NfL z score greater than 1 had a 41% higher risk for relapse or EDSS worsening in the following year, compared with those whose z score was less than 1 (odds ratio, 1.41).

Patients with an NfL z score exceeding 1.5 had an 80% higher risk for relapse or EDSS worsening in the following year than did those whose score was below 1.5 (OR, 1.8).

Patients with an NfL z score greater than 2 had a 2.3 times higher risk for relapse or EDSS worsening in the following year versus those with a score below 2. (P < 0.001 for all comparisons.)

A screen for nervous system conditions?

Dr, Kuhle reported that NfL is being used on an individual basis in clinical practice at present – at certain MS centers. “One of the problems is not having reliable reference values, so this database of normative values will be very helpful in developing those,” he said. “We see an increase in NfL with age in healthy controls. In order to know what pathological levels are, we need to know what normal levels are in controls throughout the spectrum of ages and other comorbidities, which also play a role. If we normalize these, then we can work out the MS signal in a more efficient way.”

Dr. Kuhle believes that, in the future, NfL may be used to screen for nervous system disease. “NfL is a measure of neuronal health independent of MS. If we have increased levels, we should be worried.”

There is a “high level of energy in this field,” he added. “In future, it could be like having a cholesterol test at present – picking up that something is not right and indicating the need for more tests.”

Dr. Yaldizli suggested that NfL monitoring could also help to individualize and optimize use of MS treatments. “There is a huge unmet need in MS. While we have a plethora of treatment options, we are struggling to individualize and monitor treatments. If NfL levels increase, this is likely a strong indication to change treatment even if there are no other overt symptoms.”

Commenting on the current study, ACTRIMS president, Jeffrey Cohen, MD, Mellen Center for Multiple Sclerosis Treatment and Research at the Cleveland Clinic, called it “an important study.” 

“NfL clearly can detect disease activity and distinguish efficacy of DMT in groups of patients,” Dr. Cohen said.  

“This study shows that NfL can be used to monitor DMT efficacy in individual patients and can detect suboptimal treatment response in patients with NEDA (i.e., who appear stable by the measures we typically employ in practice),” he added.

Dr. Yaldizli sits on advisory boards for Sanofi Genzyme, Novartis, Biogen, and Novartis. Dr. Kuhle reported no relevant disclosures.

This article first appeared on Medscape.com.

Measuring serum levels of neurofilament light chain (NfL) is an effective way of detecting disease activity and the need to optimize treatment in patients with multiple sclerosis (MS), independent of relapse and MRI activity, a new study has shown. 

The study found that current serum NfL levels predicted relapses, disability worsening, and MRI activity in the following year independent of standard metrics for treatment monitoring, such as relapse rate, disability worsening, and MRI findings. The biomarker also detected subclinical disease activity in patients with no evidence of disease activity (NEDA3), as measured by absence of previous relapses, worsening score on the Expanded Disability Status Scale (EDSS), or brain lesion formation on MRI. 

“Our data in this well-characterized large real-world cohort supports the value of serum NfL levels for treatment monitoring in MS clinical practice,” lead author Özgür Yaldizli, MD, concluded.

Dr. Yaldizli, who is a consultant neurologist at University Hospital Basel (Switzerland), presented the findings at the Joint European Committee for Treatment and Research in Multiple Sclerosis–Americas Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS-ACTRIMS) 2020, this year known as MSVirtual2020.

“This is the first study to compare NfL simultaneously with other markers of disease progression, such as MRI lesions and relapse rate in treated patients. We show that NfL gives a unique signal that is not captured by other markers,” Dr. Yaldizli said.

“This is likely the largest study of NfL in MS to date, with more than 7,000 samples from well-characterized MS patients followed longitudinally for more than 5 years of sampling and including high quality data on MRI and clinical examinations. It is the first time all these factors have been combined so that we can see how NfL compares with other markers of disease progression in predicting clinical events and monitoring treatment efficacy,” said senior author Jens Kuhle, MD, PhD, also from University Hospital Basel. 
 

Large normative database for reference

The researchers also reported a large normative database of NfL values with data from more than 8,000 healthy controls. “This is the largest normative database to date, that gives us reliable reference values for NfL across a range of ages and comorbidities,” Dr. Kuhle noted.

In his presentation, Dr. Yaldizli explained that NfL is a neuronal cytoskeletal protein released into the cerebrospinal fluid and blood following neuroaxonal injury. Although numerous studies have shown that serum NfL is associated with clinical and MRI disease activity and treatment response, it is not clear whether serum NfL under established disease-modifying therapy (DMT) can identify patients with suboptimal treatment response, compared with standard clinical and MRI activity measures.

This study addressed that question in the large real-world Swiss MS cohort.

The study involved 1,366 patients (88.8% with relapsing remitting MS [RRMS], 5.4% with secondary progressive MS, and 5.8% with primary progressive MS) receiving DMT for at least 3 months from seven MS centers. The median disease duration was 7.2 years. Serum NfL was measured every 6 or 12 months with NF-Light assay on the latest-generation HDX platform (blinded for clinical and MRI data). The median follow-up was 4.9 years. There was an average of five samples per patient, with a total of 7462 samples.

Results showed that NfL levels were higher in older patients (14.5% per 10 years), those with secondary progressive MS (12.4% vs. RRMS), those with primary progressive MS (14.4% vs. RRMS), and in those who had a relapse in the last 4 months (53.4%).

NfL levels were 13.4% lower in patients receiving oral DMT (vs. untreated patients) and 17.7% in patients receiving monoclonal antibodies (vs. untreated patients).

In the large cohort of healthy controls, NfL levels also increased with age, but levels in patients with MS were higher than in controls across the whole age spectrum.

To obtain a measure of deviation from normal, the authors converted NfL levels to z score, which express how much (in terms of number of standard deviations) a measurement differs from mean values found in healthy controls of the same age. Effects were more pronounced with use of z score derived from the normative database than with use of absolute NfL levels even after adjustment for age.

In the univariate analysis, serum NfL z score predicted relapse or EDSS worsening in the following year: The higher the z score, the higher the risk for relapse or EDSS worsening. Patients with an NfL z score greater than 1 had a 41% higher risk for relapse or EDSS worsening in the following year, compared with those whose z score was less than 1 (odds ratio, 1.41).

Patients with an NfL z score exceeding 1.5 had an 80% higher risk for relapse or EDSS worsening in the following year than did those whose score was below 1.5 (OR, 1.8).

Patients with an NfL z score greater than 2 had a 2.3 times higher risk for relapse or EDSS worsening in the following year versus those with a score below 2. (P < 0.001 for all comparisons.)

A screen for nervous system conditions?

Dr, Kuhle reported that NfL is being used on an individual basis in clinical practice at present – at certain MS centers. “One of the problems is not having reliable reference values, so this database of normative values will be very helpful in developing those,” he said. “We see an increase in NfL with age in healthy controls. In order to know what pathological levels are, we need to know what normal levels are in controls throughout the spectrum of ages and other comorbidities, which also play a role. If we normalize these, then we can work out the MS signal in a more efficient way.”

Dr. Kuhle believes that, in the future, NfL may be used to screen for nervous system disease. “NfL is a measure of neuronal health independent of MS. If we have increased levels, we should be worried.”

There is a “high level of energy in this field,” he added. “In future, it could be like having a cholesterol test at present – picking up that something is not right and indicating the need for more tests.”

Dr. Yaldizli suggested that NfL monitoring could also help to individualize and optimize use of MS treatments. “There is a huge unmet need in MS. While we have a plethora of treatment options, we are struggling to individualize and monitor treatments. If NfL levels increase, this is likely a strong indication to change treatment even if there are no other overt symptoms.”

Commenting on the current study, ACTRIMS president, Jeffrey Cohen, MD, Mellen Center for Multiple Sclerosis Treatment and Research at the Cleveland Clinic, called it “an important study.” 

“NfL clearly can detect disease activity and distinguish efficacy of DMT in groups of patients,” Dr. Cohen said.  

“This study shows that NfL can be used to monitor DMT efficacy in individual patients and can detect suboptimal treatment response in patients with NEDA (i.e., who appear stable by the measures we typically employ in practice),” he added.

Dr. Yaldizli sits on advisory boards for Sanofi Genzyme, Novartis, Biogen, and Novartis. Dr. Kuhle reported no relevant disclosures.

This article first appeared on Medscape.com.

Measuring serum levels of neurofilament light chain (NfL) is an effective way of detecting disease activity and the need to optimize treatment in patients with multiple sclerosis (MS), independent of relapse and MRI activity, a new study has shown. 

The study found that current serum NfL levels predicted relapses, disability worsening, and MRI activity in the following year independent of standard metrics for treatment monitoring, such as relapse rate, disability worsening, and MRI findings. The biomarker also detected subclinical disease activity in patients with no evidence of disease activity (NEDA3), as measured by absence of previous relapses, worsening score on the Expanded Disability Status Scale (EDSS), or brain lesion formation on MRI. 

“Our data in this well-characterized large real-world cohort supports the value of serum NfL levels for treatment monitoring in MS clinical practice,” lead author Özgür Yaldizli, MD, concluded.

Dr. Yaldizli, who is a consultant neurologist at University Hospital Basel (Switzerland), presented the findings at the Joint European Committee for Treatment and Research in Multiple Sclerosis–Americas Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS-ACTRIMS) 2020, this year known as MSVirtual2020.

“This is the first study to compare NfL simultaneously with other markers of disease progression, such as MRI lesions and relapse rate in treated patients. We show that NfL gives a unique signal that is not captured by other markers,” Dr. Yaldizli said.

“This is likely the largest study of NfL in MS to date, with more than 7,000 samples from well-characterized MS patients followed longitudinally for more than 5 years of sampling and including high quality data on MRI and clinical examinations. It is the first time all these factors have been combined so that we can see how NfL compares with other markers of disease progression in predicting clinical events and monitoring treatment efficacy,” said senior author Jens Kuhle, MD, PhD, also from University Hospital Basel. 
 

Large normative database for reference

The researchers also reported a large normative database of NfL values with data from more than 8,000 healthy controls. “This is the largest normative database to date, that gives us reliable reference values for NfL across a range of ages and comorbidities,” Dr. Kuhle noted.

In his presentation, Dr. Yaldizli explained that NfL is a neuronal cytoskeletal protein released into the cerebrospinal fluid and blood following neuroaxonal injury. Although numerous studies have shown that serum NfL is associated with clinical and MRI disease activity and treatment response, it is not clear whether serum NfL under established disease-modifying therapy (DMT) can identify patients with suboptimal treatment response, compared with standard clinical and MRI activity measures.

This study addressed that question in the large real-world Swiss MS cohort.

The study involved 1,366 patients (88.8% with relapsing remitting MS [RRMS], 5.4% with secondary progressive MS, and 5.8% with primary progressive MS) receiving DMT for at least 3 months from seven MS centers. The median disease duration was 7.2 years. Serum NfL was measured every 6 or 12 months with NF-Light assay on the latest-generation HDX platform (blinded for clinical and MRI data). The median follow-up was 4.9 years. There was an average of five samples per patient, with a total of 7462 samples.

Results showed that NfL levels were higher in older patients (14.5% per 10 years), those with secondary progressive MS (12.4% vs. RRMS), those with primary progressive MS (14.4% vs. RRMS), and in those who had a relapse in the last 4 months (53.4%).

NfL levels were 13.4% lower in patients receiving oral DMT (vs. untreated patients) and 17.7% in patients receiving monoclonal antibodies (vs. untreated patients).

In the large cohort of healthy controls, NfL levels also increased with age, but levels in patients with MS were higher than in controls across the whole age spectrum.

To obtain a measure of deviation from normal, the authors converted NfL levels to z score, which express how much (in terms of number of standard deviations) a measurement differs from mean values found in healthy controls of the same age. Effects were more pronounced with use of z score derived from the normative database than with use of absolute NfL levels even after adjustment for age.

In the univariate analysis, serum NfL z score predicted relapse or EDSS worsening in the following year: The higher the z score, the higher the risk for relapse or EDSS worsening. Patients with an NfL z score greater than 1 had a 41% higher risk for relapse or EDSS worsening in the following year, compared with those whose z score was less than 1 (odds ratio, 1.41).

Patients with an NfL z score exceeding 1.5 had an 80% higher risk for relapse or EDSS worsening in the following year than did those whose score was below 1.5 (OR, 1.8).

Patients with an NfL z score greater than 2 had a 2.3 times higher risk for relapse or EDSS worsening in the following year versus those with a score below 2. (P < 0.001 for all comparisons.)

A screen for nervous system conditions?

Dr, Kuhle reported that NfL is being used on an individual basis in clinical practice at present – at certain MS centers. “One of the problems is not having reliable reference values, so this database of normative values will be very helpful in developing those,” he said. “We see an increase in NfL with age in healthy controls. In order to know what pathological levels are, we need to know what normal levels are in controls throughout the spectrum of ages and other comorbidities, which also play a role. If we normalize these, then we can work out the MS signal in a more efficient way.”

Dr. Kuhle believes that, in the future, NfL may be used to screen for nervous system disease. “NfL is a measure of neuronal health independent of MS. If we have increased levels, we should be worried.”

There is a “high level of energy in this field,” he added. “In future, it could be like having a cholesterol test at present – picking up that something is not right and indicating the need for more tests.”

Dr. Yaldizli suggested that NfL monitoring could also help to individualize and optimize use of MS treatments. “There is a huge unmet need in MS. While we have a plethora of treatment options, we are struggling to individualize and monitor treatments. If NfL levels increase, this is likely a strong indication to change treatment even if there are no other overt symptoms.”

Commenting on the current study, ACTRIMS president, Jeffrey Cohen, MD, Mellen Center for Multiple Sclerosis Treatment and Research at the Cleveland Clinic, called it “an important study.” 

“NfL clearly can detect disease activity and distinguish efficacy of DMT in groups of patients,” Dr. Cohen said.  

“This study shows that NfL can be used to monitor DMT efficacy in individual patients and can detect suboptimal treatment response in patients with NEDA (i.e., who appear stable by the measures we typically employ in practice),” he added.

Dr. Yaldizli sits on advisory boards for Sanofi Genzyme, Novartis, Biogen, and Novartis. Dr. Kuhle reported no relevant disclosures.

This article first appeared on Medscape.com.

A smartphone app that combines passively collected physiologic data from wearable devices, such as fitness trackers, and self-reported symptoms can discriminate between COVID-19–positive and –negative individuals among those who report symptoms, new data suggest.

LDProd/Getty Images

After analyzing data from more than 30,000 participants, researchers from the Digital Engagement and Tracking for Early Control and Treatment (DETECT) study concluded that adding individual changes in sensor data improves models based on symptoms alone for differentiating symptomatic persons who are COVID-19 positive and symptomatic persons who are COVID-19 negative.

The combination can potentially identify infection clusters before wider community spread occurs, Giorgio Quer, PhD, and colleagues report in an article published online Oct. 29 in Nature Medicine. DETECT investigators note that marrying participant-reported symptoms with personal sensor data, such as deviation from normal sleep duration and resting heart rate, resulted in an area under the curve (AUC) of 0.80 (interquartile range [IQR], 0.73-0.86) for differentiating between symptomatic individuals who were positive and those who were negative for COVID-19.

“By better characterizing each individual’s unique baseline, you can then identify changes that may indicate that someone has a viral illness,” said Dr. Quer, director of artificial intelligence at Scripps Research Translational Institute in La Jolla, Calif. “In previous research, we found that the proportion of individuals with elevated resting heart rate and sleep duration compared with their normal could significantly improve real-time detection of influenza-like illness rates at the state level,” he said in an interview.

Thus, continuous passively captured data may be a useful adjunct to bricks-and-mortar site testing, which is generally a one-off or infrequent sampling assay and is not always easily accessible, he added. Furthermore, traditional screening with temperature and symptom reporting is inadequate. An elevation in temperature is not as common as frequently believed for people who test positive for COVID-19, Dr. Quer continued. “Early identification via sensor variables of those who are presymptomatic or even asymptomatic would be especially valuable, as people may potentially be infectious during this period, and early detection is the ultimate goal,” Dr. Quer said.

According to his group, adding these physiologic changes from baseline values significantly outperformed detection (P < .01) using a British model described in an earlier study by by Cristina Menni, PhD, and associates. That method, in which symptoms were considered alone, yielded an AUC of 0.71 (IQR, 0.63-0.79).

According to Dr. Quer, one in five Americans currently wear an electronic device. “If we could enroll even a small percentage of these individuals, we’d be able to potentially identify clusters before they have the opportunity to spread,” he said.
 

DETECT study details

During the period March 15 to June 7, 2020, the study enrolled 30,529 participants from all 50 states. They ranged in age from younger than 35 years (23.1%) to older than 65 years (12.8%); the majority (63.5%) were aged 35-65 years, and 62% were women. Sensor devices in use by the cohort included Fitbit activity trackers (78.4%) and Apple HealthKit (31.2%).

Participants downloaded an app called MyDataHelps, which collects smartwatch and activity tracker information, including self-reported symptoms and diagnostic testing results. The app also monitors changes from baseline in resting heart rate, sleep duration, and physical activity, as measured by steps.

Overall, 3,811 participants reported having at least one symptom of some kind (e.g., fatigue, cough, dyspnea, loss of taste or smell). Of these, 54 reported testing positive for COVID-19, and 279 reported testing negative.

Sleep and activity were significantly different for the positive and negative groups, with an AUC of 0.68 (IQR, 0.57-0.79) for the sleep metric and 0.69 (IQR, 0.61-0.77) for the activity metric, suggesting that these parameters were more affected in COVID-19–positive participants.

When the investigators combined resting heart rate, sleep, and activity into a single metric, predictive performance improved to an AUC of 0.72 (IQR, 0.64-0.80).

The next step, Dr. Quer said, is to include an alert to notify users of possible infection.
 

Alerting users to possible COVID-19 infection

In a similar study, an alert feature was already incorporated. The study, led by Michael P. Snyder, PhD, director of the Center for Genomics and Personalized Medicine at Stanford (Calif.) University, will soon be published online in Nature Biomedical Engineering. In that study, presymptomatic detection of COVID-19 was achieved in more than 80% of participants using resting heart rate.

“The median is 4 days prior to symptom formation,” Dr. Snyder said in an interview. “We have an alarm system to notify people when their heart rate is elevated. So a positive signal from a smartwatch can be used to follow up by polymerase chain reaction [testing].”

Dr. Snyder said these approaches offer a roadmap to containing widespread infections. “Public health authorities need to be open to these technologies and begin incorporating them into their tracking,” he said. “Right now, people do temperature checks, which are of limited value. Resting heart rate is much better information.”

Although the DETECT researchers have not yet received feedback on their results, they believe public health authorities could recommend the use of such apps. “These are devices that people routinely wear for tracking their fitness and sleep, so it would be relatively easy to use the data for viral illness tracking,” said co–lead author Jennifer Radin, PhD, an epidemiologist at Scripps. “Testing resources are still limited and don’t allow for routine serial testing of individuals who may be asymptomatic or presymptomatic. Wearables can offer a different way to routinely monitor and screen people for changes in their data that may indicate COVID-19.”

The marshaling of data through consumer digital platforms to fight the coronavirus is gaining ground. New York State and New Jersey are already embracing smartphone apps to alert individuals to possible exposure to the virus.

More than 710,000 New Yorkers have downloaded the COVID NY Alert app, launched in October to help protect individuals and communities from COVID-19 by sending alerts without compromising privacy or personal information. “Upon receiving a notification about a potential exposure, users are then able to self-quarantine, get tested, and reduce the potential exposure risk to family, friends, coworkers, and others,” Jonah Bruno, a spokesperson for the New York State Department of Health, said in an interview.

And recently the Mayo Clinic and Safe Health Systems launched a platform to store COVID-19 testing and vaccination data.

Both the Scripps and Stanford platforms are part of a global technologic response to the COVID-19 pandemic. Prospective studies, led by device manufacturers and academic institutions, allow individuals to voluntarily share sensor and clinical data to address the crisis. Similar approaches have been used to track COVID-19 in large populations in Germany via the Corona Data Donation app.

The study by Dr. Quer and colleagues was funded by a grant from the National Center for Advancing Translational Sciences at the National Institutes of Health. One coauthor reported grants from Janssen and personal fees from Otsuka and Livongo outside of the submitted work. The other authors have disclosed no relevant financial relationships. Dr. Snyder has ties to Personalis, Qbio, January, SensOmics, Protos, Mirvie, and Oralome.
 

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

A smartphone app that combines passively collected physiologic data from wearable devices, such as fitness trackers, and self-reported symptoms can discriminate between COVID-19–positive and –negative individuals among those who report symptoms, new data suggest.

LDProd/Getty Images

After analyzing data from more than 30,000 participants, researchers from the Digital Engagement and Tracking for Early Control and Treatment (DETECT) study concluded that adding individual changes in sensor data improves models based on symptoms alone for differentiating symptomatic persons who are COVID-19 positive and symptomatic persons who are COVID-19 negative.

The combination can potentially identify infection clusters before wider community spread occurs, Giorgio Quer, PhD, and colleagues report in an article published online Oct. 29 in Nature Medicine. DETECT investigators note that marrying participant-reported symptoms with personal sensor data, such as deviation from normal sleep duration and resting heart rate, resulted in an area under the curve (AUC) of 0.80 (interquartile range [IQR], 0.73-0.86) for differentiating between symptomatic individuals who were positive and those who were negative for COVID-19.

“By better characterizing each individual’s unique baseline, you can then identify changes that may indicate that someone has a viral illness,” said Dr. Quer, director of artificial intelligence at Scripps Research Translational Institute in La Jolla, Calif. “In previous research, we found that the proportion of individuals with elevated resting heart rate and sleep duration compared with their normal could significantly improve real-time detection of influenza-like illness rates at the state level,” he said in an interview.

Thus, continuous passively captured data may be a useful adjunct to bricks-and-mortar site testing, which is generally a one-off or infrequent sampling assay and is not always easily accessible, he added. Furthermore, traditional screening with temperature and symptom reporting is inadequate. An elevation in temperature is not as common as frequently believed for people who test positive for COVID-19, Dr. Quer continued. “Early identification via sensor variables of those who are presymptomatic or even asymptomatic would be especially valuable, as people may potentially be infectious during this period, and early detection is the ultimate goal,” Dr. Quer said.

According to his group, adding these physiologic changes from baseline values significantly outperformed detection (P < .01) using a British model described in an earlier study by by Cristina Menni, PhD, and associates. That method, in which symptoms were considered alone, yielded an AUC of 0.71 (IQR, 0.63-0.79).

According to Dr. Quer, one in five Americans currently wear an electronic device. “If we could enroll even a small percentage of these individuals, we’d be able to potentially identify clusters before they have the opportunity to spread,” he said.
 

DETECT study details

During the period March 15 to June 7, 2020, the study enrolled 30,529 participants from all 50 states. They ranged in age from younger than 35 years (23.1%) to older than 65 years (12.8%); the majority (63.5%) were aged 35-65 years, and 62% were women. Sensor devices in use by the cohort included Fitbit activity trackers (78.4%) and Apple HealthKit (31.2%).

Participants downloaded an app called MyDataHelps, which collects smartwatch and activity tracker information, including self-reported symptoms and diagnostic testing results. The app also monitors changes from baseline in resting heart rate, sleep duration, and physical activity, as measured by steps.

Overall, 3,811 participants reported having at least one symptom of some kind (e.g., fatigue, cough, dyspnea, loss of taste or smell). Of these, 54 reported testing positive for COVID-19, and 279 reported testing negative.

Sleep and activity were significantly different for the positive and negative groups, with an AUC of 0.68 (IQR, 0.57-0.79) for the sleep metric and 0.69 (IQR, 0.61-0.77) for the activity metric, suggesting that these parameters were more affected in COVID-19–positive participants.

When the investigators combined resting heart rate, sleep, and activity into a single metric, predictive performance improved to an AUC of 0.72 (IQR, 0.64-0.80).

The next step, Dr. Quer said, is to include an alert to notify users of possible infection.
 

Alerting users to possible COVID-19 infection

In a similar study, an alert feature was already incorporated. The study, led by Michael P. Snyder, PhD, director of the Center for Genomics and Personalized Medicine at Stanford (Calif.) University, will soon be published online in Nature Biomedical Engineering. In that study, presymptomatic detection of COVID-19 was achieved in more than 80% of participants using resting heart rate.

“The median is 4 days prior to symptom formation,” Dr. Snyder said in an interview. “We have an alarm system to notify people when their heart rate is elevated. So a positive signal from a smartwatch can be used to follow up by polymerase chain reaction [testing].”

Dr. Snyder said these approaches offer a roadmap to containing widespread infections. “Public health authorities need to be open to these technologies and begin incorporating them into their tracking,” he said. “Right now, people do temperature checks, which are of limited value. Resting heart rate is much better information.”

Although the DETECT researchers have not yet received feedback on their results, they believe public health authorities could recommend the use of such apps. “These are devices that people routinely wear for tracking their fitness and sleep, so it would be relatively easy to use the data for viral illness tracking,” said co–lead author Jennifer Radin, PhD, an epidemiologist at Scripps. “Testing resources are still limited and don’t allow for routine serial testing of individuals who may be asymptomatic or presymptomatic. Wearables can offer a different way to routinely monitor and screen people for changes in their data that may indicate COVID-19.”

The marshaling of data through consumer digital platforms to fight the coronavirus is gaining ground. New York State and New Jersey are already embracing smartphone apps to alert individuals to possible exposure to the virus.

More than 710,000 New Yorkers have downloaded the COVID NY Alert app, launched in October to help protect individuals and communities from COVID-19 by sending alerts without compromising privacy or personal information. “Upon receiving a notification about a potential exposure, users are then able to self-quarantine, get tested, and reduce the potential exposure risk to family, friends, coworkers, and others,” Jonah Bruno, a spokesperson for the New York State Department of Health, said in an interview.

And recently the Mayo Clinic and Safe Health Systems launched a platform to store COVID-19 testing and vaccination data.

Both the Scripps and Stanford platforms are part of a global technologic response to the COVID-19 pandemic. Prospective studies, led by device manufacturers and academic institutions, allow individuals to voluntarily share sensor and clinical data to address the crisis. Similar approaches have been used to track COVID-19 in large populations in Germany via the Corona Data Donation app.

The study by Dr. Quer and colleagues was funded by a grant from the National Center for Advancing Translational Sciences at the National Institutes of Health. One coauthor reported grants from Janssen and personal fees from Otsuka and Livongo outside of the submitted work. The other authors have disclosed no relevant financial relationships. Dr. Snyder has ties to Personalis, Qbio, January, SensOmics, Protos, Mirvie, and Oralome.
 

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

A smartphone app that combines passively collected physiologic data from wearable devices, such as fitness trackers, and self-reported symptoms can discriminate between COVID-19–positive and –negative individuals among those who report symptoms, new data suggest.

LDProd/Getty Images

After analyzing data from more than 30,000 participants, researchers from the Digital Engagement and Tracking for Early Control and Treatment (DETECT) study concluded that adding individual changes in sensor data improves models based on symptoms alone for differentiating symptomatic persons who are COVID-19 positive and symptomatic persons who are COVID-19 negative.

The combination can potentially identify infection clusters before wider community spread occurs, Giorgio Quer, PhD, and colleagues report in an article published online Oct. 29 in Nature Medicine. DETECT investigators note that marrying participant-reported symptoms with personal sensor data, such as deviation from normal sleep duration and resting heart rate, resulted in an area under the curve (AUC) of 0.80 (interquartile range [IQR], 0.73-0.86) for differentiating between symptomatic individuals who were positive and those who were negative for COVID-19.

“By better characterizing each individual’s unique baseline, you can then identify changes that may indicate that someone has a viral illness,” said Dr. Quer, director of artificial intelligence at Scripps Research Translational Institute in La Jolla, Calif. “In previous research, we found that the proportion of individuals with elevated resting heart rate and sleep duration compared with their normal could significantly improve real-time detection of influenza-like illness rates at the state level,” he said in an interview.

Thus, continuous passively captured data may be a useful adjunct to bricks-and-mortar site testing, which is generally a one-off or infrequent sampling assay and is not always easily accessible, he added. Furthermore, traditional screening with temperature and symptom reporting is inadequate. An elevation in temperature is not as common as frequently believed for people who test positive for COVID-19, Dr. Quer continued. “Early identification via sensor variables of those who are presymptomatic or even asymptomatic would be especially valuable, as people may potentially be infectious during this period, and early detection is the ultimate goal,” Dr. Quer said.

According to his group, adding these physiologic changes from baseline values significantly outperformed detection (P < .01) using a British model described in an earlier study by by Cristina Menni, PhD, and associates. That method, in which symptoms were considered alone, yielded an AUC of 0.71 (IQR, 0.63-0.79).

According to Dr. Quer, one in five Americans currently wear an electronic device. “If we could enroll even a small percentage of these individuals, we’d be able to potentially identify clusters before they have the opportunity to spread,” he said.
 

DETECT study details

During the period March 15 to June 7, 2020, the study enrolled 30,529 participants from all 50 states. They ranged in age from younger than 35 years (23.1%) to older than 65 years (12.8%); the majority (63.5%) were aged 35-65 years, and 62% were women. Sensor devices in use by the cohort included Fitbit activity trackers (78.4%) and Apple HealthKit (31.2%).

Participants downloaded an app called MyDataHelps, which collects smartwatch and activity tracker information, including self-reported symptoms and diagnostic testing results. The app also monitors changes from baseline in resting heart rate, sleep duration, and physical activity, as measured by steps.

Overall, 3,811 participants reported having at least one symptom of some kind (e.g., fatigue, cough, dyspnea, loss of taste or smell). Of these, 54 reported testing positive for COVID-19, and 279 reported testing negative.

Sleep and activity were significantly different for the positive and negative groups, with an AUC of 0.68 (IQR, 0.57-0.79) for the sleep metric and 0.69 (IQR, 0.61-0.77) for the activity metric, suggesting that these parameters were more affected in COVID-19–positive participants.

When the investigators combined resting heart rate, sleep, and activity into a single metric, predictive performance improved to an AUC of 0.72 (IQR, 0.64-0.80).

The next step, Dr. Quer said, is to include an alert to notify users of possible infection.
 

Alerting users to possible COVID-19 infection

In a similar study, an alert feature was already incorporated. The study, led by Michael P. Snyder, PhD, director of the Center for Genomics and Personalized Medicine at Stanford (Calif.) University, will soon be published online in Nature Biomedical Engineering. In that study, presymptomatic detection of COVID-19 was achieved in more than 80% of participants using resting heart rate.

“The median is 4 days prior to symptom formation,” Dr. Snyder said in an interview. “We have an alarm system to notify people when their heart rate is elevated. So a positive signal from a smartwatch can be used to follow up by polymerase chain reaction [testing].”

Dr. Snyder said these approaches offer a roadmap to containing widespread infections. “Public health authorities need to be open to these technologies and begin incorporating them into their tracking,” he said. “Right now, people do temperature checks, which are of limited value. Resting heart rate is much better information.”

Although the DETECT researchers have not yet received feedback on their results, they believe public health authorities could recommend the use of such apps. “These are devices that people routinely wear for tracking their fitness and sleep, so it would be relatively easy to use the data for viral illness tracking,” said co–lead author Jennifer Radin, PhD, an epidemiologist at Scripps. “Testing resources are still limited and don’t allow for routine serial testing of individuals who may be asymptomatic or presymptomatic. Wearables can offer a different way to routinely monitor and screen people for changes in their data that may indicate COVID-19.”

The marshaling of data through consumer digital platforms to fight the coronavirus is gaining ground. New York State and New Jersey are already embracing smartphone apps to alert individuals to possible exposure to the virus.

More than 710,000 New Yorkers have downloaded the COVID NY Alert app, launched in October to help protect individuals and communities from COVID-19 by sending alerts without compromising privacy or personal information. “Upon receiving a notification about a potential exposure, users are then able to self-quarantine, get tested, and reduce the potential exposure risk to family, friends, coworkers, and others,” Jonah Bruno, a spokesperson for the New York State Department of Health, said in an interview.

And recently the Mayo Clinic and Safe Health Systems launched a platform to store COVID-19 testing and vaccination data.

Both the Scripps and Stanford platforms are part of a global technologic response to the COVID-19 pandemic. Prospective studies, led by device manufacturers and academic institutions, allow individuals to voluntarily share sensor and clinical data to address the crisis. Similar approaches have been used to track COVID-19 in large populations in Germany via the Corona Data Donation app.

The study by Dr. Quer and colleagues was funded by a grant from the National Center for Advancing Translational Sciences at the National Institutes of Health. One coauthor reported grants from Janssen and personal fees from Otsuka and Livongo outside of the submitted work. The other authors have disclosed no relevant financial relationships. Dr. Snyder has ties to Personalis, Qbio, January, SensOmics, Protos, Mirvie, and Oralome.
 

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

Editors in chief at 10 leading family medicine journals have banded together to address systemic racism in research, health care, and the medical profession.

Sumi Sexton, MD, editor in chief of American Family Physician (AFP), said in an interview she had been working on changes at her journal that would answer the need for action that was made clear by this summer’s Black Lives Matter protests and realized the issue was much bigger than one journal. She proposed the collaboration with the other editors.

The editors wrote a joint statement explaining what they plan to do collectively. It was published online Oct. 15 ahead of print and will be published in all 10 journals at the beginning of the year.

Following the action by family medicine editors, the American College of Physicians issued a statement expressing commitment to being an antiracist organization. It calls on all doctors to speak out against hate and discrimination and to act against institutional and systemic racism. The statement also apologizes for the organization’s own past actions: “ACP acknowledges and regrets its own historical organizational injustices and inequities, and past racism, discrimination and exclusionary practices throughout its history, whether intentional or unintentional, by act or omission.”


 

Family medicine journals plan changes

Changes will differ at each family medicine publication, according to Sexton and other interviewees. Some specific changes at AFP, for example, include creating a medical editor role dedicated to diversity, equity, and inclusion to ensure that content is not only accurate but also that more content addresses racism, Dr. Sexton said.

AFP is creating a Web page dedicated to diversity and will now capitalize the word “Black” in racial and cultural references. Recent calls for papers have included emphasis on finding authors from underrepresented groups and on mentoring new authors.

“We really need to enable our colleagues,” Dr. Sexton said.

The journals are also pooling their published research on topics of racism and inclusion and have established a joint bibliography.

The steps are important, Dr. Sexton said, because reform in research will start a “cascade of action” that will result in better patient care.

“Our mission is to care for the individual as a whole person,” Dr. Sexton said. “This is part of that mission.”
 

Increasing diversity on editorial boards

Family physician Kameron Leigh Matthews, MD, chief medical officer for the Veterans Health Administration, praised the journals’ plan.

She noted that the groups are addressing diversity on their editorial boards, as well as evaluating content. Effective change must also happen regarding the people reviewing the content, she said in an interview. “It has to be both.

“I’m very proud as a family physician that our editors came together and are giving the right response. It’s not enough to say we stand against racism. They’re actually offering concrete actions that they will take as editors, and that will influence health care,” she said.

Dr. Matthews pointed to an example of what can happen when the editorial process fails and racism is introduced in research.

She cited the retraction of an article in the Journal of the American Heart Association entitled, “Evolution of Race and Ethnicity Considerations for the Cardiology Workforce.” The article advocated for ending racial and ethnic preferences in undergraduate and medical school admissions.

The American Heart Association said the article concluded “incorrectly that Black and Hispanic trainees in medicine are less qualified than White and Asian trainees.” The article had “rightfully drawn criticism for its misrepresentations and conclusions,” the AHA said, adding that it would launch an investigation into how the article came to be published.

Dr. Matthews says that’s why it’s so important that, in their statement, the family medicine editors vow to address not only the content but also the editing process to avoid similar systemic lapses.

Dr. Matthews added that, because the proportion of physicians from underrepresented groups is small – only 5% of physicians are Black and 6% are Hispanic – it is vital, as recommended in the editors’ statement, to mentor researchers from underrepresented groups and to reach out to students and residents to be coauthors.

“To sit back and say there’s not enough to recruit from is not sufficient,” Dr. Matthews said. “You need to recognize that you need to assist with expanding the pool.”

She also said she would like to see the journals focus more heavily on solutions to racial disparities in health care rather than on pointing them out.

At the Journal of Family Practice (JFP), Editor in Chief John Hickner, MD, said adding diversity to the editorial board is a top priority. He also reiterated that diversity in top leadership is a concern across all the journals, inasmuch as only 1 of the 10 editors in chief is a person of color.

As an editor, he said, he will personally, as well as through family medicine department chairs, be seeking authors who are members of underrepresented groups and that he will be assisting those who need help.

“I’m committed to giving them special attention in the editorial process,” he said.

Dr. Hickner said the 10 journals have also committed to periodically evaluate whether their approaches are making substantial changes. He said the editors have vowed to meet at least once a year to review progress “and hold each other accountable.”

Statement authors, in addition to Dr. Sexton and Dr. Hickner, include these editors in chief: Caroline R. Richardson, MD, Annals of Family Medicine; Sarina B. Schrager, MD, FPM; Marjorie A. Bowman, MD, The Journal of the American Board of Family Medicine; Christopher P. Morley, PhD, PRiMER; Nicholas Pimlott, MD, PhD, Canadian Family Physician; John W. Saultz, MD, Family Medicine; and Barry D. Weiss, MD, FP Essentials.

The authors have disclosed no relevant financial relationships. The Journal of Family Practice is owned by the same news organization as this publication.
 

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

Editors in chief at 10 leading family medicine journals have banded together to address systemic racism in research, health care, and the medical profession.

Sumi Sexton, MD, editor in chief of American Family Physician (AFP), said in an interview she had been working on changes at her journal that would answer the need for action that was made clear by this summer’s Black Lives Matter protests and realized the issue was much bigger than one journal. She proposed the collaboration with the other editors.

The editors wrote a joint statement explaining what they plan to do collectively. It was published online Oct. 15 ahead of print and will be published in all 10 journals at the beginning of the year.

Following the action by family medicine editors, the American College of Physicians issued a statement expressing commitment to being an antiracist organization. It calls on all doctors to speak out against hate and discrimination and to act against institutional and systemic racism. The statement also apologizes for the organization’s own past actions: “ACP acknowledges and regrets its own historical organizational injustices and inequities, and past racism, discrimination and exclusionary practices throughout its history, whether intentional or unintentional, by act or omission.”


 

Family medicine journals plan changes

Changes will differ at each family medicine publication, according to Sexton and other interviewees. Some specific changes at AFP, for example, include creating a medical editor role dedicated to diversity, equity, and inclusion to ensure that content is not only accurate but also that more content addresses racism, Dr. Sexton said.

AFP is creating a Web page dedicated to diversity and will now capitalize the word “Black” in racial and cultural references. Recent calls for papers have included emphasis on finding authors from underrepresented groups and on mentoring new authors.

“We really need to enable our colleagues,” Dr. Sexton said.

The journals are also pooling their published research on topics of racism and inclusion and have established a joint bibliography.

The steps are important, Dr. Sexton said, because reform in research will start a “cascade of action” that will result in better patient care.

“Our mission is to care for the individual as a whole person,” Dr. Sexton said. “This is part of that mission.”
 

Increasing diversity on editorial boards

Family physician Kameron Leigh Matthews, MD, chief medical officer for the Veterans Health Administration, praised the journals’ plan.

She noted that the groups are addressing diversity on their editorial boards, as well as evaluating content. Effective change must also happen regarding the people reviewing the content, she said in an interview. “It has to be both.

“I’m very proud as a family physician that our editors came together and are giving the right response. It’s not enough to say we stand against racism. They’re actually offering concrete actions that they will take as editors, and that will influence health care,” she said.

Dr. Matthews pointed to an example of what can happen when the editorial process fails and racism is introduced in research.

She cited the retraction of an article in the Journal of the American Heart Association entitled, “Evolution of Race and Ethnicity Considerations for the Cardiology Workforce.” The article advocated for ending racial and ethnic preferences in undergraduate and medical school admissions.

The American Heart Association said the article concluded “incorrectly that Black and Hispanic trainees in medicine are less qualified than White and Asian trainees.” The article had “rightfully drawn criticism for its misrepresentations and conclusions,” the AHA said, adding that it would launch an investigation into how the article came to be published.

Dr. Matthews says that’s why it’s so important that, in their statement, the family medicine editors vow to address not only the content but also the editing process to avoid similar systemic lapses.

Dr. Matthews added that, because the proportion of physicians from underrepresented groups is small – only 5% of physicians are Black and 6% are Hispanic – it is vital, as recommended in the editors’ statement, to mentor researchers from underrepresented groups and to reach out to students and residents to be coauthors.

“To sit back and say there’s not enough to recruit from is not sufficient,” Dr. Matthews said. “You need to recognize that you need to assist with expanding the pool.”

She also said she would like to see the journals focus more heavily on solutions to racial disparities in health care rather than on pointing them out.

At the Journal of Family Practice (JFP), Editor in Chief John Hickner, MD, said adding diversity to the editorial board is a top priority. He also reiterated that diversity in top leadership is a concern across all the journals, inasmuch as only 1 of the 10 editors in chief is a person of color.

As an editor, he said, he will personally, as well as through family medicine department chairs, be seeking authors who are members of underrepresented groups and that he will be assisting those who need help.

“I’m committed to giving them special attention in the editorial process,” he said.

Dr. Hickner said the 10 journals have also committed to periodically evaluate whether their approaches are making substantial changes. He said the editors have vowed to meet at least once a year to review progress “and hold each other accountable.”

Statement authors, in addition to Dr. Sexton and Dr. Hickner, include these editors in chief: Caroline R. Richardson, MD, Annals of Family Medicine; Sarina B. Schrager, MD, FPM; Marjorie A. Bowman, MD, The Journal of the American Board of Family Medicine; Christopher P. Morley, PhD, PRiMER; Nicholas Pimlott, MD, PhD, Canadian Family Physician; John W. Saultz, MD, Family Medicine; and Barry D. Weiss, MD, FP Essentials.

The authors have disclosed no relevant financial relationships. The Journal of Family Practice is owned by the same news organization as this publication.
 

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

Editors in chief at 10 leading family medicine journals have banded together to address systemic racism in research, health care, and the medical profession.

Sumi Sexton, MD, editor in chief of American Family Physician (AFP), said in an interview she had been working on changes at her journal that would answer the need for action that was made clear by this summer’s Black Lives Matter protests and realized the issue was much bigger than one journal. She proposed the collaboration with the other editors.

The editors wrote a joint statement explaining what they plan to do collectively. It was published online Oct. 15 ahead of print and will be published in all 10 journals at the beginning of the year.

Following the action by family medicine editors, the American College of Physicians issued a statement expressing commitment to being an antiracist organization. It calls on all doctors to speak out against hate and discrimination and to act against institutional and systemic racism. The statement also apologizes for the organization’s own past actions: “ACP acknowledges and regrets its own historical organizational injustices and inequities, and past racism, discrimination and exclusionary practices throughout its history, whether intentional or unintentional, by act or omission.”


 

Family medicine journals plan changes

Changes will differ at each family medicine publication, according to Sexton and other interviewees. Some specific changes at AFP, for example, include creating a medical editor role dedicated to diversity, equity, and inclusion to ensure that content is not only accurate but also that more content addresses racism, Dr. Sexton said.

AFP is creating a Web page dedicated to diversity and will now capitalize the word “Black” in racial and cultural references. Recent calls for papers have included emphasis on finding authors from underrepresented groups and on mentoring new authors.

“We really need to enable our colleagues,” Dr. Sexton said.

The journals are also pooling their published research on topics of racism and inclusion and have established a joint bibliography.

The steps are important, Dr. Sexton said, because reform in research will start a “cascade of action” that will result in better patient care.

“Our mission is to care for the individual as a whole person,” Dr. Sexton said. “This is part of that mission.”
 

Increasing diversity on editorial boards

Family physician Kameron Leigh Matthews, MD, chief medical officer for the Veterans Health Administration, praised the journals’ plan.

She noted that the groups are addressing diversity on their editorial boards, as well as evaluating content. Effective change must also happen regarding the people reviewing the content, she said in an interview. “It has to be both.

“I’m very proud as a family physician that our editors came together and are giving the right response. It’s not enough to say we stand against racism. They’re actually offering concrete actions that they will take as editors, and that will influence health care,” she said.

Dr. Matthews pointed to an example of what can happen when the editorial process fails and racism is introduced in research.

She cited the retraction of an article in the Journal of the American Heart Association entitled, “Evolution of Race and Ethnicity Considerations for the Cardiology Workforce.” The article advocated for ending racial and ethnic preferences in undergraduate and medical school admissions.

The American Heart Association said the article concluded “incorrectly that Black and Hispanic trainees in medicine are less qualified than White and Asian trainees.” The article had “rightfully drawn criticism for its misrepresentations and conclusions,” the AHA said, adding that it would launch an investigation into how the article came to be published.

Dr. Matthews says that’s why it’s so important that, in their statement, the family medicine editors vow to address not only the content but also the editing process to avoid similar systemic lapses.

Dr. Matthews added that, because the proportion of physicians from underrepresented groups is small – only 5% of physicians are Black and 6% are Hispanic – it is vital, as recommended in the editors’ statement, to mentor researchers from underrepresented groups and to reach out to students and residents to be coauthors.

“To sit back and say there’s not enough to recruit from is not sufficient,” Dr. Matthews said. “You need to recognize that you need to assist with expanding the pool.”

She also said she would like to see the journals focus more heavily on solutions to racial disparities in health care rather than on pointing them out.

At the Journal of Family Practice (JFP), Editor in Chief John Hickner, MD, said adding diversity to the editorial board is a top priority. He also reiterated that diversity in top leadership is a concern across all the journals, inasmuch as only 1 of the 10 editors in chief is a person of color.

As an editor, he said, he will personally, as well as through family medicine department chairs, be seeking authors who are members of underrepresented groups and that he will be assisting those who need help.

“I’m committed to giving them special attention in the editorial process,” he said.

Dr. Hickner said the 10 journals have also committed to periodically evaluate whether their approaches are making substantial changes. He said the editors have vowed to meet at least once a year to review progress “and hold each other accountable.”

Statement authors, in addition to Dr. Sexton and Dr. Hickner, include these editors in chief: Caroline R. Richardson, MD, Annals of Family Medicine; Sarina B. Schrager, MD, FPM; Marjorie A. Bowman, MD, The Journal of the American Board of Family Medicine; Christopher P. Morley, PhD, PRiMER; Nicholas Pimlott, MD, PhD, Canadian Family Physician; John W. Saultz, MD, Family Medicine; and Barry D. Weiss, MD, FP Essentials.

The authors have disclosed no relevant financial relationships. The Journal of Family Practice is owned by the same news organization as this publication.
 

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

The latest recommendations from sports cardiologists on getting athletes with COVID-19 back on the playing field safely emphasize a more judicious approach to screening for cardiac injury.

The new recommendations, made by the American College of Cardiology’s Sports and Exercise Cardiology Section, are for adult athletes in competitive sports and also for two important groups: younger athletes taking part in competitive high school sports and older athletes aged 35 and older, the Masters athletes, who continue to be active throughout their lives. The document was published online in JAMA Cardiology.

Because of the evolving nature of knowledge about COVID-19, updates on recommendations for safe return to play for athletes of all ages will continue to be made, senior author Aaron L. Baggish, MD, director of the cardiovascular performance program at Massachusetts General Hospital, Boston, said.

“The recommendations we released in May were entirely based on our experience taking care of hospitalized patients with COVID-19; we had no athletes in this population. We used a lot of conservative guesswork around how this would apply to otherwise healthy athletes,” Dr. Baggish said in an interview.

“But as sports started to open up, and we started to see large numbers of first professional and then college athletes come back into training, we realized that we needed to stop and ask whether the recommendations we put forward back in May were still appropriate,” Dr. Baggish said.

“Once we started to actually get into the trenches with these athletes, literally hundreds of them, and applying the testing strategies that we had initially recommended in everybody, we realized that we probably had some room for improvement, and that’s why we reconvened, to make these revisions,” he said.

Essentially, the recommendations now urge less cardiac testing. “Cardiac injury is not as common as we may have originally thought,” said Dr. Baggish.

“In the early days of COVID, people who were hospitalized had evidence of heart injury, and so we wondered if that prevalence would also be applicable to otherwise young, healthy people who got COVID. If that had been the case, we would have been in big trouble with respect to getting people back into sports. So this is why we started with a conservative screening approach and a lot of testing in order to not miss a huge burden of disease,” he said.

“But what we’ve learned over the past few months is that young people who get either asymptomatic or mild infection appear to have very, very low risk of having associated heart injury, so the need for testing in that population, when people who have infections recover fully, is almost certainly not going to be high yield,” Dr. Baggish said.
 

First iteration of the recommendations

Published in May in the early weeks of the pandemic, the first recommendations for safe return to play said that all athletes should stop training for at least 2 weeks after their symptoms resolve, then undergo “careful, clinical cardiovascular evaluation in combination with cardiac biomarkers and imaging.”

Additional testing with cardiac MRI, exercise testing, or ambulatory rhythm monitoring was to be done “based on the clinical course and initial testing.”

But experts caution that monitoring on such a scale in everyone is unnecessary and could even be counterproductive.

“Sending young athletes for extensive testing is not warranted and could send them to unnecessary testing, cardiac imaging, and so on,” Dr. Baggish said.

Only those athletes who continue to have symptoms or whose symptoms return when they get back to their athletic activities should go on for more screening.

“There, in essence, is the single main change from May, and that is a move away from screening with testing everyone, [and instead] confining that to the people who had moderate or greater severity disease,” he said.

Both iterations of the recommendations end with the same message.

“We are at the beginning of our knowledge about the cardiotoxic effects of COVID-19 but we are gathering evidence every day,” said Dr. Baggish. “Just as they did earlier, we acknowledge that our approaches are subject to change when we learn more about how COVID affects the heart, and specifically the hearts of athletes. This will be an ongoing process.”
 

Something to lean on

The recommendations are welcome, said James E. Udelson, MD, chief of the division of cardiology at Tufts Medical Center, Boston, coauthor of an accompanying editorial.

“It was a bit of the wild west out there, because each university, each college, all with good intentions, had been all struggling to figure out what to do, and how much to do. Probably the most important message from this new paper is the fact that now there is something out there that all coaches, athletes, families, schools, trainers can get some guidance from,” Dr. Udelson said in an interview.

Refining the cardiac screening criteria was a necessary step, Dr. Udelson said.

“How much cardiac imaging do you do? That is a matter of controversy,” said Dr. Udelson, who coauthored the commentary with Tufts cardiologist Ethan Rowin, MD, and Michael A. Curtis, MEd, a certified strength and conditioning specialist at the University of Virginia, Charlottesville. “The problem is that if you use a very sensitive imaging test on a lot of people, sometimes you find things that you really didn’t need to know about. They’re really not important. And now, the athlete is told he or she cannot play for 3 months because they might have myocarditis.

“Should we be too sensitive, meaning do we want to pick up anything no matter whether it’s important or not?” he added. “There will be a lot of false positives, and we are going to disqualify a lot of people. Or do you tune it a different way?”

Dr. Udelson said he would like to see commercial sports donate money to support research into the potential cardiotoxicity of COVID-19.

“If the organizations that benefit from these athletes, like the National Collegiate Athletic Association and professional sports leagues, can fund some of this research, that would be a huge help,” Dr. Udelson said.

“These are the top sports cardiologists in the country, and they have to start somewhere, and these are all based on what we know right now, as well as their own extensive experience. We all know that we are just at the beginning of our knowledge of this. But we have to have something to guide this huge community out there that is really thirsty for help.”

Dr. Baggish reports receiving research funding for the study of athletes in competitive sports from the National Heart, Lung, and Blood Institute; the National Football League Players Association; and the American Heart Association and receiving compensation for his role as team cardiologist from the US Olympic Committee/US Olympic Training Centers, US Soccer, US Rowing, the New England Patriots, the Boston Bruins, the New England Revolution, and Harvard University. Dr. Udelson has disclosed no relevant financial relationships.
 

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

The latest recommendations from sports cardiologists on getting athletes with COVID-19 back on the playing field safely emphasize a more judicious approach to screening for cardiac injury.

The new recommendations, made by the American College of Cardiology’s Sports and Exercise Cardiology Section, are for adult athletes in competitive sports and also for two important groups: younger athletes taking part in competitive high school sports and older athletes aged 35 and older, the Masters athletes, who continue to be active throughout their lives. The document was published online in JAMA Cardiology.

Because of the evolving nature of knowledge about COVID-19, updates on recommendations for safe return to play for athletes of all ages will continue to be made, senior author Aaron L. Baggish, MD, director of the cardiovascular performance program at Massachusetts General Hospital, Boston, said.

“The recommendations we released in May were entirely based on our experience taking care of hospitalized patients with COVID-19; we had no athletes in this population. We used a lot of conservative guesswork around how this would apply to otherwise healthy athletes,” Dr. Baggish said in an interview.

“But as sports started to open up, and we started to see large numbers of first professional and then college athletes come back into training, we realized that we needed to stop and ask whether the recommendations we put forward back in May were still appropriate,” Dr. Baggish said.

“Once we started to actually get into the trenches with these athletes, literally hundreds of them, and applying the testing strategies that we had initially recommended in everybody, we realized that we probably had some room for improvement, and that’s why we reconvened, to make these revisions,” he said.

Essentially, the recommendations now urge less cardiac testing. “Cardiac injury is not as common as we may have originally thought,” said Dr. Baggish.

“In the early days of COVID, people who were hospitalized had evidence of heart injury, and so we wondered if that prevalence would also be applicable to otherwise young, healthy people who got COVID. If that had been the case, we would have been in big trouble with respect to getting people back into sports. So this is why we started with a conservative screening approach and a lot of testing in order to not miss a huge burden of disease,” he said.

“But what we’ve learned over the past few months is that young people who get either asymptomatic or mild infection appear to have very, very low risk of having associated heart injury, so the need for testing in that population, when people who have infections recover fully, is almost certainly not going to be high yield,” Dr. Baggish said.
 

First iteration of the recommendations

Published in May in the early weeks of the pandemic, the first recommendations for safe return to play said that all athletes should stop training for at least 2 weeks after their symptoms resolve, then undergo “careful, clinical cardiovascular evaluation in combination with cardiac biomarkers and imaging.”

Additional testing with cardiac MRI, exercise testing, or ambulatory rhythm monitoring was to be done “based on the clinical course and initial testing.”

But experts caution that monitoring on such a scale in everyone is unnecessary and could even be counterproductive.

“Sending young athletes for extensive testing is not warranted and could send them to unnecessary testing, cardiac imaging, and so on,” Dr. Baggish said.

Only those athletes who continue to have symptoms or whose symptoms return when they get back to their athletic activities should go on for more screening.

“There, in essence, is the single main change from May, and that is a move away from screening with testing everyone, [and instead] confining that to the people who had moderate or greater severity disease,” he said.

Both iterations of the recommendations end with the same message.

“We are at the beginning of our knowledge about the cardiotoxic effects of COVID-19 but we are gathering evidence every day,” said Dr. Baggish. “Just as they did earlier, we acknowledge that our approaches are subject to change when we learn more about how COVID affects the heart, and specifically the hearts of athletes. This will be an ongoing process.”
 

Something to lean on

The recommendations are welcome, said James E. Udelson, MD, chief of the division of cardiology at Tufts Medical Center, Boston, coauthor of an accompanying editorial.

“It was a bit of the wild west out there, because each university, each college, all with good intentions, had been all struggling to figure out what to do, and how much to do. Probably the most important message from this new paper is the fact that now there is something out there that all coaches, athletes, families, schools, trainers can get some guidance from,” Dr. Udelson said in an interview.

Refining the cardiac screening criteria was a necessary step, Dr. Udelson said.

“How much cardiac imaging do you do? That is a matter of controversy,” said Dr. Udelson, who coauthored the commentary with Tufts cardiologist Ethan Rowin, MD, and Michael A. Curtis, MEd, a certified strength and conditioning specialist at the University of Virginia, Charlottesville. “The problem is that if you use a very sensitive imaging test on a lot of people, sometimes you find things that you really didn’t need to know about. They’re really not important. And now, the athlete is told he or she cannot play for 3 months because they might have myocarditis.

“Should we be too sensitive, meaning do we want to pick up anything no matter whether it’s important or not?” he added. “There will be a lot of false positives, and we are going to disqualify a lot of people. Or do you tune it a different way?”

Dr. Udelson said he would like to see commercial sports donate money to support research into the potential cardiotoxicity of COVID-19.

“If the organizations that benefit from these athletes, like the National Collegiate Athletic Association and professional sports leagues, can fund some of this research, that would be a huge help,” Dr. Udelson said.

“These are the top sports cardiologists in the country, and they have to start somewhere, and these are all based on what we know right now, as well as their own extensive experience. We all know that we are just at the beginning of our knowledge of this. But we have to have something to guide this huge community out there that is really thirsty for help.”

Dr. Baggish reports receiving research funding for the study of athletes in competitive sports from the National Heart, Lung, and Blood Institute; the National Football League Players Association; and the American Heart Association and receiving compensation for his role as team cardiologist from the US Olympic Committee/US Olympic Training Centers, US Soccer, US Rowing, the New England Patriots, the Boston Bruins, the New England Revolution, and Harvard University. Dr. Udelson has disclosed no relevant financial relationships.
 

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

The latest recommendations from sports cardiologists on getting athletes with COVID-19 back on the playing field safely emphasize a more judicious approach to screening for cardiac injury.

The new recommendations, made by the American College of Cardiology’s Sports and Exercise Cardiology Section, are for adult athletes in competitive sports and also for two important groups: younger athletes taking part in competitive high school sports and older athletes aged 35 and older, the Masters athletes, who continue to be active throughout their lives. The document was published online in JAMA Cardiology.

Because of the evolving nature of knowledge about COVID-19, updates on recommendations for safe return to play for athletes of all ages will continue to be made, senior author Aaron L. Baggish, MD, director of the cardiovascular performance program at Massachusetts General Hospital, Boston, said.

“The recommendations we released in May were entirely based on our experience taking care of hospitalized patients with COVID-19; we had no athletes in this population. We used a lot of conservative guesswork around how this would apply to otherwise healthy athletes,” Dr. Baggish said in an interview.

“But as sports started to open up, and we started to see large numbers of first professional and then college athletes come back into training, we realized that we needed to stop and ask whether the recommendations we put forward back in May were still appropriate,” Dr. Baggish said.

“Once we started to actually get into the trenches with these athletes, literally hundreds of them, and applying the testing strategies that we had initially recommended in everybody, we realized that we probably had some room for improvement, and that’s why we reconvened, to make these revisions,” he said.

Essentially, the recommendations now urge less cardiac testing. “Cardiac injury is not as common as we may have originally thought,” said Dr. Baggish.

“In the early days of COVID, people who were hospitalized had evidence of heart injury, and so we wondered if that prevalence would also be applicable to otherwise young, healthy people who got COVID. If that had been the case, we would have been in big trouble with respect to getting people back into sports. So this is why we started with a conservative screening approach and a lot of testing in order to not miss a huge burden of disease,” he said.

“But what we’ve learned over the past few months is that young people who get either asymptomatic or mild infection appear to have very, very low risk of having associated heart injury, so the need for testing in that population, when people who have infections recover fully, is almost certainly not going to be high yield,” Dr. Baggish said.
 

First iteration of the recommendations

Published in May in the early weeks of the pandemic, the first recommendations for safe return to play said that all athletes should stop training for at least 2 weeks after their symptoms resolve, then undergo “careful, clinical cardiovascular evaluation in combination with cardiac biomarkers and imaging.”

Additional testing with cardiac MRI, exercise testing, or ambulatory rhythm monitoring was to be done “based on the clinical course and initial testing.”

But experts caution that monitoring on such a scale in everyone is unnecessary and could even be counterproductive.

“Sending young athletes for extensive testing is not warranted and could send them to unnecessary testing, cardiac imaging, and so on,” Dr. Baggish said.

Only those athletes who continue to have symptoms or whose symptoms return when they get back to their athletic activities should go on for more screening.

“There, in essence, is the single main change from May, and that is a move away from screening with testing everyone, [and instead] confining that to the people who had moderate or greater severity disease,” he said.

Both iterations of the recommendations end with the same message.

“We are at the beginning of our knowledge about the cardiotoxic effects of COVID-19 but we are gathering evidence every day,” said Dr. Baggish. “Just as they did earlier, we acknowledge that our approaches are subject to change when we learn more about how COVID affects the heart, and specifically the hearts of athletes. This will be an ongoing process.”
 

Something to lean on

The recommendations are welcome, said James E. Udelson, MD, chief of the division of cardiology at Tufts Medical Center, Boston, coauthor of an accompanying editorial.

“It was a bit of the wild west out there, because each university, each college, all with good intentions, had been all struggling to figure out what to do, and how much to do. Probably the most important message from this new paper is the fact that now there is something out there that all coaches, athletes, families, schools, trainers can get some guidance from,” Dr. Udelson said in an interview.

Refining the cardiac screening criteria was a necessary step, Dr. Udelson said.

“How much cardiac imaging do you do? That is a matter of controversy,” said Dr. Udelson, who coauthored the commentary with Tufts cardiologist Ethan Rowin, MD, and Michael A. Curtis, MEd, a certified strength and conditioning specialist at the University of Virginia, Charlottesville. “The problem is that if you use a very sensitive imaging test on a lot of people, sometimes you find things that you really didn’t need to know about. They’re really not important. And now, the athlete is told he or she cannot play for 3 months because they might have myocarditis.

“Should we be too sensitive, meaning do we want to pick up anything no matter whether it’s important or not?” he added. “There will be a lot of false positives, and we are going to disqualify a lot of people. Or do you tune it a different way?”

Dr. Udelson said he would like to see commercial sports donate money to support research into the potential cardiotoxicity of COVID-19.

“If the organizations that benefit from these athletes, like the National Collegiate Athletic Association and professional sports leagues, can fund some of this research, that would be a huge help,” Dr. Udelson said.

“These are the top sports cardiologists in the country, and they have to start somewhere, and these are all based on what we know right now, as well as their own extensive experience. We all know that we are just at the beginning of our knowledge of this. But we have to have something to guide this huge community out there that is really thirsty for help.”

Dr. Baggish reports receiving research funding for the study of athletes in competitive sports from the National Heart, Lung, and Blood Institute; the National Football League Players Association; and the American Heart Association and receiving compensation for his role as team cardiologist from the US Olympic Committee/US Olympic Training Centers, US Soccer, US Rowing, the New England Patriots, the Boston Bruins, the New England Revolution, and Harvard University. Dr. Udelson has disclosed no relevant financial relationships.
 

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

Clarissa Barnes, MD, a hospitalist at Avera McKennan Hospital in Sioux Falls, S.D., and until recently medical director of Avera’s LIGHT Program, a wellness-oriented service for doctors, nurse practitioners, and physician assistants, watched the COVID-19 crisis unfold up close in her community and her hospital. Sioux Falls traced its surge of COVID patients to an outbreak at a local meatpacking plant.

“In the beginning, we didn’t know much about the virus and its communicability, although we have since gotten a better handle on that,” she said. “We had questions: Should we give patients more fluids – or less? Steroids or not? In my experience as a hospitalist I never had patients die every day on my shift, but that was happening with COVID.” The crisis imposed serious stresses on frontline providers, and hospitalists were concerned about personal safety and exposure risk – not just for themselves but for their families.

“The first time I worked on the COVID unit, I moved into the guest room in our home, apart from my husband and our young children,” Dr. Barnes said. “Ultimately I caught the virus, although I have since recovered.” Her experience has highlighted how existing issues of job stress and burnout in hospital medicine have been exacerbated by COVID-19. Even physicians who consider themselves healthy may have little emotional reserve to draw upon in a crisis of this magnitude.

“We are social distancing at work, wearing masks, not eating together with our colleagues – with less camaraderie and social support than we used to have,” she said. “I feel exhausted and there’s no question that my colleagues and I have sacrificed a lot to deal with the pandemic.” Add to that the second front of the COVID-19 crisis, Dr. Barnes said, which is “fighting the medical information wars, trying to correct misinformation put out there by people. Physicians who have been on the front lines of the pandemic know how demoralizing it can be to have people negate your first-hand experience.”

The situation has gotten better in Sioux Falls, Dr. Barnes said, although cases have started rising in the state again. The stress, while not gone, is reduced. For some doctors, “COVID reminded us of why we do what we do. Some of the usual bureaucratic requirements were set aside and we could focus on what our patients needed and how to take care of them.”
 

Taking job stress seriously

Tiffani Panek, MA, SFHM, CLHM, administrator of the division of hospital medicine at Johns Hopkins Bayview Medical Center in Baltimore, said job stress is a major issue for hospitalist groups.

“We take it seriously here, and use a survey tool to measure morale in our group annually,” she said. “So far, knock on wood, Baltimore has not been one of the big hot spots, but we’ve definitely had waves of COVID patients.”

The Bayview hospitalist group has a diversified set of leaders, including a wellness director. “They’re always checking up on our people, keeping an eye on those who are most vulnerable. One of the stressors we hadn’t thought about before was for our people who live alone. With the isolation and lockdown, they haven’t been able to socialize, so we’ve made direct outreach, asking people how they were doing,” Ms. Panek said. “People know we’ve got their back – professionally and personally. They know, if there’s something we can do to help, we will do it.”

Bayview Medical Center has COVID-specific units and non-COVID units, and has tried to rotate hospitalist assignments because more than a couple days in a row spent wearing full personal protective equipment (PPE) is exhausting, Ms. Panek said. The group also allocated a respite room just outside the biocontainment unit, with a computer and opportunities for providers to just sit and take a breather – with appropriate social distancing. “It’s not fancy, but you just have to wear a mask, not full PPE.”

The Hopkins hospitalist group’s wellness director, Catherine Washburn, MD, also a working hospitalist, said providers are exhausted, and trying to transition to the new normal is a moving target.

“It’s hard for anyone to say what our lives will look like in 6 months,” she said. “People in our group have lost family members to COVID, or postponed major life events, like weddings. We acknowledge losses together as a group, and celebrate things worth celebrating, like babies or birthdays.”
 

Greatest COVID caseload

Joshua Case, MD, hospitalist medical director for 16 acute care hospitals of Northwell Health serving metropolitan New York City and Long Island, said his group’s hospitalists and other staff worked incredibly hard during the surge of COVID-19 patients in New York. “Northwell likely cared for more COVID patients than any other health care system in the U.S., if not the world.

“It’s vastly different now. We went from a peak of thousands of cases per day down to about 70-90 new cases a day across our system. We’re lucky our system recognized that COVID could be an issue early on, with all of the multifaceted stressors on patient care,” Dr. Case said. “We’ve done whatever we could to give people time off, especially as the census started to come down. We freed up as many supportive mental health services as we could, working with the health system’s employee assistance program.”

Northwell gave out numbers for the psychiatry department, with clinicians available 24/7 for a confidential call, along with outside volunteers and a network of trauma psychologists. “Our system also provided emergency child care for staff, including hospitalists, wherever we could, drawing upon community resources,” Dr. Case added.

“We recognize that we’re all in the same foxhole. That’s been a helpful attitude – recognizing that it’s okay to be upset in a crisis and to have trouble dealing with what’s going on,” he said. “We need to acknowledge that some of us are suffering and try to encourage people to face it head on. For a lot of physicians, especially those who were redeployed here from other departments, it was important just to have us ask if they were doing okay.”

Brian Schroeder, MHA, FACHE, FHM, assistant vice president for hospital and emergency medicine for Atrium Health, based in Charlotte, N.C., said one of the biggest sources of stress on his staff has been the constant pace of change – whether local hospital protocols, state policies, or guidelines from the Centers for Disease Control and Prevention. “The updating is difficult to keep up with. A lot of our physicians get worried and anxious that they’re not following the latest guidelines or correctly doing what they should be doing to care for COVID patients. One thing we’ve done to alleviate some of that fear and anxiety is through weekly huddles with our hospital teams, focusing on changes relevant to their work. We also have weekly ‘all-hands’ meetings for our 250 providers across 13 acute and four postacute facilities.”

Before COVID, it was difficult to get everyone together as one big group from hospitals up to 5 hours apart, but with the Microsoft Teams platform, they can all meet together.

“At the height of the pandemic, we’d convene weekly and share national statistics, organizational statistics, testing updates, changes to protocols,” Mr. Schroeder said. As the pace of change has slowed, these meetings were cut back to monthly. “Our physicians feel we are passing on information as soon as we get it. They know we’ll always tell them what we know.”

Sarah Richards, MD, assistant professor of internal medicine at the University of Nebraska, Omaha, who heads the Society of Hospital Medicine’s Well-Being Task Force, formed to address staff stress in the COVID environment, said there are things that health care systems can do to help mitigate job stress and burnout. But broader issues may need to be addressed at a national level. “SHM is trying to understand work-related stress – and to identify resources that could support doctors, so they can spend more of their time doing what they enjoy most, which is taking care of patients,” she said.

“We also recognize that people have had very different experiences, depending on geography, and at the individual level stressors are experienced very differently,” Dr. Richard noted. “One of the most common stressors we’ve heard from doctors is the challenge of caring for patients who are lonely and isolated in their hospital rooms, suffering and dying in new ways. In low-incidence areas, doctors are expressing guilt because they aren’t under as much stress as their colleagues. In high-incidence areas, doctors are already experiencing posttraumatic stress disorder.”

SHM’s Well-Being Task Force is working on a tool to help normalize these stressors and encourage open conversations about mental health issues. A guide called “HM COVID Check-in Guide for Self & Peers” is designed to help hospitalists break the culture of silence around well-being and burnout during COVID-19 and how people are handling and processing the pandemic experience. It is expected to be completed later this year, Dr. Richards said. Other SHM projects and resources for staff support are also in the works.
 

The impact on women doctors

In a recent Journal of Hospital Medicine article entitled “Collateral Damage: How COVID-19 is Adversely Impacting Women Physicians,” hospitalist Yemisi Jones, MD, medical director of continuing medical education at Cincinnati Children’s Hospital Medical Center, and colleagues argue that preexisting gender inequities in compensation, academic rank and leadership positions for physicians have made the COVID-19 crisis even more burdensome on female hospitalists.¹

“Increased childcare and schooling obligations, coupled with disproportionate household responsibilities and an inability to work from home, will likely result in female hospitalists struggling to meet family needs while pandemic-related work responsibilities are ramping up,” they write. COVID may intensify workplace inequalities, with a lack of recognition of the undue strain that group policies place on women.

“Often women suffer in silence,” said coauthor Jennifer O’Toole, MD, MEd, director of education in the division of hospital medicine at Cincinnati Children’s Hospital Medical Center and program director of the internal medicine–pediatrics residency. “We are not always the best self-advocates, although many of us are working on that.”

When women in hospital medicine take leadership roles, these often tend to involve mutual support activities, taking care of colleagues, and promoting collaborative work environments, Dr. Jones added. The stereotypical example is the committee that organizes celebrations when group members get married or have babies.

These activities can take a lot of time, she said. “We need to pay attention to that kind of role in our groups, because it’s important to the cohesiveness of the group. But it often goes unrecognized and doesn’t translate into the currency of promotion and leadership in medicine. When women go for promotions in the future, how will what happened during the COVID crisis impact their opportunities?”

What is the answer to overcoming these systemic inequities? Start with making sure women are part of the leadership team, with responsibilities for group policies, schedules, and other important decisions. “Look at your group’s leadership – particularly the higher positions. If it’s not diverse, ask why. ‘What is it about the structure of our group?’ Make a more concerted effort in your recruitment and retention,” Dr. Jones said.

The JHM article also recommends closely monitoring the direct and indirect effects of COVID-19 on female hospitalists, inquiring specifically about the needs of women in the organization, and ensuring that diversity, inclusion, and equity efforts are not suspended during the pandemic. Gender-based disparities in pay also need a closer look, and not just one time but reviewed periodically and adjusted accordingly.

Mentoring for early career women is important, but more so is sponsorship – someone in a high-level leadership role in the group sponsoring women who are rising up the career ladder, Dr. O’Toole said. “Professional women tend to be overmentored and undersponsored.”
 

What are the answers?

Ultimately, listening is key to try to help people get through the pandemic, Dr. Washburn said. “People become burned out when they feel leadership doesn’t understand their needs or doesn’t hear their concerns. Our group leaders all do clinical work, so they are seen as one of us. They try very hard; they have listening ears. But listening is just the first step. Next step is to work creatively to get the identified needs met.”

A few years ago, Johns Hopkins developed training in enhanced communication in health care for all hospital providers, including nurses and doctors, encouraging them to get trained in how to actively listen and address their patients’ emotional and social experiences as well as disease, Dr. Washburn explained. Learning how to listen better to patients can enhance skills at listening to colleagues, and vice versa. “We recognize the importance of better communication – for reducing sentinel events in the hospital and also for preventing staff burnout.”

Dr. Barnes also does physician coaching, and says a lot of that work is helping people achieve clarity on their core values. “Healing patients is a core identify for physicians; we want to take care of people. But other things can get in the way of that, and hospitalist groups can work at minimizing those barriers. We also need to learn, as hospitalists, that we work in a group. You need to be creative in how you do your team building, especially now, when you can no longer get together for dinner. Whatever it is, how do we bring our team back together? The biggest source of support for many hospitalists, beyond their family, is the group.”

Dr. Case said there is a longer-term need to study the root causes of burnout in hospitalists and to identify the issues that cause job stress. “What is modifiable? How can we tackle it? I see that as big part of my job every day. Being a physician is hard enough as it is. Let’s work to resolve those issues that add needlessly to the stress.”

“I think the pandemic brought a magnifying glass to how important a concern staff stress is,” Ms. Panek said. Resilience is important.

“We were working in our group on creating a culture that values trust and transparency, and then the COVID crisis hit,” she said. “But you can still keep working on those things. We would not have been as good or as positive as we were in managing this crisis without that preexisting culture to draw upon. We always said it was important. Now we know that’s true.”
 

Reference

1. Jones Y et al. Collateral Damage: How COVID-19 Is Adversely Impacting Women Physicians. J Hosp Med. 2020 August;15(8):507-9.

Clarissa Barnes, MD, a hospitalist at Avera McKennan Hospital in Sioux Falls, S.D., and until recently medical director of Avera’s LIGHT Program, a wellness-oriented service for doctors, nurse practitioners, and physician assistants, watched the COVID-19 crisis unfold up close in her community and her hospital. Sioux Falls traced its surge of COVID patients to an outbreak at a local meatpacking plant.

“In the beginning, we didn’t know much about the virus and its communicability, although we have since gotten a better handle on that,” she said. “We had questions: Should we give patients more fluids – or less? Steroids or not? In my experience as a hospitalist I never had patients die every day on my shift, but that was happening with COVID.” The crisis imposed serious stresses on frontline providers, and hospitalists were concerned about personal safety and exposure risk – not just for themselves but for their families.

“The first time I worked on the COVID unit, I moved into the guest room in our home, apart from my husband and our young children,” Dr. Barnes said. “Ultimately I caught the virus, although I have since recovered.” Her experience has highlighted how existing issues of job stress and burnout in hospital medicine have been exacerbated by COVID-19. Even physicians who consider themselves healthy may have little emotional reserve to draw upon in a crisis of this magnitude.

“We are social distancing at work, wearing masks, not eating together with our colleagues – with less camaraderie and social support than we used to have,” she said. “I feel exhausted and there’s no question that my colleagues and I have sacrificed a lot to deal with the pandemic.” Add to that the second front of the COVID-19 crisis, Dr. Barnes said, which is “fighting the medical information wars, trying to correct misinformation put out there by people. Physicians who have been on the front lines of the pandemic know how demoralizing it can be to have people negate your first-hand experience.”

The situation has gotten better in Sioux Falls, Dr. Barnes said, although cases have started rising in the state again. The stress, while not gone, is reduced. For some doctors, “COVID reminded us of why we do what we do. Some of the usual bureaucratic requirements were set aside and we could focus on what our patients needed and how to take care of them.”
 

Taking job stress seriously

Tiffani Panek, MA, SFHM, CLHM, administrator of the division of hospital medicine at Johns Hopkins Bayview Medical Center in Baltimore, said job stress is a major issue for hospitalist groups.

“We take it seriously here, and use a survey tool to measure morale in our group annually,” she said. “So far, knock on wood, Baltimore has not been one of the big hot spots, but we’ve definitely had waves of COVID patients.”

The Bayview hospitalist group has a diversified set of leaders, including a wellness director. “They’re always checking up on our people, keeping an eye on those who are most vulnerable. One of the stressors we hadn’t thought about before was for our people who live alone. With the isolation and lockdown, they haven’t been able to socialize, so we’ve made direct outreach, asking people how they were doing,” Ms. Panek said. “People know we’ve got their back – professionally and personally. They know, if there’s something we can do to help, we will do it.”

Bayview Medical Center has COVID-specific units and non-COVID units, and has tried to rotate hospitalist assignments because more than a couple days in a row spent wearing full personal protective equipment (PPE) is exhausting, Ms. Panek said. The group also allocated a respite room just outside the biocontainment unit, with a computer and opportunities for providers to just sit and take a breather – with appropriate social distancing. “It’s not fancy, but you just have to wear a mask, not full PPE.”

The Hopkins hospitalist group’s wellness director, Catherine Washburn, MD, also a working hospitalist, said providers are exhausted, and trying to transition to the new normal is a moving target.

“It’s hard for anyone to say what our lives will look like in 6 months,” she said. “People in our group have lost family members to COVID, or postponed major life events, like weddings. We acknowledge losses together as a group, and celebrate things worth celebrating, like babies or birthdays.”
 

Greatest COVID caseload

Joshua Case, MD, hospitalist medical director for 16 acute care hospitals of Northwell Health serving metropolitan New York City and Long Island, said his group’s hospitalists and other staff worked incredibly hard during the surge of COVID-19 patients in New York. “Northwell likely cared for more COVID patients than any other health care system in the U.S., if not the world.

“It’s vastly different now. We went from a peak of thousands of cases per day down to about 70-90 new cases a day across our system. We’re lucky our system recognized that COVID could be an issue early on, with all of the multifaceted stressors on patient care,” Dr. Case said. “We’ve done whatever we could to give people time off, especially as the census started to come down. We freed up as many supportive mental health services as we could, working with the health system’s employee assistance program.”

Northwell gave out numbers for the psychiatry department, with clinicians available 24/7 for a confidential call, along with outside volunteers and a network of trauma psychologists. “Our system also provided emergency child care for staff, including hospitalists, wherever we could, drawing upon community resources,” Dr. Case added.

“We recognize that we’re all in the same foxhole. That’s been a helpful attitude – recognizing that it’s okay to be upset in a crisis and to have trouble dealing with what’s going on,” he said. “We need to acknowledge that some of us are suffering and try to encourage people to face it head on. For a lot of physicians, especially those who were redeployed here from other departments, it was important just to have us ask if they were doing okay.”

Brian Schroeder, MHA, FACHE, FHM, assistant vice president for hospital and emergency medicine for Atrium Health, based in Charlotte, N.C., said one of the biggest sources of stress on his staff has been the constant pace of change – whether local hospital protocols, state policies, or guidelines from the Centers for Disease Control and Prevention. “The updating is difficult to keep up with. A lot of our physicians get worried and anxious that they’re not following the latest guidelines or correctly doing what they should be doing to care for COVID patients. One thing we’ve done to alleviate some of that fear and anxiety is through weekly huddles with our hospital teams, focusing on changes relevant to their work. We also have weekly ‘all-hands’ meetings for our 250 providers across 13 acute and four postacute facilities.”

Before COVID, it was difficult to get everyone together as one big group from hospitals up to 5 hours apart, but with the Microsoft Teams platform, they can all meet together.

“At the height of the pandemic, we’d convene weekly and share national statistics, organizational statistics, testing updates, changes to protocols,” Mr. Schroeder said. As the pace of change has slowed, these meetings were cut back to monthly. “Our physicians feel we are passing on information as soon as we get it. They know we’ll always tell them what we know.”

Sarah Richards, MD, assistant professor of internal medicine at the University of Nebraska, Omaha, who heads the Society of Hospital Medicine’s Well-Being Task Force, formed to address staff stress in the COVID environment, said there are things that health care systems can do to help mitigate job stress and burnout. But broader issues may need to be addressed at a national level. “SHM is trying to understand work-related stress – and to identify resources that could support doctors, so they can spend more of their time doing what they enjoy most, which is taking care of patients,” she said.

“We also recognize that people have had very different experiences, depending on geography, and at the individual level stressors are experienced very differently,” Dr. Richard noted. “One of the most common stressors we’ve heard from doctors is the challenge of caring for patients who are lonely and isolated in their hospital rooms, suffering and dying in new ways. In low-incidence areas, doctors are expressing guilt because they aren’t under as much stress as their colleagues. In high-incidence areas, doctors are already experiencing posttraumatic stress disorder.”

SHM’s Well-Being Task Force is working on a tool to help normalize these stressors and encourage open conversations about mental health issues. A guide called “HM COVID Check-in Guide for Self & Peers” is designed to help hospitalists break the culture of silence around well-being and burnout during COVID-19 and how people are handling and processing the pandemic experience. It is expected to be completed later this year, Dr. Richards said. Other SHM projects and resources for staff support are also in the works.
 

The impact on women doctors

In a recent Journal of Hospital Medicine article entitled “Collateral Damage: How COVID-19 is Adversely Impacting Women Physicians,” hospitalist Yemisi Jones, MD, medical director of continuing medical education at Cincinnati Children’s Hospital Medical Center, and colleagues argue that preexisting gender inequities in compensation, academic rank and leadership positions for physicians have made the COVID-19 crisis even more burdensome on female hospitalists.¹

“Increased childcare and schooling obligations, coupled with disproportionate household responsibilities and an inability to work from home, will likely result in female hospitalists struggling to meet family needs while pandemic-related work responsibilities are ramping up,” they write. COVID may intensify workplace inequalities, with a lack of recognition of the undue strain that group policies place on women.

“Often women suffer in silence,” said coauthor Jennifer O’Toole, MD, MEd, director of education in the division of hospital medicine at Cincinnati Children’s Hospital Medical Center and program director of the internal medicine–pediatrics residency. “We are not always the best self-advocates, although many of us are working on that.”

When women in hospital medicine take leadership roles, these often tend to involve mutual support activities, taking care of colleagues, and promoting collaborative work environments, Dr. Jones added. The stereotypical example is the committee that organizes celebrations when group members get married or have babies.

These activities can take a lot of time, she said. “We need to pay attention to that kind of role in our groups, because it’s important to the cohesiveness of the group. But it often goes unrecognized and doesn’t translate into the currency of promotion and leadership in medicine. When women go for promotions in the future, how will what happened during the COVID crisis impact their opportunities?”

What is the answer to overcoming these systemic inequities? Start with making sure women are part of the leadership team, with responsibilities for group policies, schedules, and other important decisions. “Look at your group’s leadership – particularly the higher positions. If it’s not diverse, ask why. ‘What is it about the structure of our group?’ Make a more concerted effort in your recruitment and retention,” Dr. Jones said.

The JHM article also recommends closely monitoring the direct and indirect effects of COVID-19 on female hospitalists, inquiring specifically about the needs of women in the organization, and ensuring that diversity, inclusion, and equity efforts are not suspended during the pandemic. Gender-based disparities in pay also need a closer look, and not just one time but reviewed periodically and adjusted accordingly.

Mentoring for early career women is important, but more so is sponsorship – someone in a high-level leadership role in the group sponsoring women who are rising up the career ladder, Dr. O’Toole said. “Professional women tend to be overmentored and undersponsored.”
 

What are the answers?

Ultimately, listening is key to try to help people get through the pandemic, Dr. Washburn said. “People become burned out when they feel leadership doesn’t understand their needs or doesn’t hear their concerns. Our group leaders all do clinical work, so they are seen as one of us. They try very hard; they have listening ears. But listening is just the first step. Next step is to work creatively to get the identified needs met.”

A few years ago, Johns Hopkins developed training in enhanced communication in health care for all hospital providers, including nurses and doctors, encouraging them to get trained in how to actively listen and address their patients’ emotional and social experiences as well as disease, Dr. Washburn explained. Learning how to listen better to patients can enhance skills at listening to colleagues, and vice versa. “We recognize the importance of better communication – for reducing sentinel events in the hospital and also for preventing staff burnout.”

Dr. Barnes also does physician coaching, and says a lot of that work is helping people achieve clarity on their core values. “Healing patients is a core identify for physicians; we want to take care of people. But other things can get in the way of that, and hospitalist groups can work at minimizing those barriers. We also need to learn, as hospitalists, that we work in a group. You need to be creative in how you do your team building, especially now, when you can no longer get together for dinner. Whatever it is, how do we bring our team back together? The biggest source of support for many hospitalists, beyond their family, is the group.”

Dr. Case said there is a longer-term need to study the root causes of burnout in hospitalists and to identify the issues that cause job stress. “What is modifiable? How can we tackle it? I see that as big part of my job every day. Being a physician is hard enough as it is. Let’s work to resolve those issues that add needlessly to the stress.”

“I think the pandemic brought a magnifying glass to how important a concern staff stress is,” Ms. Panek said. Resilience is important.

“We were working in our group on creating a culture that values trust and transparency, and then the COVID crisis hit,” she said. “But you can still keep working on those things. We would not have been as good or as positive as we were in managing this crisis without that preexisting culture to draw upon. We always said it was important. Now we know that’s true.”
 

Reference

1. Jones Y et al. Collateral Damage: How COVID-19 Is Adversely Impacting Women Physicians. J Hosp Med. 2020 August;15(8):507-9.

Clarissa Barnes, MD, a hospitalist at Avera McKennan Hospital in Sioux Falls, S.D., and until recently medical director of Avera’s LIGHT Program, a wellness-oriented service for doctors, nurse practitioners, and physician assistants, watched the COVID-19 crisis unfold up close in her community and her hospital. Sioux Falls traced its surge of COVID patients to an outbreak at a local meatpacking plant.

“In the beginning, we didn’t know much about the virus and its communicability, although we have since gotten a better handle on that,” she said. “We had questions: Should we give patients more fluids – or less? Steroids or not? In my experience as a hospitalist I never had patients die every day on my shift, but that was happening with COVID.” The crisis imposed serious stresses on frontline providers, and hospitalists were concerned about personal safety and exposure risk – not just for themselves but for their families.

“The first time I worked on the COVID unit, I moved into the guest room in our home, apart from my husband and our young children,” Dr. Barnes said. “Ultimately I caught the virus, although I have since recovered.” Her experience has highlighted how existing issues of job stress and burnout in hospital medicine have been exacerbated by COVID-19. Even physicians who consider themselves healthy may have little emotional reserve to draw upon in a crisis of this magnitude.

“We are social distancing at work, wearing masks, not eating together with our colleagues – with less camaraderie and social support than we used to have,” she said. “I feel exhausted and there’s no question that my colleagues and I have sacrificed a lot to deal with the pandemic.” Add to that the second front of the COVID-19 crisis, Dr. Barnes said, which is “fighting the medical information wars, trying to correct misinformation put out there by people. Physicians who have been on the front lines of the pandemic know how demoralizing it can be to have people negate your first-hand experience.”

The situation has gotten better in Sioux Falls, Dr. Barnes said, although cases have started rising in the state again. The stress, while not gone, is reduced. For some doctors, “COVID reminded us of why we do what we do. Some of the usual bureaucratic requirements were set aside and we could focus on what our patients needed and how to take care of them.”
 

Taking job stress seriously

Tiffani Panek, MA, SFHM, CLHM, administrator of the division of hospital medicine at Johns Hopkins Bayview Medical Center in Baltimore, said job stress is a major issue for hospitalist groups.

“We take it seriously here, and use a survey tool to measure morale in our group annually,” she said. “So far, knock on wood, Baltimore has not been one of the big hot spots, but we’ve definitely had waves of COVID patients.”

The Bayview hospitalist group has a diversified set of leaders, including a wellness director. “They’re always checking up on our people, keeping an eye on those who are most vulnerable. One of the stressors we hadn’t thought about before was for our people who live alone. With the isolation and lockdown, they haven’t been able to socialize, so we’ve made direct outreach, asking people how they were doing,” Ms. Panek said. “People know we’ve got their back – professionally and personally. They know, if there’s something we can do to help, we will do it.”

Bayview Medical Center has COVID-specific units and non-COVID units, and has tried to rotate hospitalist assignments because more than a couple days in a row spent wearing full personal protective equipment (PPE) is exhausting, Ms. Panek said. The group also allocated a respite room just outside the biocontainment unit, with a computer and opportunities for providers to just sit and take a breather – with appropriate social distancing. “It’s not fancy, but you just have to wear a mask, not full PPE.”

The Hopkins hospitalist group’s wellness director, Catherine Washburn, MD, also a working hospitalist, said providers are exhausted, and trying to transition to the new normal is a moving target.

“It’s hard for anyone to say what our lives will look like in 6 months,” she said. “People in our group have lost family members to COVID, or postponed major life events, like weddings. We acknowledge losses together as a group, and celebrate things worth celebrating, like babies or birthdays.”
 

Greatest COVID caseload

Joshua Case, MD, hospitalist medical director for 16 acute care hospitals of Northwell Health serving metropolitan New York City and Long Island, said his group’s hospitalists and other staff worked incredibly hard during the surge of COVID-19 patients in New York. “Northwell likely cared for more COVID patients than any other health care system in the U.S., if not the world.

“It’s vastly different now. We went from a peak of thousands of cases per day down to about 70-90 new cases a day across our system. We’re lucky our system recognized that COVID could be an issue early on, with all of the multifaceted stressors on patient care,” Dr. Case said. “We’ve done whatever we could to give people time off, especially as the census started to come down. We freed up as many supportive mental health services as we could, working with the health system’s employee assistance program.”

Northwell gave out numbers for the psychiatry department, with clinicians available 24/7 for a confidential call, along with outside volunteers and a network of trauma psychologists. “Our system also provided emergency child care for staff, including hospitalists, wherever we could, drawing upon community resources,” Dr. Case added.

“We recognize that we’re all in the same foxhole. That’s been a helpful attitude – recognizing that it’s okay to be upset in a crisis and to have trouble dealing with what’s going on,” he said. “We need to acknowledge that some of us are suffering and try to encourage people to face it head on. For a lot of physicians, especially those who were redeployed here from other departments, it was important just to have us ask if they were doing okay.”

Brian Schroeder, MHA, FACHE, FHM, assistant vice president for hospital and emergency medicine for Atrium Health, based in Charlotte, N.C., said one of the biggest sources of stress on his staff has been the constant pace of change – whether local hospital protocols, state policies, or guidelines from the Centers for Disease Control and Prevention. “The updating is difficult to keep up with. A lot of our physicians get worried and anxious that they’re not following the latest guidelines or correctly doing what they should be doing to care for COVID patients. One thing we’ve done to alleviate some of that fear and anxiety is through weekly huddles with our hospital teams, focusing on changes relevant to their work. We also have weekly ‘all-hands’ meetings for our 250 providers across 13 acute and four postacute facilities.”

Before COVID, it was difficult to get everyone together as one big group from hospitals up to 5 hours apart, but with the Microsoft Teams platform, they can all meet together.

“At the height of the pandemic, we’d convene weekly and share national statistics, organizational statistics, testing updates, changes to protocols,” Mr. Schroeder said. As the pace of change has slowed, these meetings were cut back to monthly. “Our physicians feel we are passing on information as soon as we get it. They know we’ll always tell them what we know.”

Sarah Richards, MD, assistant professor of internal medicine at the University of Nebraska, Omaha, who heads the Society of Hospital Medicine’s Well-Being Task Force, formed to address staff stress in the COVID environment, said there are things that health care systems can do to help mitigate job stress and burnout. But broader issues may need to be addressed at a national level. “SHM is trying to understand work-related stress – and to identify resources that could support doctors, so they can spend more of their time doing what they enjoy most, which is taking care of patients,” she said.

“We also recognize that people have had very different experiences, depending on geography, and at the individual level stressors are experienced very differently,” Dr. Richard noted. “One of the most common stressors we’ve heard from doctors is the challenge of caring for patients who are lonely and isolated in their hospital rooms, suffering and dying in new ways. In low-incidence areas, doctors are expressing guilt because they aren’t under as much stress as their colleagues. In high-incidence areas, doctors are already experiencing posttraumatic stress disorder.”

SHM’s Well-Being Task Force is working on a tool to help normalize these stressors and encourage open conversations about mental health issues. A guide called “HM COVID Check-in Guide for Self & Peers” is designed to help hospitalists break the culture of silence around well-being and burnout during COVID-19 and how people are handling and processing the pandemic experience. It is expected to be completed later this year, Dr. Richards said. Other SHM projects and resources for staff support are also in the works.
 

The impact on women doctors

In a recent Journal of Hospital Medicine article entitled “Collateral Damage: How COVID-19 is Adversely Impacting Women Physicians,” hospitalist Yemisi Jones, MD, medical director of continuing medical education at Cincinnati Children’s Hospital Medical Center, and colleagues argue that preexisting gender inequities in compensation, academic rank and leadership positions for physicians have made the COVID-19 crisis even more burdensome on female hospitalists.¹

“Increased childcare and schooling obligations, coupled with disproportionate household responsibilities and an inability to work from home, will likely result in female hospitalists struggling to meet family needs while pandemic-related work responsibilities are ramping up,” they write. COVID may intensify workplace inequalities, with a lack of recognition of the undue strain that group policies place on women.

“Often women suffer in silence,” said coauthor Jennifer O’Toole, MD, MEd, director of education in the division of hospital medicine at Cincinnati Children’s Hospital Medical Center and program director of the internal medicine–pediatrics residency. “We are not always the best self-advocates, although many of us are working on that.”

When women in hospital medicine take leadership roles, these often tend to involve mutual support activities, taking care of colleagues, and promoting collaborative work environments, Dr. Jones added. The stereotypical example is the committee that organizes celebrations when group members get married or have babies.

These activities can take a lot of time, she said. “We need to pay attention to that kind of role in our groups, because it’s important to the cohesiveness of the group. But it often goes unrecognized and doesn’t translate into the currency of promotion and leadership in medicine. When women go for promotions in the future, how will what happened during the COVID crisis impact their opportunities?”

What is the answer to overcoming these systemic inequities? Start with making sure women are part of the leadership team, with responsibilities for group policies, schedules, and other important decisions. “Look at your group’s leadership – particularly the higher positions. If it’s not diverse, ask why. ‘What is it about the structure of our group?’ Make a more concerted effort in your recruitment and retention,” Dr. Jones said.

The JHM article also recommends closely monitoring the direct and indirect effects of COVID-19 on female hospitalists, inquiring specifically about the needs of women in the organization, and ensuring that diversity, inclusion, and equity efforts are not suspended during the pandemic. Gender-based disparities in pay also need a closer look, and not just one time but reviewed periodically and adjusted accordingly.

Mentoring for early career women is important, but more so is sponsorship – someone in a high-level leadership role in the group sponsoring women who are rising up the career ladder, Dr. O’Toole said. “Professional women tend to be overmentored and undersponsored.”
 

What are the answers?

Ultimately, listening is key to try to help people get through the pandemic, Dr. Washburn said. “People become burned out when they feel leadership doesn’t understand their needs or doesn’t hear their concerns. Our group leaders all do clinical work, so they are seen as one of us. They try very hard; they have listening ears. But listening is just the first step. Next step is to work creatively to get the identified needs met.”

A few years ago, Johns Hopkins developed training in enhanced communication in health care for all hospital providers, including nurses and doctors, encouraging them to get trained in how to actively listen and address their patients’ emotional and social experiences as well as disease, Dr. Washburn explained. Learning how to listen better to patients can enhance skills at listening to colleagues, and vice versa. “We recognize the importance of better communication – for reducing sentinel events in the hospital and also for preventing staff burnout.”

Dr. Barnes also does physician coaching, and says a lot of that work is helping people achieve clarity on their core values. “Healing patients is a core identify for physicians; we want to take care of people. But other things can get in the way of that, and hospitalist groups can work at minimizing those barriers. We also need to learn, as hospitalists, that we work in a group. You need to be creative in how you do your team building, especially now, when you can no longer get together for dinner. Whatever it is, how do we bring our team back together? The biggest source of support for many hospitalists, beyond their family, is the group.”

Dr. Case said there is a longer-term need to study the root causes of burnout in hospitalists and to identify the issues that cause job stress. “What is modifiable? How can we tackle it? I see that as big part of my job every day. Being a physician is hard enough as it is. Let’s work to resolve those issues that add needlessly to the stress.”

“I think the pandemic brought a magnifying glass to how important a concern staff stress is,” Ms. Panek said. Resilience is important.

“We were working in our group on creating a culture that values trust and transparency, and then the COVID crisis hit,” she said. “But you can still keep working on those things. We would not have been as good or as positive as we were in managing this crisis without that preexisting culture to draw upon. We always said it was important. Now we know that’s true.”
 

Reference

1. Jones Y et al. Collateral Damage: How COVID-19 Is Adversely Impacting Women Physicians. J Hosp Med. 2020 August;15(8):507-9.

The first blood test to detect the presence of amyloid, a hallmark of Alzheimer’s disease, is now available for clinical use, according to C2N Diagnostics, the company behind the test’s development. The availability of the noninvasive, easily administered test is being called a milestone in the early detection and diagnosis of Alzheimer’s disease.

The blood test “introduces a new option for patients, families, and the medical community that have eagerly awaited innovative tools to address Alzheimer’s troubling problems,” Joel B. Braunstein, MD, MBA, CEO of C2N Diagnostics, said in a press release.

“This is really an important advance,” said Howard Fillit, MD, founding executive director and chief science officer of the Alzheimer’s Drug Discovery Foundation (ADDF), which partially funded the development of the test, in a separate press release.

“You can now walk into your doctor’s office to get a blood test to help detect Alzheimer’s disease,” said Dr. Fillit. “This test answers a critical need for less costly and accessible diagnostic testing in memory and dementia care.”
 

A word of caution

However, Maria C. Carrillo, PhD, chief science officer, Alzheimer’s Association, highlighted the need for caution. The test is “very new,” experts have only “limited information” about it, and it is only available by prescription from a healthcare provider for patients with cognitive impairment, said Dr. Carrillo.

“The test is not [Food and Drug Administration] approved and it does not, on its own, diagnose Alzheimer’s disease,” added Dr. Carrillo. “Without FDA review, healthcare providers lack the agency’s guidance for how to use it when making decisions about a person’s health or treatment.”

Dr. Carrillo also noted that the test has only been studied in a limited number of individuals and that few data are available regarding underrepresented populations.

“As a result, it is not clear how accurate or generalizable the results are for all individuals and populations,” she noted.

Another factor to consider, said Dr. Carrillo, is that the test is not covered by insurance, including Medicare and Medicaid.
 

How it works

The test (PrecivityAD) is for use in patients with cognitive impairment. It requires a very small blood sample – as little as a teaspoon – from the patient’s forearm. The physician sends the sample to C2N Diagnostic’s specialized laboratory, where it is analyzed using mass spectrometry to measure concentrations of amyloid beta 42 and 40 and to detect the presence of apolipoprotein E isoforms.

The lab report, which is sent to the patient’s physician, details biomarker levels and provides an overall combined score, known as the Amyloid Probability Score, to assess the likelihood of low, intermediate, or high levels of amyloid plaque in the brain.

The company reports that, on the basis of data from 686 patients older than 60 years who had subjective cognitive impairment or dementia, the test correctly identified brain amyloid plaque status, as determined by quantitative amyloid positron-emission tomography (PET) scans, in 86% of the patients. In the analysis, the area under the curve for the receiver operating characteristic was 0.88.

The company notes that the test, the results of which require interpretation by a health care provider, is an important new tool to aid physicians in the evaluation process.

The new blood test is currently available in 45 states, the District of Columbia, and Puerto Rico.

C2N Diagnostics is moving ahead with development of a brain health panel to detect multiple blood-based markers for Alzheimer’s disease to aid in disease staging, treatment monitoring, and differential diagnosis.

The ADDF believes the path to approval of treatments of Alzheimer’s disease starts with a better diagnosis, Dr. Fillit said in his organization’s press release.

“Investing in biomarker research has been a core goal for the ADDF because reliable, accessible, and affordable biomarkers for Alzheimer’s diagnosis are critical to our ability to find drugs to prevent, slow, and even cure the disease. Our funding helped bring the first PET scan to market and now has helped bring the first blood test to market,” he said.

In addition to the ADDF, the National Institutes of Health, the GHR Foundation, and the BrightFocus Foundation contributed funding for the development of the amyloid blood test.

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

The first blood test to detect the presence of amyloid, a hallmark of Alzheimer’s disease, is now available for clinical use, according to C2N Diagnostics, the company behind the test’s development. The availability of the noninvasive, easily administered test is being called a milestone in the early detection and diagnosis of Alzheimer’s disease.

The blood test “introduces a new option for patients, families, and the medical community that have eagerly awaited innovative tools to address Alzheimer’s troubling problems,” Joel B. Braunstein, MD, MBA, CEO of C2N Diagnostics, said in a press release.

“This is really an important advance,” said Howard Fillit, MD, founding executive director and chief science officer of the Alzheimer’s Drug Discovery Foundation (ADDF), which partially funded the development of the test, in a separate press release.

“You can now walk into your doctor’s office to get a blood test to help detect Alzheimer’s disease,” said Dr. Fillit. “This test answers a critical need for less costly and accessible diagnostic testing in memory and dementia care.”
 

A word of caution

However, Maria C. Carrillo, PhD, chief science officer, Alzheimer’s Association, highlighted the need for caution. The test is “very new,” experts have only “limited information” about it, and it is only available by prescription from a healthcare provider for patients with cognitive impairment, said Dr. Carrillo.

“The test is not [Food and Drug Administration] approved and it does not, on its own, diagnose Alzheimer’s disease,” added Dr. Carrillo. “Without FDA review, healthcare providers lack the agency’s guidance for how to use it when making decisions about a person’s health or treatment.”

Dr. Carrillo also noted that the test has only been studied in a limited number of individuals and that few data are available regarding underrepresented populations.

“As a result, it is not clear how accurate or generalizable the results are for all individuals and populations,” she noted.

Another factor to consider, said Dr. Carrillo, is that the test is not covered by insurance, including Medicare and Medicaid.
 

How it works

The test (PrecivityAD) is for use in patients with cognitive impairment. It requires a very small blood sample – as little as a teaspoon – from the patient’s forearm. The physician sends the sample to C2N Diagnostic’s specialized laboratory, where it is analyzed using mass spectrometry to measure concentrations of amyloid beta 42 and 40 and to detect the presence of apolipoprotein E isoforms.

The lab report, which is sent to the patient’s physician, details biomarker levels and provides an overall combined score, known as the Amyloid Probability Score, to assess the likelihood of low, intermediate, or high levels of amyloid plaque in the brain.

The company reports that, on the basis of data from 686 patients older than 60 years who had subjective cognitive impairment or dementia, the test correctly identified brain amyloid plaque status, as determined by quantitative amyloid positron-emission tomography (PET) scans, in 86% of the patients. In the analysis, the area under the curve for the receiver operating characteristic was 0.88.

The company notes that the test, the results of which require interpretation by a health care provider, is an important new tool to aid physicians in the evaluation process.

The new blood test is currently available in 45 states, the District of Columbia, and Puerto Rico.

C2N Diagnostics is moving ahead with development of a brain health panel to detect multiple blood-based markers for Alzheimer’s disease to aid in disease staging, treatment monitoring, and differential diagnosis.

The ADDF believes the path to approval of treatments of Alzheimer’s disease starts with a better diagnosis, Dr. Fillit said in his organization’s press release.

“Investing in biomarker research has been a core goal for the ADDF because reliable, accessible, and affordable biomarkers for Alzheimer’s diagnosis are critical to our ability to find drugs to prevent, slow, and even cure the disease. Our funding helped bring the first PET scan to market and now has helped bring the first blood test to market,” he said.

In addition to the ADDF, the National Institutes of Health, the GHR Foundation, and the BrightFocus Foundation contributed funding for the development of the amyloid blood test.

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

The first blood test to detect the presence of amyloid, a hallmark of Alzheimer’s disease, is now available for clinical use, according to C2N Diagnostics, the company behind the test’s development. The availability of the noninvasive, easily administered test is being called a milestone in the early detection and diagnosis of Alzheimer’s disease.

The blood test “introduces a new option for patients, families, and the medical community that have eagerly awaited innovative tools to address Alzheimer’s troubling problems,” Joel B. Braunstein, MD, MBA, CEO of C2N Diagnostics, said in a press release.

“This is really an important advance,” said Howard Fillit, MD, founding executive director and chief science officer of the Alzheimer’s Drug Discovery Foundation (ADDF), which partially funded the development of the test, in a separate press release.

“You can now walk into your doctor’s office to get a blood test to help detect Alzheimer’s disease,” said Dr. Fillit. “This test answers a critical need for less costly and accessible diagnostic testing in memory and dementia care.”
 

A word of caution

However, Maria C. Carrillo, PhD, chief science officer, Alzheimer’s Association, highlighted the need for caution. The test is “very new,” experts have only “limited information” about it, and it is only available by prescription from a healthcare provider for patients with cognitive impairment, said Dr. Carrillo.

“The test is not [Food and Drug Administration] approved and it does not, on its own, diagnose Alzheimer’s disease,” added Dr. Carrillo. “Without FDA review, healthcare providers lack the agency’s guidance for how to use it when making decisions about a person’s health or treatment.”

Dr. Carrillo also noted that the test has only been studied in a limited number of individuals and that few data are available regarding underrepresented populations.

“As a result, it is not clear how accurate or generalizable the results are for all individuals and populations,” she noted.

Another factor to consider, said Dr. Carrillo, is that the test is not covered by insurance, including Medicare and Medicaid.
 

How it works

The test (PrecivityAD) is for use in patients with cognitive impairment. It requires a very small blood sample – as little as a teaspoon – from the patient’s forearm. The physician sends the sample to C2N Diagnostic’s specialized laboratory, where it is analyzed using mass spectrometry to measure concentrations of amyloid beta 42 and 40 and to detect the presence of apolipoprotein E isoforms.

The lab report, which is sent to the patient’s physician, details biomarker levels and provides an overall combined score, known as the Amyloid Probability Score, to assess the likelihood of low, intermediate, or high levels of amyloid plaque in the brain.

The company reports that, on the basis of data from 686 patients older than 60 years who had subjective cognitive impairment or dementia, the test correctly identified brain amyloid plaque status, as determined by quantitative amyloid positron-emission tomography (PET) scans, in 86% of the patients. In the analysis, the area under the curve for the receiver operating characteristic was 0.88.

The company notes that the test, the results of which require interpretation by a health care provider, is an important new tool to aid physicians in the evaluation process.

The new blood test is currently available in 45 states, the District of Columbia, and Puerto Rico.

C2N Diagnostics is moving ahead with development of a brain health panel to detect multiple blood-based markers for Alzheimer’s disease to aid in disease staging, treatment monitoring, and differential diagnosis.

The ADDF believes the path to approval of treatments of Alzheimer’s disease starts with a better diagnosis, Dr. Fillit said in his organization’s press release.

“Investing in biomarker research has been a core goal for the ADDF because reliable, accessible, and affordable biomarkers for Alzheimer’s diagnosis are critical to our ability to find drugs to prevent, slow, and even cure the disease. Our funding helped bring the first PET scan to market and now has helped bring the first blood test to market,” he said.

In addition to the ADDF, the National Institutes of Health, the GHR Foundation, and the BrightFocus Foundation contributed funding for the development of the amyloid blood test.

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

Plagued by false starts, a few dashed hopes, but with perhaps a glimmer of light on the horizon, the race to find an effective treatment for COVID-19 continues. At last count, more than 300 treatments and 200 vaccines were in preclinical or clinical development (not to mention the numerous existing agents that are being evaluated for repurposing).

There is also a renewed interest in cannabinoid therapeutics — in particular, the nonpsychoactive agent cannabidiol (CBD) and the prospect of its modulating inflammatory and other disease-associated clinical indices, including SARS-CoV-2–induced viral load, hyperinflammation, the cytokine storm, and acute respiratory distress syndrome (ARDS).

Long hobbled by regulatory, political, and financial barriers, CBD’s potential ability to knock back COVID-19–related inflammation might just open doors that have been closed for years to CBD researchers.
 

Why CBD and why now?

CBD and the resulting therapeutics have been plagued by a complicated association with recreational cannabis use. It’s been just 2 years since CBD-based therapeutics moved into mainstream medicine — the US Food and Drug Administration (FDA) approved Epidiolex oral solution for the treatment of Lennox-Gastaut syndrome and Dravet syndrome, and in August, the FDA approved it for tuberous sclerosis complex.

CBD’s mechanism of action has not been fully elucidated, but on the basis of its role in immune responses — well described in research spanning more than two decades — it›s not surprising that cannabinoid researchers have thrown their hats into the COVID-19 drug development ring.

The anti-inflammatory potential of CBD is substantial and appears to be related to the fact that it shares 20 protein targets common to inflammation-related pathways, Jenny Wilkerson, PhD, research assistant professor at the University of Florida School of Pharmacy, Gainesville, Florida, explained to Medscape Medical News.

Among the various trials that are currently recruiting or are underway is one that is slated for completion this fall. CANDIDATE (Cannabidiol for COVID-19 Patients With Mild-to-Moderate COVID-19) is a randomized, controlled, double-blind study led by Brazilian researchers at the University of São Paulo. The study, which began recruitment this past August, enrolled 100 patients, 50 in the active treatment group (who received capsulated CBD 300 mg daily for 14 days plus pharmacologic therapy [antipyretics] and clinical measures) and 50 who received placebo.

The primary outcome is intended to help clarify the potential role of oral CBD for preventing COVID-19 disease progression, modifying disease-associated clinical indices, and modulating inflammatory parameters, such as the cytokine storm, according to lead investigator Jose Alexandre de Souza Crippa, MD, PhD, professor of neuropsychology at the Ribeirao Preto Medical School at the University of São Paulo in Brazil, in the description of the study on clinicaltrials.gov. Crippa declined to provide any additional information about the trial in an email to Medscape Medical News.
 

Calming or preventing the storm

While Crippa and colleagues wrap up their CBD trial in South America, several North American and Canadian researchers are seeking to clarify and address one of the most therapeutically challenging aspects of SARS-CoV-2 infection — the lung macrophage–orchestrated hyperinflammatory response.

Although hyperinflammation is not unique to SARS-CoV-2 infection, disease severity and COVID-19–related mortality have been linked to this rapid and prolonged surge of inflammatory cytokines (eg, interleukin 6 [IL-6], IL-10, tumor necrosis factors [TNF], and chemokines) and the cytokine storm.

“When you stimulate CB2 receptors (involved in fighting inflammation), you get a release of the same inflammatory cytokines that are involved in COVID,” Cecilia Costiniuk, MD, associate professor and researcher at the Research Institute of the McGill University Health Center, Montreal, Canada, told Medscape Medical News.

“So, if you can act on this receptor, you might be able to reduce the release of those damaging cytokines that are causing ARDS, lung damage, etc,” she explained. Targeting these inflammatory mediators has been a key strategy in research aimed at reducing COVID-19 severity and related mortality, which is where CBD comes into play.

“CBD is a very powerful immune regulator. It keeps the [immune] engine on, but it doesn’t push the gas pedal, and it doesn’t push the brake completely,” Babak Baban, PhD, professor and immunologist at the Dental College of Georgia at Augusta University, told Medscape Medical News.

To explore the effectiveness of CBD in reducing hyperactivated inflammatory reactions, Baban and colleagues examined the potential of CBD to ameliorate ARDS in a murine model. The group divided wild-type male mice into sham, control, and treatment groups.

The sham group received intranasal phosphate buffered saline; the treatment and control groups received a polyriboinosinic:polycytidylic acid (poly I:C) double-stranded RNA analogue (100 mcg daily for 3 days) to simulate the cytokine storm and clinical ARDS symptoms.

Following the second poly I:C dose, the treatment group received CBD 5 mg/kg intraperitoneally every other day for 6 days. The mice were sacrificed on day 8.

The study results, published in July in Cannabis and Cannabinoid Research, first confirmed that the poly I:C model simulated the cytokine storm in ARDS, reducing blood oxygen saturation by as much as 10% (from ±81.6% to ±72.2%).

Intraperitoneally administered CBD appeared to reverse these ARDS-like trends. “We observed a significant improvement in severe lymphopenia, a mild decline in the ratio of neutrophils to T cells, and significant reductions in levels of [inflammatory and immune factors] IL-6, IFN-gamma [interferon gamma], and in TNF-alpha after the second CBD dose,” Baban said.

There was also a marked downregulation in infiltrating neutrophils and macrophages in the lung, leading to partial restoration of lung morphology and structure. The investigators write that this suggests “a counter inflammatory role for CBD to limit ARDS progression.”

Additional findings from a follow-up study published in mid-October “provide strong data that CBD may partially assert its beneficial and protective impact through its regulation of the apelin peptide,” wrote Baban in an email to Medscape Medical News.

“Apelin may also be a reliable biomarker for early diagnosis of ARDS in general, and in COVID-19 in particular,” he wrote.

Questions remain concerning dose response and whether CBD alone or in combination with other phytocannabinoids is more effective for treating COVID-19. Timing is likewise unclear.

Baban explained that as a result of the biphasic nature of COVID-19, the “sweet spot” appears to be just before the innate immune response progresses into an inflammation-driven response and fibrotic lung damage occurs.

But Wilkerson isn’t as convinced. She said that as with a thermostat, the endocannabinoid system needs tweaking to get it in the right place, that is, to achieve immune homeostasis. The COVID cytokine storm is highly unpredictable, she added, saying, “Right now, the timing for controlling the COVID cytokine storm is really a moving target.”
 

Is safety a concern?

Safety questions are expected to arise, especially in relation to COVID-19. CBD is not risk free, and one size does not fit all. Human CBD studies report gastrointestinal and somnolent effects, as well as drug-drug interactions.

Findings from a recent systematic review of randomized, controlled CBD trials support overall tolerability, suggesting that serious adverse events are rare. Such events are believed to be related to drug-drug interactions rather than to CBD itself. On the flip side, it is nonintoxicating, and there does not appear to be potential for abuse.

“It’s generally well tolerated,” Wilkerson said. “There’ve now been several clinical trials in numerous patient population settings where basically the only time you really start to have issues is where you have patients on very select agents. But this is where a pharmacist would come into play.”

Costiniuk agreed: “Just because it’s cannabis, it doesn’t mean that there’s going to be strange or unusual effects; these people [ie, those with severe COVID-19] are in the hospital and monitored very closely.”
 

Delving into the weeds: What’s next?

Although non-COVID-19 cannabinoid researchers have encountered regulatory roadblocks, several research groups that have had the prescience to dive in at the right time are gaining momentum.

Baban’s team has connected with one of the nation’s few academic laboratories authorized to work with the SARS-CoV-2 virus and are awaiting protocol approval so that they can reproduce their research, this time using two CBD formulations (injectable and inhaled).

If findings are positive, they will move forward quickly to meet with the FDA, Baban said, adding that the team is also collaborating with two organizations to conduct human clinical trials in hopes of pushing up timing.

The initial article caught the eye of the World Health Organization, which included it in its global literature on the coronavirus resource section.

Israeli researchers have also been quite busy. InnoCan Pharma and Tel Aviv University are collaborating to explore the potential for CBD-loaded exosomes (minute extracellular particles that mediate intracellular communication, including via innate and adaptive immune responses). The group plans to use these loaded exosomes to target and facilitate recovery of COVID-19–damaged lung cells.

From a broader perspective, the prospects for harnessing cannabinoids for immune modulation will be more thoroughly explored in a special issue of Cannabis and Cannabinoid Research, which has extended its current call for papers, studies, abstracts, and conference proceedings until the end of December.

Like many of the therapeutic strategies under investigation for the treatment of COVID-19, studies in CBD may continue to raise more questions than answers.

Still, Wilkerson is optimistic. “Taken together, these studies along with countless others suggest that the complex pharmacophore of Cannabis sativa may hold therapeutic utility to treat lung inflammation, such as what is seen in a COVID-19 cytokine storm,» she told Medscape Medical News. “I’m very excited to see what comes out of the research.”

Baban, Wilkerson, and Costiniuk have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Plagued by false starts, a few dashed hopes, but with perhaps a glimmer of light on the horizon, the race to find an effective treatment for COVID-19 continues. At last count, more than 300 treatments and 200 vaccines were in preclinical or clinical development (not to mention the numerous existing agents that are being evaluated for repurposing).

There is also a renewed interest in cannabinoid therapeutics — in particular, the nonpsychoactive agent cannabidiol (CBD) and the prospect of its modulating inflammatory and other disease-associated clinical indices, including SARS-CoV-2–induced viral load, hyperinflammation, the cytokine storm, and acute respiratory distress syndrome (ARDS).

Long hobbled by regulatory, political, and financial barriers, CBD’s potential ability to knock back COVID-19–related inflammation might just open doors that have been closed for years to CBD researchers.
 

Why CBD and why now?

CBD and the resulting therapeutics have been plagued by a complicated association with recreational cannabis use. It’s been just 2 years since CBD-based therapeutics moved into mainstream medicine — the US Food and Drug Administration (FDA) approved Epidiolex oral solution for the treatment of Lennox-Gastaut syndrome and Dravet syndrome, and in August, the FDA approved it for tuberous sclerosis complex.

CBD’s mechanism of action has not been fully elucidated, but on the basis of its role in immune responses — well described in research spanning more than two decades — it›s not surprising that cannabinoid researchers have thrown their hats into the COVID-19 drug development ring.

The anti-inflammatory potential of CBD is substantial and appears to be related to the fact that it shares 20 protein targets common to inflammation-related pathways, Jenny Wilkerson, PhD, research assistant professor at the University of Florida School of Pharmacy, Gainesville, Florida, explained to Medscape Medical News.

Among the various trials that are currently recruiting or are underway is one that is slated for completion this fall. CANDIDATE (Cannabidiol for COVID-19 Patients With Mild-to-Moderate COVID-19) is a randomized, controlled, double-blind study led by Brazilian researchers at the University of São Paulo. The study, which began recruitment this past August, enrolled 100 patients, 50 in the active treatment group (who received capsulated CBD 300 mg daily for 14 days plus pharmacologic therapy [antipyretics] and clinical measures) and 50 who received placebo.

The primary outcome is intended to help clarify the potential role of oral CBD for preventing COVID-19 disease progression, modifying disease-associated clinical indices, and modulating inflammatory parameters, such as the cytokine storm, according to lead investigator Jose Alexandre de Souza Crippa, MD, PhD, professor of neuropsychology at the Ribeirao Preto Medical School at the University of São Paulo in Brazil, in the description of the study on clinicaltrials.gov. Crippa declined to provide any additional information about the trial in an email to Medscape Medical News.
 

Calming or preventing the storm

While Crippa and colleagues wrap up their CBD trial in South America, several North American and Canadian researchers are seeking to clarify and address one of the most therapeutically challenging aspects of SARS-CoV-2 infection — the lung macrophage–orchestrated hyperinflammatory response.

Although hyperinflammation is not unique to SARS-CoV-2 infection, disease severity and COVID-19–related mortality have been linked to this rapid and prolonged surge of inflammatory cytokines (eg, interleukin 6 [IL-6], IL-10, tumor necrosis factors [TNF], and chemokines) and the cytokine storm.

“When you stimulate CB2 receptors (involved in fighting inflammation), you get a release of the same inflammatory cytokines that are involved in COVID,” Cecilia Costiniuk, MD, associate professor and researcher at the Research Institute of the McGill University Health Center, Montreal, Canada, told Medscape Medical News.

“So, if you can act on this receptor, you might be able to reduce the release of those damaging cytokines that are causing ARDS, lung damage, etc,” she explained. Targeting these inflammatory mediators has been a key strategy in research aimed at reducing COVID-19 severity and related mortality, which is where CBD comes into play.

“CBD is a very powerful immune regulator. It keeps the [immune] engine on, but it doesn’t push the gas pedal, and it doesn’t push the brake completely,” Babak Baban, PhD, professor and immunologist at the Dental College of Georgia at Augusta University, told Medscape Medical News.

To explore the effectiveness of CBD in reducing hyperactivated inflammatory reactions, Baban and colleagues examined the potential of CBD to ameliorate ARDS in a murine model. The group divided wild-type male mice into sham, control, and treatment groups.

The sham group received intranasal phosphate buffered saline; the treatment and control groups received a polyriboinosinic:polycytidylic acid (poly I:C) double-stranded RNA analogue (100 mcg daily for 3 days) to simulate the cytokine storm and clinical ARDS symptoms.

Following the second poly I:C dose, the treatment group received CBD 5 mg/kg intraperitoneally every other day for 6 days. The mice were sacrificed on day 8.

The study results, published in July in Cannabis and Cannabinoid Research, first confirmed that the poly I:C model simulated the cytokine storm in ARDS, reducing blood oxygen saturation by as much as 10% (from ±81.6% to ±72.2%).

Intraperitoneally administered CBD appeared to reverse these ARDS-like trends. “We observed a significant improvement in severe lymphopenia, a mild decline in the ratio of neutrophils to T cells, and significant reductions in levels of [inflammatory and immune factors] IL-6, IFN-gamma [interferon gamma], and in TNF-alpha after the second CBD dose,” Baban said.

There was also a marked downregulation in infiltrating neutrophils and macrophages in the lung, leading to partial restoration of lung morphology and structure. The investigators write that this suggests “a counter inflammatory role for CBD to limit ARDS progression.”

Additional findings from a follow-up study published in mid-October “provide strong data that CBD may partially assert its beneficial and protective impact through its regulation of the apelin peptide,” wrote Baban in an email to Medscape Medical News.

“Apelin may also be a reliable biomarker for early diagnosis of ARDS in general, and in COVID-19 in particular,” he wrote.

Questions remain concerning dose response and whether CBD alone or in combination with other phytocannabinoids is more effective for treating COVID-19. Timing is likewise unclear.

Baban explained that as a result of the biphasic nature of COVID-19, the “sweet spot” appears to be just before the innate immune response progresses into an inflammation-driven response and fibrotic lung damage occurs.

But Wilkerson isn’t as convinced. She said that as with a thermostat, the endocannabinoid system needs tweaking to get it in the right place, that is, to achieve immune homeostasis. The COVID cytokine storm is highly unpredictable, she added, saying, “Right now, the timing for controlling the COVID cytokine storm is really a moving target.”
 

Is safety a concern?

Safety questions are expected to arise, especially in relation to COVID-19. CBD is not risk free, and one size does not fit all. Human CBD studies report gastrointestinal and somnolent effects, as well as drug-drug interactions.

Findings from a recent systematic review of randomized, controlled CBD trials support overall tolerability, suggesting that serious adverse events are rare. Such events are believed to be related to drug-drug interactions rather than to CBD itself. On the flip side, it is nonintoxicating, and there does not appear to be potential for abuse.

“It’s generally well tolerated,” Wilkerson said. “There’ve now been several clinical trials in numerous patient population settings where basically the only time you really start to have issues is where you have patients on very select agents. But this is where a pharmacist would come into play.”

Costiniuk agreed: “Just because it’s cannabis, it doesn’t mean that there’s going to be strange or unusual effects; these people [ie, those with severe COVID-19] are in the hospital and monitored very closely.”
 

Delving into the weeds: What’s next?

Although non-COVID-19 cannabinoid researchers have encountered regulatory roadblocks, several research groups that have had the prescience to dive in at the right time are gaining momentum.

Baban’s team has connected with one of the nation’s few academic laboratories authorized to work with the SARS-CoV-2 virus and are awaiting protocol approval so that they can reproduce their research, this time using two CBD formulations (injectable and inhaled).

If findings are positive, they will move forward quickly to meet with the FDA, Baban said, adding that the team is also collaborating with two organizations to conduct human clinical trials in hopes of pushing up timing.

The initial article caught the eye of the World Health Organization, which included it in its global literature on the coronavirus resource section.

Israeli researchers have also been quite busy. InnoCan Pharma and Tel Aviv University are collaborating to explore the potential for CBD-loaded exosomes (minute extracellular particles that mediate intracellular communication, including via innate and adaptive immune responses). The group plans to use these loaded exosomes to target and facilitate recovery of COVID-19–damaged lung cells.

From a broader perspective, the prospects for harnessing cannabinoids for immune modulation will be more thoroughly explored in a special issue of Cannabis and Cannabinoid Research, which has extended its current call for papers, studies, abstracts, and conference proceedings until the end of December.

Like many of the therapeutic strategies under investigation for the treatment of COVID-19, studies in CBD may continue to raise more questions than answers.

Still, Wilkerson is optimistic. “Taken together, these studies along with countless others suggest that the complex pharmacophore of Cannabis sativa may hold therapeutic utility to treat lung inflammation, such as what is seen in a COVID-19 cytokine storm,» she told Medscape Medical News. “I’m very excited to see what comes out of the research.”

Baban, Wilkerson, and Costiniuk have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Plagued by false starts, a few dashed hopes, but with perhaps a glimmer of light on the horizon, the race to find an effective treatment for COVID-19 continues. At last count, more than 300 treatments and 200 vaccines were in preclinical or clinical development (not to mention the numerous existing agents that are being evaluated for repurposing).

There is also a renewed interest in cannabinoid therapeutics — in particular, the nonpsychoactive agent cannabidiol (CBD) and the prospect of its modulating inflammatory and other disease-associated clinical indices, including SARS-CoV-2–induced viral load, hyperinflammation, the cytokine storm, and acute respiratory distress syndrome (ARDS).

Long hobbled by regulatory, political, and financial barriers, CBD’s potential ability to knock back COVID-19–related inflammation might just open doors that have been closed for years to CBD researchers.
 

Why CBD and why now?

CBD and the resulting therapeutics have been plagued by a complicated association with recreational cannabis use. It’s been just 2 years since CBD-based therapeutics moved into mainstream medicine — the US Food and Drug Administration (FDA) approved Epidiolex oral solution for the treatment of Lennox-Gastaut syndrome and Dravet syndrome, and in August, the FDA approved it for tuberous sclerosis complex.

CBD’s mechanism of action has not been fully elucidated, but on the basis of its role in immune responses — well described in research spanning more than two decades — it›s not surprising that cannabinoid researchers have thrown their hats into the COVID-19 drug development ring.

The anti-inflammatory potential of CBD is substantial and appears to be related to the fact that it shares 20 protein targets common to inflammation-related pathways, Jenny Wilkerson, PhD, research assistant professor at the University of Florida School of Pharmacy, Gainesville, Florida, explained to Medscape Medical News.

Among the various trials that are currently recruiting or are underway is one that is slated for completion this fall. CANDIDATE (Cannabidiol for COVID-19 Patients With Mild-to-Moderate COVID-19) is a randomized, controlled, double-blind study led by Brazilian researchers at the University of São Paulo. The study, which began recruitment this past August, enrolled 100 patients, 50 in the active treatment group (who received capsulated CBD 300 mg daily for 14 days plus pharmacologic therapy [antipyretics] and clinical measures) and 50 who received placebo.

The primary outcome is intended to help clarify the potential role of oral CBD for preventing COVID-19 disease progression, modifying disease-associated clinical indices, and modulating inflammatory parameters, such as the cytokine storm, according to lead investigator Jose Alexandre de Souza Crippa, MD, PhD, professor of neuropsychology at the Ribeirao Preto Medical School at the University of São Paulo in Brazil, in the description of the study on clinicaltrials.gov. Crippa declined to provide any additional information about the trial in an email to Medscape Medical News.
 

Calming or preventing the storm

While Crippa and colleagues wrap up their CBD trial in South America, several North American and Canadian researchers are seeking to clarify and address one of the most therapeutically challenging aspects of SARS-CoV-2 infection — the lung macrophage–orchestrated hyperinflammatory response.

Although hyperinflammation is not unique to SARS-CoV-2 infection, disease severity and COVID-19–related mortality have been linked to this rapid and prolonged surge of inflammatory cytokines (eg, interleukin 6 [IL-6], IL-10, tumor necrosis factors [TNF], and chemokines) and the cytokine storm.

“When you stimulate CB2 receptors (involved in fighting inflammation), you get a release of the same inflammatory cytokines that are involved in COVID,” Cecilia Costiniuk, MD, associate professor and researcher at the Research Institute of the McGill University Health Center, Montreal, Canada, told Medscape Medical News.

“So, if you can act on this receptor, you might be able to reduce the release of those damaging cytokines that are causing ARDS, lung damage, etc,” she explained. Targeting these inflammatory mediators has been a key strategy in research aimed at reducing COVID-19 severity and related mortality, which is where CBD comes into play.

“CBD is a very powerful immune regulator. It keeps the [immune] engine on, but it doesn’t push the gas pedal, and it doesn’t push the brake completely,” Babak Baban, PhD, professor and immunologist at the Dental College of Georgia at Augusta University, told Medscape Medical News.

To explore the effectiveness of CBD in reducing hyperactivated inflammatory reactions, Baban and colleagues examined the potential of CBD to ameliorate ARDS in a murine model. The group divided wild-type male mice into sham, control, and treatment groups.

The sham group received intranasal phosphate buffered saline; the treatment and control groups received a polyriboinosinic:polycytidylic acid (poly I:C) double-stranded RNA analogue (100 mcg daily for 3 days) to simulate the cytokine storm and clinical ARDS symptoms.

Following the second poly I:C dose, the treatment group received CBD 5 mg/kg intraperitoneally every other day for 6 days. The mice were sacrificed on day 8.

The study results, published in July in Cannabis and Cannabinoid Research, first confirmed that the poly I:C model simulated the cytokine storm in ARDS, reducing blood oxygen saturation by as much as 10% (from ±81.6% to ±72.2%).

Intraperitoneally administered CBD appeared to reverse these ARDS-like trends. “We observed a significant improvement in severe lymphopenia, a mild decline in the ratio of neutrophils to T cells, and significant reductions in levels of [inflammatory and immune factors] IL-6, IFN-gamma [interferon gamma], and in TNF-alpha after the second CBD dose,” Baban said.

There was also a marked downregulation in infiltrating neutrophils and macrophages in the lung, leading to partial restoration of lung morphology and structure. The investigators write that this suggests “a counter inflammatory role for CBD to limit ARDS progression.”

Additional findings from a follow-up study published in mid-October “provide strong data that CBD may partially assert its beneficial and protective impact through its regulation of the apelin peptide,” wrote Baban in an email to Medscape Medical News.

“Apelin may also be a reliable biomarker for early diagnosis of ARDS in general, and in COVID-19 in particular,” he wrote.

Questions remain concerning dose response and whether CBD alone or in combination with other phytocannabinoids is more effective for treating COVID-19. Timing is likewise unclear.

Baban explained that as a result of the biphasic nature of COVID-19, the “sweet spot” appears to be just before the innate immune response progresses into an inflammation-driven response and fibrotic lung damage occurs.

But Wilkerson isn’t as convinced. She said that as with a thermostat, the endocannabinoid system needs tweaking to get it in the right place, that is, to achieve immune homeostasis. The COVID cytokine storm is highly unpredictable, she added, saying, “Right now, the timing for controlling the COVID cytokine storm is really a moving target.”
 

Is safety a concern?

Safety questions are expected to arise, especially in relation to COVID-19. CBD is not risk free, and one size does not fit all. Human CBD studies report gastrointestinal and somnolent effects, as well as drug-drug interactions.

Findings from a recent systematic review of randomized, controlled CBD trials support overall tolerability, suggesting that serious adverse events are rare. Such events are believed to be related to drug-drug interactions rather than to CBD itself. On the flip side, it is nonintoxicating, and there does not appear to be potential for abuse.

“It’s generally well tolerated,” Wilkerson said. “There’ve now been several clinical trials in numerous patient population settings where basically the only time you really start to have issues is where you have patients on very select agents. But this is where a pharmacist would come into play.”

Costiniuk agreed: “Just because it’s cannabis, it doesn’t mean that there’s going to be strange or unusual effects; these people [ie, those with severe COVID-19] are in the hospital and monitored very closely.”
 

Delving into the weeds: What’s next?

Although non-COVID-19 cannabinoid researchers have encountered regulatory roadblocks, several research groups that have had the prescience to dive in at the right time are gaining momentum.

Baban’s team has connected with one of the nation’s few academic laboratories authorized to work with the SARS-CoV-2 virus and are awaiting protocol approval so that they can reproduce their research, this time using two CBD formulations (injectable and inhaled).

If findings are positive, they will move forward quickly to meet with the FDA, Baban said, adding that the team is also collaborating with two organizations to conduct human clinical trials in hopes of pushing up timing.

The initial article caught the eye of the World Health Organization, which included it in its global literature on the coronavirus resource section.

Israeli researchers have also been quite busy. InnoCan Pharma and Tel Aviv University are collaborating to explore the potential for CBD-loaded exosomes (minute extracellular particles that mediate intracellular communication, including via innate and adaptive immune responses). The group plans to use these loaded exosomes to target and facilitate recovery of COVID-19–damaged lung cells.

From a broader perspective, the prospects for harnessing cannabinoids for immune modulation will be more thoroughly explored in a special issue of Cannabis and Cannabinoid Research, which has extended its current call for papers, studies, abstracts, and conference proceedings until the end of December.

Like many of the therapeutic strategies under investigation for the treatment of COVID-19, studies in CBD may continue to raise more questions than answers.

Still, Wilkerson is optimistic. “Taken together, these studies along with countless others suggest that the complex pharmacophore of Cannabis sativa may hold therapeutic utility to treat lung inflammation, such as what is seen in a COVID-19 cytokine storm,» she told Medscape Medical News. “I’m very excited to see what comes out of the research.”

Baban, Wilkerson, and Costiniuk have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Apomorphine sublingual film (Kynmobi, Sunovion Pharmaceuticals) was efficacious and generally safe and well tolerated for the on-demand treatment of off episodes in Parkinson’s disease, long-term follow-up of a phase 3 study has shown. Besides the usual adverse effects with apomorphine, the sublingual film was associated with more oral adverse effects than seen with the injectable drug. However, it may have some advantages over subcutaneous apomorphine injections in terms of administration during off episodes.

The study was presented at the Movement Disorder Society 23rd International Congress of Parkinson’s Disease and Movement Disorders (Virtual) 2020.

For example, the new formulation is more convenient than carrying an injection. It comes in a small, tear-open packet that contains a medication strip patients place under their tongues.

“When a patient is in the off state, depending on how off they are, they could have a little difficulty opening the strip [packet], but anyone can open the strip for them,” said lead author Rajesh Pahwa, MD, professor of neurology and chief of the Parkinson and Movement Disorder Division at the University of Kansas Medical Center in Kansas City. “On the other hand with the subcutaneous, they have to give the injection themselves and a stranger or someone is not going to help them with that.”
 

Open-label safety and efficacy study

The aims of this open-label, 48-week follow-up were to add new patients to assess safety and tolerability over the long term and to see if continued benefit from a previous 12-week double-blind study was still present at 1 year for patients in the earlier study.

This multicenter study (NCT02542696) included “rollover” patients (n = 78 for safety; n = 70 for efficacy) from the previous phase 2/3 double-blind trial, as well as new patients with no prior exposure to apomorphine sublingual film (n = 347 for safety; n = 275 for efficacy).

New patients experienced one or more off episodes per day with a daily off time of 2 hours or more per day while on stable doses of levodopa/carbidopa. All had clinically meaningful responses to levodopa/carbidopa and were judged by the investigator to be Stage 1-3 by modified Hoehn and Yahr scale rating during ON periods.

Rollover patients completed the prior study and had no major changes in their anti-Parkinson’s medications since then. Mouth cankers or sores were exclusion criteria for either group. New subjects could not have received subcutaneous apomorphine within 7 days of a screening visit.

The demographics and baseline characteristics of the new and rollover groups were similar (approximately 64 years; 65%-71% male; 96% White; 8.3-9.6 years since diagnosis; 3.9 to 4.1 off episodes/day, and total mean daily levodopa dose of 1120 to 1478 mg).

Assessing only the group of new patients, the investigators reported that 80% had a Hoehn and Yahr score of 2 or 2.5 when in the ON state and a Movement Disorder Society–Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Part III predose score of 41.8.

At the beginning of this study, patients in an off period received titrated doses of 10-35 mg of sublingual apomorphine in 5 mg increments during sequential office visits until they achieved a tolerable full ON within 45 minutes of a dose. They then entered a 48-week safety and efficacy phase, during which they self-administered the drug at home up to five times daily for off episodes with a minimum of 2 hours between doses. The investigators could adjust the doses for safety or lack of efficacy.

Two-thirds of new patients and three-quarters of rollovers received doses in the 10-20 mg range. The highest dose in the study of 35 mg was used by only 8%-9% of patients, but the highest approved and marketed dose is 30 mg.
 

Long-term benefits

Onset of efficacy was achieved by 15 minutes after dose for both new and rollover patients, and maximal efficacy occurred by 30 minutes. Results were very similar at 24, 36, and 48 weeks. The investigators did not perform statistical analyses.

Across study weeks 1, 12, 24, 36, and 48, between 77% and 92% of new patients and between 65% and 77% of rollover patients self-reported full ON within 30 minutes. “The long-term benefits are maintained over a year as far as the speed of onset and the duration,” Dr. Pahwa said.

Treatment-emergent adverse events occurred in about half of the new and the rollover patient groups in the titration phase and in 71%-81% of patients during the long-term safety phase. Nearly all were mild to moderate in severity.

A large number of participants withdrew from this long-term safety phase because of adverse events – 90 (33%) of new enrollees and 16 (23%) of rollover patients. Only 4% dropped out for lack of efficacy, all in the new enrollee group. Because the sublingual formulation is delivered under the tongue, patients in that group had more oral side effects, Dr. Pahwa said. Otherwise, “the side effects were very similar to the subcutaneous delivery.”

Treatment-emergent adverse events specific to sublingual apomorphine included oral mucosal erythema, lip or tongue swelling, and mouth ulceration (6% to 7% of patients each). Occurring less often were glossodynia, oral candidiasis, stomatitis, and tongue ulceration (2% each).

These were in addition to adverse events typically occurring with subcutaneous apomorphine, which are nausea, falls, dizziness, somnolence, dyskinesia, syncope, and yawning.

There are no head-to-head comparisons of sublingual versus subcutaneous delivery of apomorphine. But based on experience, Dr. Pahwa said, “With the subcutaneous, you have a slightly faster onset of action compared to the sublingual. However, sublingual has a slightly longer duration of benefit.”

He predicted that patients may prefer using an injection for a faster benefit or a sublingual for a slightly longer benefit.
 

More therapeutic options are welcome

Commenting on the study, Ray Dorsey, MD, professor of neurology at the University of Rochester (N.Y.), said that, for people with more advanced Parkinson’s disease “there’s usually a caregiver who’s injecting someone with an off period, as opposed to sublingual, which seems like a much easier way of administering a drug, especially for people with motor fluctuations.”

He noted that adverse events that led to premature discontinuation from the study “are concerning about the overall tolerability of the drug, which also will be determined in clinical practice, and will likely influence its overall utility.”

However, more therapeutic options are welcome because “the number of people with advanced Parkinson’s disease is going to grow and grow substantially,” he said. “So having therapies that help people with more advanced Parkinson’s disease ... many of whom don’t reach the clinic ... are going to be increasingly important.”

The study was supported by Sunovion. Dr. Pahwa and Dr. Dorsey reported conflicts of interest with numerous sources in industry.
 

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

Apomorphine sublingual film (Kynmobi, Sunovion Pharmaceuticals) was efficacious and generally safe and well tolerated for the on-demand treatment of off episodes in Parkinson’s disease, long-term follow-up of a phase 3 study has shown. Besides the usual adverse effects with apomorphine, the sublingual film was associated with more oral adverse effects than seen with the injectable drug. However, it may have some advantages over subcutaneous apomorphine injections in terms of administration during off episodes.

The study was presented at the Movement Disorder Society 23rd International Congress of Parkinson’s Disease and Movement Disorders (Virtual) 2020.

For example, the new formulation is more convenient than carrying an injection. It comes in a small, tear-open packet that contains a medication strip patients place under their tongues.

“When a patient is in the off state, depending on how off they are, they could have a little difficulty opening the strip [packet], but anyone can open the strip for them,” said lead author Rajesh Pahwa, MD, professor of neurology and chief of the Parkinson and Movement Disorder Division at the University of Kansas Medical Center in Kansas City. “On the other hand with the subcutaneous, they have to give the injection themselves and a stranger or someone is not going to help them with that.”
 

Open-label safety and efficacy study

The aims of this open-label, 48-week follow-up were to add new patients to assess safety and tolerability over the long term and to see if continued benefit from a previous 12-week double-blind study was still present at 1 year for patients in the earlier study.

This multicenter study (NCT02542696) included “rollover” patients (n = 78 for safety; n = 70 for efficacy) from the previous phase 2/3 double-blind trial, as well as new patients with no prior exposure to apomorphine sublingual film (n = 347 for safety; n = 275 for efficacy).

New patients experienced one or more off episodes per day with a daily off time of 2 hours or more per day while on stable doses of levodopa/carbidopa. All had clinically meaningful responses to levodopa/carbidopa and were judged by the investigator to be Stage 1-3 by modified Hoehn and Yahr scale rating during ON periods.

Rollover patients completed the prior study and had no major changes in their anti-Parkinson’s medications since then. Mouth cankers or sores were exclusion criteria for either group. New subjects could not have received subcutaneous apomorphine within 7 days of a screening visit.

The demographics and baseline characteristics of the new and rollover groups were similar (approximately 64 years; 65%-71% male; 96% White; 8.3-9.6 years since diagnosis; 3.9 to 4.1 off episodes/day, and total mean daily levodopa dose of 1120 to 1478 mg).

Assessing only the group of new patients, the investigators reported that 80% had a Hoehn and Yahr score of 2 or 2.5 when in the ON state and a Movement Disorder Society–Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Part III predose score of 41.8.

At the beginning of this study, patients in an off period received titrated doses of 10-35 mg of sublingual apomorphine in 5 mg increments during sequential office visits until they achieved a tolerable full ON within 45 minutes of a dose. They then entered a 48-week safety and efficacy phase, during which they self-administered the drug at home up to five times daily for off episodes with a minimum of 2 hours between doses. The investigators could adjust the doses for safety or lack of efficacy.

Two-thirds of new patients and three-quarters of rollovers received doses in the 10-20 mg range. The highest dose in the study of 35 mg was used by only 8%-9% of patients, but the highest approved and marketed dose is 30 mg.
 

Long-term benefits

Onset of efficacy was achieved by 15 minutes after dose for both new and rollover patients, and maximal efficacy occurred by 30 minutes. Results were very similar at 24, 36, and 48 weeks. The investigators did not perform statistical analyses.

Across study weeks 1, 12, 24, 36, and 48, between 77% and 92% of new patients and between 65% and 77% of rollover patients self-reported full ON within 30 minutes. “The long-term benefits are maintained over a year as far as the speed of onset and the duration,” Dr. Pahwa said.

Treatment-emergent adverse events occurred in about half of the new and the rollover patient groups in the titration phase and in 71%-81% of patients during the long-term safety phase. Nearly all were mild to moderate in severity.

A large number of participants withdrew from this long-term safety phase because of adverse events – 90 (33%) of new enrollees and 16 (23%) of rollover patients. Only 4% dropped out for lack of efficacy, all in the new enrollee group. Because the sublingual formulation is delivered under the tongue, patients in that group had more oral side effects, Dr. Pahwa said. Otherwise, “the side effects were very similar to the subcutaneous delivery.”

Treatment-emergent adverse events specific to sublingual apomorphine included oral mucosal erythema, lip or tongue swelling, and mouth ulceration (6% to 7% of patients each). Occurring less often were glossodynia, oral candidiasis, stomatitis, and tongue ulceration (2% each).

These were in addition to adverse events typically occurring with subcutaneous apomorphine, which are nausea, falls, dizziness, somnolence, dyskinesia, syncope, and yawning.

There are no head-to-head comparisons of sublingual versus subcutaneous delivery of apomorphine. But based on experience, Dr. Pahwa said, “With the subcutaneous, you have a slightly faster onset of action compared to the sublingual. However, sublingual has a slightly longer duration of benefit.”

He predicted that patients may prefer using an injection for a faster benefit or a sublingual for a slightly longer benefit.
 

More therapeutic options are welcome

Commenting on the study, Ray Dorsey, MD, professor of neurology at the University of Rochester (N.Y.), said that, for people with more advanced Parkinson’s disease “there’s usually a caregiver who’s injecting someone with an off period, as opposed to sublingual, which seems like a much easier way of administering a drug, especially for people with motor fluctuations.”

He noted that adverse events that led to premature discontinuation from the study “are concerning about the overall tolerability of the drug, which also will be determined in clinical practice, and will likely influence its overall utility.”

However, more therapeutic options are welcome because “the number of people with advanced Parkinson’s disease is going to grow and grow substantially,” he said. “So having therapies that help people with more advanced Parkinson’s disease ... many of whom don’t reach the clinic ... are going to be increasingly important.”

The study was supported by Sunovion. Dr. Pahwa and Dr. Dorsey reported conflicts of interest with numerous sources in industry.
 

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

Apomorphine sublingual film (Kynmobi, Sunovion Pharmaceuticals) was efficacious and generally safe and well tolerated for the on-demand treatment of off episodes in Parkinson’s disease, long-term follow-up of a phase 3 study has shown. Besides the usual adverse effects with apomorphine, the sublingual film was associated with more oral adverse effects than seen with the injectable drug. However, it may have some advantages over subcutaneous apomorphine injections in terms of administration during off episodes.

The study was presented at the Movement Disorder Society 23rd International Congress of Parkinson’s Disease and Movement Disorders (Virtual) 2020.

For example, the new formulation is more convenient than carrying an injection. It comes in a small, tear-open packet that contains a medication strip patients place under their tongues.

“When a patient is in the off state, depending on how off they are, they could have a little difficulty opening the strip [packet], but anyone can open the strip for them,” said lead author Rajesh Pahwa, MD, professor of neurology and chief of the Parkinson and Movement Disorder Division at the University of Kansas Medical Center in Kansas City. “On the other hand with the subcutaneous, they have to give the injection themselves and a stranger or someone is not going to help them with that.”
 

Open-label safety and efficacy study

The aims of this open-label, 48-week follow-up were to add new patients to assess safety and tolerability over the long term and to see if continued benefit from a previous 12-week double-blind study was still present at 1 year for patients in the earlier study.

This multicenter study (NCT02542696) included “rollover” patients (n = 78 for safety; n = 70 for efficacy) from the previous phase 2/3 double-blind trial, as well as new patients with no prior exposure to apomorphine sublingual film (n = 347 for safety; n = 275 for efficacy).

New patients experienced one or more off episodes per day with a daily off time of 2 hours or more per day while on stable doses of levodopa/carbidopa. All had clinically meaningful responses to levodopa/carbidopa and were judged by the investigator to be Stage 1-3 by modified Hoehn and Yahr scale rating during ON periods.

Rollover patients completed the prior study and had no major changes in their anti-Parkinson’s medications since then. Mouth cankers or sores were exclusion criteria for either group. New subjects could not have received subcutaneous apomorphine within 7 days of a screening visit.

The demographics and baseline characteristics of the new and rollover groups were similar (approximately 64 years; 65%-71% male; 96% White; 8.3-9.6 years since diagnosis; 3.9 to 4.1 off episodes/day, and total mean daily levodopa dose of 1120 to 1478 mg).

Assessing only the group of new patients, the investigators reported that 80% had a Hoehn and Yahr score of 2 or 2.5 when in the ON state and a Movement Disorder Society–Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Part III predose score of 41.8.

At the beginning of this study, patients in an off period received titrated doses of 10-35 mg of sublingual apomorphine in 5 mg increments during sequential office visits until they achieved a tolerable full ON within 45 minutes of a dose. They then entered a 48-week safety and efficacy phase, during which they self-administered the drug at home up to five times daily for off episodes with a minimum of 2 hours between doses. The investigators could adjust the doses for safety or lack of efficacy.

Two-thirds of new patients and three-quarters of rollovers received doses in the 10-20 mg range. The highest dose in the study of 35 mg was used by only 8%-9% of patients, but the highest approved and marketed dose is 30 mg.
 

Long-term benefits

Onset of efficacy was achieved by 15 minutes after dose for both new and rollover patients, and maximal efficacy occurred by 30 minutes. Results were very similar at 24, 36, and 48 weeks. The investigators did not perform statistical analyses.

Across study weeks 1, 12, 24, 36, and 48, between 77% and 92% of new patients and between 65% and 77% of rollover patients self-reported full ON within 30 minutes. “The long-term benefits are maintained over a year as far as the speed of onset and the duration,” Dr. Pahwa said.

Treatment-emergent adverse events occurred in about half of the new and the rollover patient groups in the titration phase and in 71%-81% of patients during the long-term safety phase. Nearly all were mild to moderate in severity.

A large number of participants withdrew from this long-term safety phase because of adverse events – 90 (33%) of new enrollees and 16 (23%) of rollover patients. Only 4% dropped out for lack of efficacy, all in the new enrollee group. Because the sublingual formulation is delivered under the tongue, patients in that group had more oral side effects, Dr. Pahwa said. Otherwise, “the side effects were very similar to the subcutaneous delivery.”

Treatment-emergent adverse events specific to sublingual apomorphine included oral mucosal erythema, lip or tongue swelling, and mouth ulceration (6% to 7% of patients each). Occurring less often were glossodynia, oral candidiasis, stomatitis, and tongue ulceration (2% each).

These were in addition to adverse events typically occurring with subcutaneous apomorphine, which are nausea, falls, dizziness, somnolence, dyskinesia, syncope, and yawning.

There are no head-to-head comparisons of sublingual versus subcutaneous delivery of apomorphine. But based on experience, Dr. Pahwa said, “With the subcutaneous, you have a slightly faster onset of action compared to the sublingual. However, sublingual has a slightly longer duration of benefit.”

He predicted that patients may prefer using an injection for a faster benefit or a sublingual for a slightly longer benefit.
 

More therapeutic options are welcome

Commenting on the study, Ray Dorsey, MD, professor of neurology at the University of Rochester (N.Y.), said that, for people with more advanced Parkinson’s disease “there’s usually a caregiver who’s injecting someone with an off period, as opposed to sublingual, which seems like a much easier way of administering a drug, especially for people with motor fluctuations.”

He noted that adverse events that led to premature discontinuation from the study “are concerning about the overall tolerability of the drug, which also will be determined in clinical practice, and will likely influence its overall utility.”

However, more therapeutic options are welcome because “the number of people with advanced Parkinson’s disease is going to grow and grow substantially,” he said. “So having therapies that help people with more advanced Parkinson’s disease ... many of whom don’t reach the clinic ... are going to be increasingly important.”

The study was supported by Sunovion. Dr. Pahwa and Dr. Dorsey reported conflicts of interest with numerous sources in industry.
 

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

It may be possible to diagnose Parkinson’s disease with a skin test, a new study suggests. For the study, researchers used a chemical assay to detect clumping of the protein alpha-synuclein, a hallmark of Parkinson’s disease, in autopsy skin samples taken from patients who had Parkinson’s disease confirmed by brain pathology and from controls without the disease. The test showed a high degree of sensitivity and specificity for the diagnosis of Parkinson’s disease.

The study was published online in Movement Disorders.

“This test has a lot of promise,” said senior author Anumantha Kanthasamy, PhD, professor of biomedical sciences at Iowa State University in Ames. “At present there are no peripheral biomarkers for Parkinson’s disease. The current diagnosis is just based on symptoms, and the symptoms can be similar to many other neurological diseases,” he added. “It can take many years to establish a correct diagnosis and the accuracy is low even with experienced neurologists.”

If the current results can be replicated in samples from live patients and in those with very early stages of Parkinson’s disease, a skin test could allow early diagnosis and the possibility of starting preventive treatments to slow disease progression before symptoms develop too severely, the researchers suggest.
 

Sensitive and specific test

The blinded study used a seeding assay – used previously to detect misfolded proteins in prion diseases – to analyze 50 skin samples provided by the Arizona Study of Aging and Neurodegenerative Disorders/Brain and Body Donation Program based at Banner Sun Health Research Institute in Sun City.

Half of the skin samples came from patients with Parkinson’s disease and half came from people without neurologic disease. The protein assay correctly diagnosed 24 out of 25 patients with Parkinson’s disease and only one of the 25 controls had the protein clumping.

“At present, the only way to definitely diagnose Parkinson’s disease is on autopsy – by the detection of alpha-synuclein clumps [Lewy bodies] in the brain,” commented Charles Adler, MD, professor of neurology at Mayo Clinic Arizona in Scottsdale and a coinvestigator of the study. “In our research, we have also seen clumping of alpha-synuclein in many other organs including submandibular gland, colon, skin, heart, and stomach, but in terms of access, the skin is probably the easiest source.”

In this study, “we found this seeding assay for alpha-synuclein clumps to be extremely sensitive and specific in the diagnosis of Parkinson’s disease,” he added. “This is very valuable data as we have samples from patients with autopsy-validated Parkinson’s disease.”
 

A reliable biomarker?

The researchers are now starting a study in living patients with funding from the National Institutes of Health in which they will repeat the process comparing skin samples from patients with clinically diagnosed Parkinson’s disease and controls.

“We need to know whether analyzing alpha-synuclein clumping in skin biopsies from live patients with Parkinson’s disease would serve as a reliable biomarker for disease progression. Will clumping of this protein in skin samples increase over time and does it correspond with disease progression?” Dr. Adler said.

In future they are also hoping to test individuals who have not yet developed Parkinson’s disease but may have some prodromal type symptoms and to test whether this assay could measure a treatment effect of drug therapy.

Dr. Adler noted that they are currently conducting an autopsy study of skin samples from individuals who did not have clinical Parkinson’s disease when alive but in whom Lewy bodies have been found postmortem.

“This suggests that the disease pathology starts before Parkinson’s symptoms develop, and in the future, if we can diagnose Parkinson’s disease earlier then we may be able to stop progression,” he said.

“There is a long list of compounds that have been studied to try and slow progression but haven’t shown benefits, but by the time patients develop symptoms they already have significant disease and [have] lost most of their dopamine neurons,” he added. “If we could backtrack by 10 years, then these drugs may well make a difference.”

Dr. Adler also noted that currently more advanced patients may undergo invasive procedures such as deep brain stimulation or surgery. “It is of utmost importance that they have an accurate diagnosis before being subjected to such procedures.”

In addition, he pointed out that an accurate test would help the drug development process. “It is vitally important to enroll patients with an accurate diagnosis in clinical trials of new drugs. At present, a large percentage of patients in these trials may not actually have Parkinson’s disease, which makes it very difficult to show a treatment effect.”
 

Important step, but preliminary

Commenting on the research, James Beck, PhD, chief scientific officer of the Parkinson’s Foundation, said the study “is an important step toward the creation of a new way to potentially diagnose Parkinson’s disease.”

But he cautioned that this is a preliminary study. “To really confirm the possibility of using this approach for diagnosing Parkinson’s disease, a larger study will be necessary. And it will be important to test this in a population with early disease – the most difficult group to accurately diagnose.”

Also commenting on the findings, Beate Ritz, MD, PhD, an epidemiologist at UCLA Fielding School of Public Health in Los Angeles, who is part of a team also working on ways to measure abnormal alpha-synuclein to diagnose Parkinson’s disease, described the current study of skin samples as “pretty nifty.”

“Their research shows clearly that they can distinguish between patients with Parkinson’s disease and controls in this way,” she said. “The big advantage of this study is that they have brain pathology, so they know exactly which individuals had Parkinson’s disease.”

Dr. Ritz is working with Gal Bitan, PhD, from the UCLA Brain Research Institute on a potential blood test to measure abnormal alpha-synuclein.

Dr. Ritz explained that it is not possible to measure alpha-synuclein pathology in regular blood samples as it is expressed normally in red blood cells, but they are measuring the protein and its more toxic phosphorylated form from exosomes, which contain the waste discarded by cells using technology that determines the origin of these exosomes.

“Alpha-synuclein itself is not a problem. It is the way it misfolds that causes toxicity and disrupts the workings of the cell,” Dr. Ritz added. “In Parkinson’s disease, it is particularly toxic to dopaminergic neurons, and in multiple system atrophy, it is toxic to glial cells, so if we can identify the source of the protein then that could be helpful.”

The study was funded by the National Institutes of Health and the US Army Medical Research Materiel Command. The study authors, Dr. Beck, and Dr. Ritz have disclosed no relevant financial relationships.
 

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

It may be possible to diagnose Parkinson’s disease with a skin test, a new study suggests. For the study, researchers used a chemical assay to detect clumping of the protein alpha-synuclein, a hallmark of Parkinson’s disease, in autopsy skin samples taken from patients who had Parkinson’s disease confirmed by brain pathology and from controls without the disease. The test showed a high degree of sensitivity and specificity for the diagnosis of Parkinson’s disease.

The study was published online in Movement Disorders.

“This test has a lot of promise,” said senior author Anumantha Kanthasamy, PhD, professor of biomedical sciences at Iowa State University in Ames. “At present there are no peripheral biomarkers for Parkinson’s disease. The current diagnosis is just based on symptoms, and the symptoms can be similar to many other neurological diseases,” he added. “It can take many years to establish a correct diagnosis and the accuracy is low even with experienced neurologists.”

If the current results can be replicated in samples from live patients and in those with very early stages of Parkinson’s disease, a skin test could allow early diagnosis and the possibility of starting preventive treatments to slow disease progression before symptoms develop too severely, the researchers suggest.
 

Sensitive and specific test

The blinded study used a seeding assay – used previously to detect misfolded proteins in prion diseases – to analyze 50 skin samples provided by the Arizona Study of Aging and Neurodegenerative Disorders/Brain and Body Donation Program based at Banner Sun Health Research Institute in Sun City.

Half of the skin samples came from patients with Parkinson’s disease and half came from people without neurologic disease. The protein assay correctly diagnosed 24 out of 25 patients with Parkinson’s disease and only one of the 25 controls had the protein clumping.

“At present, the only way to definitely diagnose Parkinson’s disease is on autopsy – by the detection of alpha-synuclein clumps [Lewy bodies] in the brain,” commented Charles Adler, MD, professor of neurology at Mayo Clinic Arizona in Scottsdale and a coinvestigator of the study. “In our research, we have also seen clumping of alpha-synuclein in many other organs including submandibular gland, colon, skin, heart, and stomach, but in terms of access, the skin is probably the easiest source.”

In this study, “we found this seeding assay for alpha-synuclein clumps to be extremely sensitive and specific in the diagnosis of Parkinson’s disease,” he added. “This is very valuable data as we have samples from patients with autopsy-validated Parkinson’s disease.”
 

A reliable biomarker?

The researchers are now starting a study in living patients with funding from the National Institutes of Health in which they will repeat the process comparing skin samples from patients with clinically diagnosed Parkinson’s disease and controls.

“We need to know whether analyzing alpha-synuclein clumping in skin biopsies from live patients with Parkinson’s disease would serve as a reliable biomarker for disease progression. Will clumping of this protein in skin samples increase over time and does it correspond with disease progression?” Dr. Adler said.

In future they are also hoping to test individuals who have not yet developed Parkinson’s disease but may have some prodromal type symptoms and to test whether this assay could measure a treatment effect of drug therapy.

Dr. Adler noted that they are currently conducting an autopsy study of skin samples from individuals who did not have clinical Parkinson’s disease when alive but in whom Lewy bodies have been found postmortem.

“This suggests that the disease pathology starts before Parkinson’s symptoms develop, and in the future, if we can diagnose Parkinson’s disease earlier then we may be able to stop progression,” he said.

“There is a long list of compounds that have been studied to try and slow progression but haven’t shown benefits, but by the time patients develop symptoms they already have significant disease and [have] lost most of their dopamine neurons,” he added. “If we could backtrack by 10 years, then these drugs may well make a difference.”

Dr. Adler also noted that currently more advanced patients may undergo invasive procedures such as deep brain stimulation or surgery. “It is of utmost importance that they have an accurate diagnosis before being subjected to such procedures.”

In addition, he pointed out that an accurate test would help the drug development process. “It is vitally important to enroll patients with an accurate diagnosis in clinical trials of new drugs. At present, a large percentage of patients in these trials may not actually have Parkinson’s disease, which makes it very difficult to show a treatment effect.”
 

Important step, but preliminary

Commenting on the research, James Beck, PhD, chief scientific officer of the Parkinson’s Foundation, said the study “is an important step toward the creation of a new way to potentially diagnose Parkinson’s disease.”

But he cautioned that this is a preliminary study. “To really confirm the possibility of using this approach for diagnosing Parkinson’s disease, a larger study will be necessary. And it will be important to test this in a population with early disease – the most difficult group to accurately diagnose.”

Also commenting on the findings, Beate Ritz, MD, PhD, an epidemiologist at UCLA Fielding School of Public Health in Los Angeles, who is part of a team also working on ways to measure abnormal alpha-synuclein to diagnose Parkinson’s disease, described the current study of skin samples as “pretty nifty.”

“Their research shows clearly that they can distinguish between patients with Parkinson’s disease and controls in this way,” she said. “The big advantage of this study is that they have brain pathology, so they know exactly which individuals had Parkinson’s disease.”

Dr. Ritz is working with Gal Bitan, PhD, from the UCLA Brain Research Institute on a potential blood test to measure abnormal alpha-synuclein.

Dr. Ritz explained that it is not possible to measure alpha-synuclein pathology in regular blood samples as it is expressed normally in red blood cells, but they are measuring the protein and its more toxic phosphorylated form from exosomes, which contain the waste discarded by cells using technology that determines the origin of these exosomes.

“Alpha-synuclein itself is not a problem. It is the way it misfolds that causes toxicity and disrupts the workings of the cell,” Dr. Ritz added. “In Parkinson’s disease, it is particularly toxic to dopaminergic neurons, and in multiple system atrophy, it is toxic to glial cells, so if we can identify the source of the protein then that could be helpful.”

The study was funded by the National Institutes of Health and the US Army Medical Research Materiel Command. The study authors, Dr. Beck, and Dr. Ritz have disclosed no relevant financial relationships.
 

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

It may be possible to diagnose Parkinson’s disease with a skin test, a new study suggests. For the study, researchers used a chemical assay to detect clumping of the protein alpha-synuclein, a hallmark of Parkinson’s disease, in autopsy skin samples taken from patients who had Parkinson’s disease confirmed by brain pathology and from controls without the disease. The test showed a high degree of sensitivity and specificity for the diagnosis of Parkinson’s disease.

The study was published online in Movement Disorders.

“This test has a lot of promise,” said senior author Anumantha Kanthasamy, PhD, professor of biomedical sciences at Iowa State University in Ames. “At present there are no peripheral biomarkers for Parkinson’s disease. The current diagnosis is just based on symptoms, and the symptoms can be similar to many other neurological diseases,” he added. “It can take many years to establish a correct diagnosis and the accuracy is low even with experienced neurologists.”

If the current results can be replicated in samples from live patients and in those with very early stages of Parkinson’s disease, a skin test could allow early diagnosis and the possibility of starting preventive treatments to slow disease progression before symptoms develop too severely, the researchers suggest.
 

Sensitive and specific test

The blinded study used a seeding assay – used previously to detect misfolded proteins in prion diseases – to analyze 50 skin samples provided by the Arizona Study of Aging and Neurodegenerative Disorders/Brain and Body Donation Program based at Banner Sun Health Research Institute in Sun City.

Half of the skin samples came from patients with Parkinson’s disease and half came from people without neurologic disease. The protein assay correctly diagnosed 24 out of 25 patients with Parkinson’s disease and only one of the 25 controls had the protein clumping.

“At present, the only way to definitely diagnose Parkinson’s disease is on autopsy – by the detection of alpha-synuclein clumps [Lewy bodies] in the brain,” commented Charles Adler, MD, professor of neurology at Mayo Clinic Arizona in Scottsdale and a coinvestigator of the study. “In our research, we have also seen clumping of alpha-synuclein in many other organs including submandibular gland, colon, skin, heart, and stomach, but in terms of access, the skin is probably the easiest source.”

In this study, “we found this seeding assay for alpha-synuclein clumps to be extremely sensitive and specific in the diagnosis of Parkinson’s disease,” he added. “This is very valuable data as we have samples from patients with autopsy-validated Parkinson’s disease.”
 

A reliable biomarker?

The researchers are now starting a study in living patients with funding from the National Institutes of Health in which they will repeat the process comparing skin samples from patients with clinically diagnosed Parkinson’s disease and controls.

“We need to know whether analyzing alpha-synuclein clumping in skin biopsies from live patients with Parkinson’s disease would serve as a reliable biomarker for disease progression. Will clumping of this protein in skin samples increase over time and does it correspond with disease progression?” Dr. Adler said.

In future they are also hoping to test individuals who have not yet developed Parkinson’s disease but may have some prodromal type symptoms and to test whether this assay could measure a treatment effect of drug therapy.

Dr. Adler noted that they are currently conducting an autopsy study of skin samples from individuals who did not have clinical Parkinson’s disease when alive but in whom Lewy bodies have been found postmortem.

“This suggests that the disease pathology starts before Parkinson’s symptoms develop, and in the future, if we can diagnose Parkinson’s disease earlier then we may be able to stop progression,” he said.

“There is a long list of compounds that have been studied to try and slow progression but haven’t shown benefits, but by the time patients develop symptoms they already have significant disease and [have] lost most of their dopamine neurons,” he added. “If we could backtrack by 10 years, then these drugs may well make a difference.”

Dr. Adler also noted that currently more advanced patients may undergo invasive procedures such as deep brain stimulation or surgery. “It is of utmost importance that they have an accurate diagnosis before being subjected to such procedures.”

In addition, he pointed out that an accurate test would help the drug development process. “It is vitally important to enroll patients with an accurate diagnosis in clinical trials of new drugs. At present, a large percentage of patients in these trials may not actually have Parkinson’s disease, which makes it very difficult to show a treatment effect.”
 

Important step, but preliminary

Commenting on the research, James Beck, PhD, chief scientific officer of the Parkinson’s Foundation, said the study “is an important step toward the creation of a new way to potentially diagnose Parkinson’s disease.”

But he cautioned that this is a preliminary study. “To really confirm the possibility of using this approach for diagnosing Parkinson’s disease, a larger study will be necessary. And it will be important to test this in a population with early disease – the most difficult group to accurately diagnose.”

Also commenting on the findings, Beate Ritz, MD, PhD, an epidemiologist at UCLA Fielding School of Public Health in Los Angeles, who is part of a team also working on ways to measure abnormal alpha-synuclein to diagnose Parkinson’s disease, described the current study of skin samples as “pretty nifty.”

“Their research shows clearly that they can distinguish between patients with Parkinson’s disease and controls in this way,” she said. “The big advantage of this study is that they have brain pathology, so they know exactly which individuals had Parkinson’s disease.”

Dr. Ritz is working with Gal Bitan, PhD, from the UCLA Brain Research Institute on a potential blood test to measure abnormal alpha-synuclein.

Dr. Ritz explained that it is not possible to measure alpha-synuclein pathology in regular blood samples as it is expressed normally in red blood cells, but they are measuring the protein and its more toxic phosphorylated form from exosomes, which contain the waste discarded by cells using technology that determines the origin of these exosomes.

“Alpha-synuclein itself is not a problem. It is the way it misfolds that causes toxicity and disrupts the workings of the cell,” Dr. Ritz added. “In Parkinson’s disease, it is particularly toxic to dopaminergic neurons, and in multiple system atrophy, it is toxic to glial cells, so if we can identify the source of the protein then that could be helpful.”

The study was funded by the National Institutes of Health and the US Army Medical Research Materiel Command. The study authors, Dr. Beck, and Dr. Ritz have disclosed no relevant financial relationships.
 

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

Last month, the American College of Rheumatology joined with 11 other medical associations and disease societies asking health insurance giant UnitedHealthcare (UHC) to not proceed with its proposed copay accumulator medical benefit program.

Copay accumulators are policies adopted by insurance companies or their pharmacy benefit managers to exclude patient copayment assistance programs for high-cost drugs, which are promulgated by the drug manufacturers, from being applied to a patient’s annual deductibles or out-of-pocket maximums. The manufacturer’s copay assistance, such as in the form of coupons, is designed to minimize the patient’s out-of-pocket costs. But insurers believe manufacturers will have no pressure to lower the prices of expensive specialty drugs unless patients are unable to afford them. Copay accumulators thus are aimed at giving insurers more leverage in negotiating prices for high-cost drugs.

UHC issued its new copay accumulator protocol for commercial individual and fully insured group plans in early October, effective Jan. 1, 2021, “in order to align employer costs for specialty medications with actual member out of pocket and deductibles,” according to the company’s announcement. In other words, patients will need to pay a higher share of the costs of these medications, said rheumatologist Christopher Phillips, MD, who chairs the Insurance Subcommittee of ACR’s Rheumatologic Care Committee. The annual price of biologic therapies for rheumatologic conditions ranges from $22,000 to $44,000, according to a recent press release from ACR.

The copay accumulator will negate the benefits of manufacturers’ copayment assistance programs for the patient, shifting more of the cost to the patient. With patients being forced to pay a higher share of drug costs for expensive biologic treatments for rheumatoid arthritis, lupus, and other rheumatologic conditions, they’ll stop taking the treatments, Dr. Phillips said.

“In my solo rheumatology practice in Paducah, Kentucky, when I’ve seen this kind of program applied on the pharmacy benefit side, rather than the medical benefit side, almost uniformly patients stop taking the high-cost treatments.” That can lead to disease flares, complications, and permanent disability. The newer rheumatologic drugs can cost $500 to $1,000 per treatment, and in many cases, there’s no generic or lower-cost alternative, he says. “We see policies like this as sacrificing patients to the battle over high drug prices. It’s bad practice, bad for patient outcomes, and nobody – apart from the payer – benefits.”

In ACR’s 2020 Rheumatic Disease Patient Survey, nearly half of 1,109 online survey respondents who had rheumatic diseases reported out-of-pocket costs greater than $1,000 per year for treatment. An IQVIA report from 2016 found that one in four specialty brand prescriptions are abandoned during the deductible phase, three times the rate seen when there is no deductible.

In an Oct. 7 letter to UHC, the 12 groups acknowledged that the drugs targeted by the accumulator policy are expensive. “However, they are also vitally important for our patients.” In addition to the ACR, the organizations involved include the AIDS Institute, American Academy of Dermatology Association, American Academy of Neurology, American College of Gastroenterology, American Gastroenterological Association, American Kidney Fund, Arthritis Foundation, Association for Clinical Oncology, Cancer Support Community, Coalition of State Rheumatology Organizations, and National Multiple Sclerosis Society.

UHC did not reply to questions in time for publication.


 

First large-scale payer to try copay accumulator program

Under UHC’s proposed policy, providers will be required to use UHC’s portal to report payment information received from drug manufacturer copay assistance programs that are applied to patients’ cost share of these drugs through a complex, 14-step “coupon submission process” involving multiple technology interfaces. “My first oath as a physician is to do no harm to my patient. Many of us are concerned about making these reports, which could harm our patients and undermine the doctor-patient relationship,” Dr. Phillips said.

“If I don’t report, what happens? I don’t think we know the answer to that. Some of us may decide we need to part ways with UHC.” Others may decline to participate in the drug manufacturers’ coupon programs beyond simply informing patients that manufacturer assistance is available.

“We’ve watched these copay accumulator policies for several years,” he said. “Some of them are rather opaque, with names like ‘copay savings programs’ or ‘copay value programs.’ But we had not seen a large-scale payer try to do this until now. Let’s face it: If UHC’s policy goes through, you can count the days until we see it from others.”

The Department of Health & Human Services, in its May 2020 final federal “Notice of Benefit and Payment Parameters for 2021,” indicated that individual states have the responsibility to regulate copay accumulator programs. Five states have banned them or restricted their use for individual and small group health plans. Arizona, Illinois, Virginia, and West Virginia passed such laws in 2019, and Georgia did so earlier this year.

“In next year’s state legislative sessions, we’ll make it a priority to pursue similar laws in other states,” Dr. Phillips said. “I’d encourage rheumatologists to educate their patients on the issues and be active in advocating for them.”

Last month, the American College of Rheumatology joined with 11 other medical associations and disease societies asking health insurance giant UnitedHealthcare (UHC) to not proceed with its proposed copay accumulator medical benefit program.

Copay accumulators are policies adopted by insurance companies or their pharmacy benefit managers to exclude patient copayment assistance programs for high-cost drugs, which are promulgated by the drug manufacturers, from being applied to a patient’s annual deductibles or out-of-pocket maximums. The manufacturer’s copay assistance, such as in the form of coupons, is designed to minimize the patient’s out-of-pocket costs. But insurers believe manufacturers will have no pressure to lower the prices of expensive specialty drugs unless patients are unable to afford them. Copay accumulators thus are aimed at giving insurers more leverage in negotiating prices for high-cost drugs.

UHC issued its new copay accumulator protocol for commercial individual and fully insured group plans in early October, effective Jan. 1, 2021, “in order to align employer costs for specialty medications with actual member out of pocket and deductibles,” according to the company’s announcement. In other words, patients will need to pay a higher share of the costs of these medications, said rheumatologist Christopher Phillips, MD, who chairs the Insurance Subcommittee of ACR’s Rheumatologic Care Committee. The annual price of biologic therapies for rheumatologic conditions ranges from $22,000 to $44,000, according to a recent press release from ACR.

The copay accumulator will negate the benefits of manufacturers’ copayment assistance programs for the patient, shifting more of the cost to the patient. With patients being forced to pay a higher share of drug costs for expensive biologic treatments for rheumatoid arthritis, lupus, and other rheumatologic conditions, they’ll stop taking the treatments, Dr. Phillips said.

“In my solo rheumatology practice in Paducah, Kentucky, when I’ve seen this kind of program applied on the pharmacy benefit side, rather than the medical benefit side, almost uniformly patients stop taking the high-cost treatments.” That can lead to disease flares, complications, and permanent disability. The newer rheumatologic drugs can cost $500 to $1,000 per treatment, and in many cases, there’s no generic or lower-cost alternative, he says. “We see policies like this as sacrificing patients to the battle over high drug prices. It’s bad practice, bad for patient outcomes, and nobody – apart from the payer – benefits.”

In ACR’s 2020 Rheumatic Disease Patient Survey, nearly half of 1,109 online survey respondents who had rheumatic diseases reported out-of-pocket costs greater than $1,000 per year for treatment. An IQVIA report from 2016 found that one in four specialty brand prescriptions are abandoned during the deductible phase, three times the rate seen when there is no deductible.

In an Oct. 7 letter to UHC, the 12 groups acknowledged that the drugs targeted by the accumulator policy are expensive. “However, they are also vitally important for our patients.” In addition to the ACR, the organizations involved include the AIDS Institute, American Academy of Dermatology Association, American Academy of Neurology, American College of Gastroenterology, American Gastroenterological Association, American Kidney Fund, Arthritis Foundation, Association for Clinical Oncology, Cancer Support Community, Coalition of State Rheumatology Organizations, and National Multiple Sclerosis Society.

UHC did not reply to questions in time for publication.


 

First large-scale payer to try copay accumulator program

Under UHC’s proposed policy, providers will be required to use UHC’s portal to report payment information received from drug manufacturer copay assistance programs that are applied to patients’ cost share of these drugs through a complex, 14-step “coupon submission process” involving multiple technology interfaces. “My first oath as a physician is to do no harm to my patient. Many of us are concerned about making these reports, which could harm our patients and undermine the doctor-patient relationship,” Dr. Phillips said.

“If I don’t report, what happens? I don’t think we know the answer to that. Some of us may decide we need to part ways with UHC.” Others may decline to participate in the drug manufacturers’ coupon programs beyond simply informing patients that manufacturer assistance is available.

“We’ve watched these copay accumulator policies for several years,” he said. “Some of them are rather opaque, with names like ‘copay savings programs’ or ‘copay value programs.’ But we had not seen a large-scale payer try to do this until now. Let’s face it: If UHC’s policy goes through, you can count the days until we see it from others.”

The Department of Health & Human Services, in its May 2020 final federal “Notice of Benefit and Payment Parameters for 2021,” indicated that individual states have the responsibility to regulate copay accumulator programs. Five states have banned them or restricted their use for individual and small group health plans. Arizona, Illinois, Virginia, and West Virginia passed such laws in 2019, and Georgia did so earlier this year.

“In next year’s state legislative sessions, we’ll make it a priority to pursue similar laws in other states,” Dr. Phillips said. “I’d encourage rheumatologists to educate their patients on the issues and be active in advocating for them.”

Last month, the American College of Rheumatology joined with 11 other medical associations and disease societies asking health insurance giant UnitedHealthcare (UHC) to not proceed with its proposed copay accumulator medical benefit program.

Copay accumulators are policies adopted by insurance companies or their pharmacy benefit managers to exclude patient copayment assistance programs for high-cost drugs, which are promulgated by the drug manufacturers, from being applied to a patient’s annual deductibles or out-of-pocket maximums. The manufacturer’s copay assistance, such as in the form of coupons, is designed to minimize the patient’s out-of-pocket costs. But insurers believe manufacturers will have no pressure to lower the prices of expensive specialty drugs unless patients are unable to afford them. Copay accumulators thus are aimed at giving insurers more leverage in negotiating prices for high-cost drugs.

UHC issued its new copay accumulator protocol for commercial individual and fully insured group plans in early October, effective Jan. 1, 2021, “in order to align employer costs for specialty medications with actual member out of pocket and deductibles,” according to the company’s announcement. In other words, patients will need to pay a higher share of the costs of these medications, said rheumatologist Christopher Phillips, MD, who chairs the Insurance Subcommittee of ACR’s Rheumatologic Care Committee. The annual price of biologic therapies for rheumatologic conditions ranges from $22,000 to $44,000, according to a recent press release from ACR.

The copay accumulator will negate the benefits of manufacturers’ copayment assistance programs for the patient, shifting more of the cost to the patient. With patients being forced to pay a higher share of drug costs for expensive biologic treatments for rheumatoid arthritis, lupus, and other rheumatologic conditions, they’ll stop taking the treatments, Dr. Phillips said.

“In my solo rheumatology practice in Paducah, Kentucky, when I’ve seen this kind of program applied on the pharmacy benefit side, rather than the medical benefit side, almost uniformly patients stop taking the high-cost treatments.” That can lead to disease flares, complications, and permanent disability. The newer rheumatologic drugs can cost $500 to $1,000 per treatment, and in many cases, there’s no generic or lower-cost alternative, he says. “We see policies like this as sacrificing patients to the battle over high drug prices. It’s bad practice, bad for patient outcomes, and nobody – apart from the payer – benefits.”

In ACR’s 2020 Rheumatic Disease Patient Survey, nearly half of 1,109 online survey respondents who had rheumatic diseases reported out-of-pocket costs greater than $1,000 per year for treatment. An IQVIA report from 2016 found that one in four specialty brand prescriptions are abandoned during the deductible phase, three times the rate seen when there is no deductible.

In an Oct. 7 letter to UHC, the 12 groups acknowledged that the drugs targeted by the accumulator policy are expensive. “However, they are also vitally important for our patients.” In addition to the ACR, the organizations involved include the AIDS Institute, American Academy of Dermatology Association, American Academy of Neurology, American College of Gastroenterology, American Gastroenterological Association, American Kidney Fund, Arthritis Foundation, Association for Clinical Oncology, Cancer Support Community, Coalition of State Rheumatology Organizations, and National Multiple Sclerosis Society.

UHC did not reply to questions in time for publication.


 

First large-scale payer to try copay accumulator program

Under UHC’s proposed policy, providers will be required to use UHC’s portal to report payment information received from drug manufacturer copay assistance programs that are applied to patients’ cost share of these drugs through a complex, 14-step “coupon submission process” involving multiple technology interfaces. “My first oath as a physician is to do no harm to my patient. Many of us are concerned about making these reports, which could harm our patients and undermine the doctor-patient relationship,” Dr. Phillips said.

“If I don’t report, what happens? I don’t think we know the answer to that. Some of us may decide we need to part ways with UHC.” Others may decline to participate in the drug manufacturers’ coupon programs beyond simply informing patients that manufacturer assistance is available.

“We’ve watched these copay accumulator policies for several years,” he said. “Some of them are rather opaque, with names like ‘copay savings programs’ or ‘copay value programs.’ But we had not seen a large-scale payer try to do this until now. Let’s face it: If UHC’s policy goes through, you can count the days until we see it from others.”

The Department of Health & Human Services, in its May 2020 final federal “Notice of Benefit and Payment Parameters for 2021,” indicated that individual states have the responsibility to regulate copay accumulator programs. Five states have banned them or restricted their use for individual and small group health plans. Arizona, Illinois, Virginia, and West Virginia passed such laws in 2019, and Georgia did so earlier this year.

“In next year’s state legislative sessions, we’ll make it a priority to pursue similar laws in other states,” Dr. Phillips said. “I’d encourage rheumatologists to educate their patients on the issues and be active in advocating for them.”