MDedge Dermatology

Baricitinib, at a dose of 2 mg a day, demonstrated efficacy in adults with moderate to severe atopic dermatitis up to 52 weeks, integrated data from two trials demonstrated.

Bruce Jancin/MDEdge News

“With long-term therapy, the baricitinib 2 mg response remains stable or slightly improved, compared with week 16 for skin inflammation, itch, sleep, and quality of life,” presenting study author Eric L. Simpson, MD, said during the Revolutionizing Atopic Dermatitis symposium.

Baricitinib is an oral selective Janus kinase 1/JAK2 inhibitor being developed for the treatment of moderate to severe AD in adults who are candidates for systemic therapy. The drug is already approved for AD in Europe at the 2-mg and 4-mg doses. A 16-week placebo-controlled study conducted in North America known as BREEZE-AD5 found that 2 mg of baricitinib improved disease in adults with moderate to severe AD.

For the current analysis, Dr. Simpson, professor of dermatology at Oregon Health and Science University, Portland, and colleagues integrated data from BREEZE-AD5 and BREEZE-AD6, an ongoing, open-label study of BREEZE-AD5, to evaluate the long-term efficacy and safety of baricitinib 2 mg in patients with moderate to severe AD.

At week 16, patients from BREEZE-AD5 who were on baricitinib 2 mg could either continue the trial out to week 52, or they could transition to BREEZE-AD6 if they were nonresponders. The use of low-potency corticosteroids was permitted after week 16 in BREEZE-AD5 and throughout BREEZE-AD6. Endpoints of interest at week 52 in both trials were the proportions of patients with 75% or greater improvement from baseline in the Eczema and Severity Index (EASI75), a Validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) score of 0 or 1, a Dermatology Life Quality Index (DLQI) score of 5 or less, as well as mean SCORing AD (SCORAD) visual analog scales of itch and sleeplessness scores, and the mean percent change from baseline in EASI score.

Dr. Simpson presented data on 146 patients from both trials who were randomized to baricitinib 2 mg. Their mean age was 40 years, 53% were female, 58% were White, 21% were Black, 15% were Asian, and the remainder were from other backgrounds. Their mean duration of AD was 16 years and their average EASI score was 26.6. At weeks 16, 32, and 52, the proportion of patients who achieved an EASI75 response was 40%, 51%, and 49%, respectively, while the mean percent change from baseline in EASI score was –50%, –59%, and –57%.

At weeks 16, 32, and 52, the vIGA-AD responses of 0 or 1 were observed in 27%, 38%, and 31% of patients. The mean SCORAD pruritus score improved from 7.7 at baseline to 4.8 at week 16 and was maintained at weeks 32 (3.8) and 52 (4.3). The mean SCORAD sleeplessness score also improved from 6.5 at baseline to 3.9 at week 16 and remained stable through weeks 32 (3.4) and 52 (3.7).

Finally, among 129 patients who had a baseline DLQI of greater than 5, 39% had DLQI scores of 5 or lower at week 16, compared with 49% at week 32 and 45% at week 52, indicating a small or no effect of AD on quality of life.

The study was sponsored by Eli Lilly, which is developing baricitinib. Dr. Simpson disclosed that he is a consultant to and/or an investigator for several pharmaceutical companies, including Eli Lilly.

[email protected]

Baricitinib, at a dose of 2 mg a day, demonstrated efficacy in adults with moderate to severe atopic dermatitis up to 52 weeks, integrated data from two trials demonstrated.

Bruce Jancin/MDEdge News

“With long-term therapy, the baricitinib 2 mg response remains stable or slightly improved, compared with week 16 for skin inflammation, itch, sleep, and quality of life,” presenting study author Eric L. Simpson, MD, said during the Revolutionizing Atopic Dermatitis symposium.

Baricitinib is an oral selective Janus kinase 1/JAK2 inhibitor being developed for the treatment of moderate to severe AD in adults who are candidates for systemic therapy. The drug is already approved for AD in Europe at the 2-mg and 4-mg doses. A 16-week placebo-controlled study conducted in North America known as BREEZE-AD5 found that 2 mg of baricitinib improved disease in adults with moderate to severe AD.

For the current analysis, Dr. Simpson, professor of dermatology at Oregon Health and Science University, Portland, and colleagues integrated data from BREEZE-AD5 and BREEZE-AD6, an ongoing, open-label study of BREEZE-AD5, to evaluate the long-term efficacy and safety of baricitinib 2 mg in patients with moderate to severe AD.

At week 16, patients from BREEZE-AD5 who were on baricitinib 2 mg could either continue the trial out to week 52, or they could transition to BREEZE-AD6 if they were nonresponders. The use of low-potency corticosteroids was permitted after week 16 in BREEZE-AD5 and throughout BREEZE-AD6. Endpoints of interest at week 52 in both trials were the proportions of patients with 75% or greater improvement from baseline in the Eczema and Severity Index (EASI75), a Validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) score of 0 or 1, a Dermatology Life Quality Index (DLQI) score of 5 or less, as well as mean SCORing AD (SCORAD) visual analog scales of itch and sleeplessness scores, and the mean percent change from baseline in EASI score.

Dr. Simpson presented data on 146 patients from both trials who were randomized to baricitinib 2 mg. Their mean age was 40 years, 53% were female, 58% were White, 21% were Black, 15% were Asian, and the remainder were from other backgrounds. Their mean duration of AD was 16 years and their average EASI score was 26.6. At weeks 16, 32, and 52, the proportion of patients who achieved an EASI75 response was 40%, 51%, and 49%, respectively, while the mean percent change from baseline in EASI score was –50%, –59%, and –57%.

At weeks 16, 32, and 52, the vIGA-AD responses of 0 or 1 were observed in 27%, 38%, and 31% of patients. The mean SCORAD pruritus score improved from 7.7 at baseline to 4.8 at week 16 and was maintained at weeks 32 (3.8) and 52 (4.3). The mean SCORAD sleeplessness score also improved from 6.5 at baseline to 3.9 at week 16 and remained stable through weeks 32 (3.4) and 52 (3.7).

Finally, among 129 patients who had a baseline DLQI of greater than 5, 39% had DLQI scores of 5 or lower at week 16, compared with 49% at week 32 and 45% at week 52, indicating a small or no effect of AD on quality of life.

The study was sponsored by Eli Lilly, which is developing baricitinib. Dr. Simpson disclosed that he is a consultant to and/or an investigator for several pharmaceutical companies, including Eli Lilly.

[email protected]

Baricitinib, at a dose of 2 mg a day, demonstrated efficacy in adults with moderate to severe atopic dermatitis up to 52 weeks, integrated data from two trials demonstrated.

Bruce Jancin/MDEdge News

“With long-term therapy, the baricitinib 2 mg response remains stable or slightly improved, compared with week 16 for skin inflammation, itch, sleep, and quality of life,” presenting study author Eric L. Simpson, MD, said during the Revolutionizing Atopic Dermatitis symposium.

Baricitinib is an oral selective Janus kinase 1/JAK2 inhibitor being developed for the treatment of moderate to severe AD in adults who are candidates for systemic therapy. The drug is already approved for AD in Europe at the 2-mg and 4-mg doses. A 16-week placebo-controlled study conducted in North America known as BREEZE-AD5 found that 2 mg of baricitinib improved disease in adults with moderate to severe AD.

For the current analysis, Dr. Simpson, professor of dermatology at Oregon Health and Science University, Portland, and colleagues integrated data from BREEZE-AD5 and BREEZE-AD6, an ongoing, open-label study of BREEZE-AD5, to evaluate the long-term efficacy and safety of baricitinib 2 mg in patients with moderate to severe AD.

At week 16, patients from BREEZE-AD5 who were on baricitinib 2 mg could either continue the trial out to week 52, or they could transition to BREEZE-AD6 if they were nonresponders. The use of low-potency corticosteroids was permitted after week 16 in BREEZE-AD5 and throughout BREEZE-AD6. Endpoints of interest at week 52 in both trials were the proportions of patients with 75% or greater improvement from baseline in the Eczema and Severity Index (EASI75), a Validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) score of 0 or 1, a Dermatology Life Quality Index (DLQI) score of 5 or less, as well as mean SCORing AD (SCORAD) visual analog scales of itch and sleeplessness scores, and the mean percent change from baseline in EASI score.

Dr. Simpson presented data on 146 patients from both trials who were randomized to baricitinib 2 mg. Their mean age was 40 years, 53% were female, 58% were White, 21% were Black, 15% were Asian, and the remainder were from other backgrounds. Their mean duration of AD was 16 years and their average EASI score was 26.6. At weeks 16, 32, and 52, the proportion of patients who achieved an EASI75 response was 40%, 51%, and 49%, respectively, while the mean percent change from baseline in EASI score was –50%, –59%, and –57%.

At weeks 16, 32, and 52, the vIGA-AD responses of 0 or 1 were observed in 27%, 38%, and 31% of patients. The mean SCORAD pruritus score improved from 7.7 at baseline to 4.8 at week 16 and was maintained at weeks 32 (3.8) and 52 (4.3). The mean SCORAD sleeplessness score also improved from 6.5 at baseline to 3.9 at week 16 and remained stable through weeks 32 (3.4) and 52 (3.7).

Finally, among 129 patients who had a baseline DLQI of greater than 5, 39% had DLQI scores of 5 or lower at week 16, compared with 49% at week 32 and 45% at week 52, indicating a small or no effect of AD on quality of life.

The study was sponsored by Eli Lilly, which is developing baricitinib. Dr. Simpson disclosed that he is a consultant to and/or an investigator for several pharmaceutical companies, including Eli Lilly.

[email protected]

The European Commission (EC) has approved cemiplimab (Libtayo) for the treatment of adults with locally advanced or metastatic basal cell carcinoma (BCC) who progressed on – or could not tolerate – treatment with a hedgehog pathway inhibitor (HHI).

The programmed death-1 (PD-1) inhibitor, which is being jointly developed by Regeneron and Sanofi under a global collaboration agreement, was approved by the Food and Drug Administration for this indication in the United States in February; the FDA granted full approval for its use in patients with locally advanced BCC and accelerated approval for use in patients with metastatic BCC.

The EC’s thumbs-up for cemiplimab as a treatment for BCC marks the third such approval for an advanced cancer in the European Union: The immunotherapy was concurrently approved by the EC for the first-line treatment of adults with advanced non–small cell lung cancer (NSCLC) whose tumor cells have ≥ 50% PD-L1 expression and no EGFR, ALK or ROS1 aberrations, and was approved in 2019 for the treatment of adults with metastatic or locally advanced cutaneous squamous cell carcinoma (CSCC) who are not candidates for curative surgery or curative radiation.

The FDA granted approval of cemiplimab for NSCLC in February, and for CSCC in 2018.

The latest BCC approval is based on data from an ongoing, open-label, prospective phase 2 clinical trial of 119 patients with advanced BCC who were previously treated with an HHI. The objective response rates in cemiplimab-treated patients were 32% (partial responses in 25%; complete responses in 7%) in those with locally advanced BCC, and 29% (partial responses in 26%; complete responses in 3%) in those with metastatic BCC.

About 90% of all patients had a duration of response (DOR) of 6 months or longer. Median DOR was not reached in either group at median follow-up of 16 months for locally advanced BCC and 9 months for metastatic BCC.

The safety profile of cemiplimab has been generally consistent across approved indications. Serious adverse events have been reported in 30% of 816 patients from all four cemiplimab monotherapy pivotal trials, and these led to permanent discontinuation of treatment in 8% of patients.

Immune-related adverse reactions occurred in 22% of patients, and led to permanent discontinuation in 4%. The most common such reactions were hypothyroidism (8%), hyperthyroidism (3%), pneumonitis (3%), hepatitis (2%), colitis (2%) and immune-related skin adverse reactions (2%).

Cemiplimab is administered by intravenous infusion over 30 minutes every 3 weeks until disease progression or unacceptable toxicity. The recommended dose is 350 mg.

A press release from Regeneron notes that research efforts with respect to cemiplimab – both as monotherapy and in combination with other agents – are focused on difficult-to-treat cancers, including advanced NSCLC, cervical cancer, and other solid tumors and blood cancers.

The European Commission (EC) has approved cemiplimab (Libtayo) for the treatment of adults with locally advanced or metastatic basal cell carcinoma (BCC) who progressed on – or could not tolerate – treatment with a hedgehog pathway inhibitor (HHI).

The programmed death-1 (PD-1) inhibitor, which is being jointly developed by Regeneron and Sanofi under a global collaboration agreement, was approved by the Food and Drug Administration for this indication in the United States in February; the FDA granted full approval for its use in patients with locally advanced BCC and accelerated approval for use in patients with metastatic BCC.

The EC’s thumbs-up for cemiplimab as a treatment for BCC marks the third such approval for an advanced cancer in the European Union: The immunotherapy was concurrently approved by the EC for the first-line treatment of adults with advanced non–small cell lung cancer (NSCLC) whose tumor cells have ≥ 50% PD-L1 expression and no EGFR, ALK or ROS1 aberrations, and was approved in 2019 for the treatment of adults with metastatic or locally advanced cutaneous squamous cell carcinoma (CSCC) who are not candidates for curative surgery or curative radiation.

The FDA granted approval of cemiplimab for NSCLC in February, and for CSCC in 2018.

The latest BCC approval is based on data from an ongoing, open-label, prospective phase 2 clinical trial of 119 patients with advanced BCC who were previously treated with an HHI. The objective response rates in cemiplimab-treated patients were 32% (partial responses in 25%; complete responses in 7%) in those with locally advanced BCC, and 29% (partial responses in 26%; complete responses in 3%) in those with metastatic BCC.

About 90% of all patients had a duration of response (DOR) of 6 months or longer. Median DOR was not reached in either group at median follow-up of 16 months for locally advanced BCC and 9 months for metastatic BCC.

The safety profile of cemiplimab has been generally consistent across approved indications. Serious adverse events have been reported in 30% of 816 patients from all four cemiplimab monotherapy pivotal trials, and these led to permanent discontinuation of treatment in 8% of patients.

Immune-related adverse reactions occurred in 22% of patients, and led to permanent discontinuation in 4%. The most common such reactions were hypothyroidism (8%), hyperthyroidism (3%), pneumonitis (3%), hepatitis (2%), colitis (2%) and immune-related skin adverse reactions (2%).

Cemiplimab is administered by intravenous infusion over 30 minutes every 3 weeks until disease progression or unacceptable toxicity. The recommended dose is 350 mg.

A press release from Regeneron notes that research efforts with respect to cemiplimab – both as monotherapy and in combination with other agents – are focused on difficult-to-treat cancers, including advanced NSCLC, cervical cancer, and other solid tumors and blood cancers.

The European Commission (EC) has approved cemiplimab (Libtayo) for the treatment of adults with locally advanced or metastatic basal cell carcinoma (BCC) who progressed on – or could not tolerate – treatment with a hedgehog pathway inhibitor (HHI).

The programmed death-1 (PD-1) inhibitor, which is being jointly developed by Regeneron and Sanofi under a global collaboration agreement, was approved by the Food and Drug Administration for this indication in the United States in February; the FDA granted full approval for its use in patients with locally advanced BCC and accelerated approval for use in patients with metastatic BCC.

The EC’s thumbs-up for cemiplimab as a treatment for BCC marks the third such approval for an advanced cancer in the European Union: The immunotherapy was concurrently approved by the EC for the first-line treatment of adults with advanced non–small cell lung cancer (NSCLC) whose tumor cells have ≥ 50% PD-L1 expression and no EGFR, ALK or ROS1 aberrations, and was approved in 2019 for the treatment of adults with metastatic or locally advanced cutaneous squamous cell carcinoma (CSCC) who are not candidates for curative surgery or curative radiation.

The FDA granted approval of cemiplimab for NSCLC in February, and for CSCC in 2018.

The latest BCC approval is based on data from an ongoing, open-label, prospective phase 2 clinical trial of 119 patients with advanced BCC who were previously treated with an HHI. The objective response rates in cemiplimab-treated patients were 32% (partial responses in 25%; complete responses in 7%) in those with locally advanced BCC, and 29% (partial responses in 26%; complete responses in 3%) in those with metastatic BCC.

About 90% of all patients had a duration of response (DOR) of 6 months or longer. Median DOR was not reached in either group at median follow-up of 16 months for locally advanced BCC and 9 months for metastatic BCC.

The safety profile of cemiplimab has been generally consistent across approved indications. Serious adverse events have been reported in 30% of 816 patients from all four cemiplimab monotherapy pivotal trials, and these led to permanent discontinuation of treatment in 8% of patients.

Immune-related adverse reactions occurred in 22% of patients, and led to permanent discontinuation in 4%. The most common such reactions were hypothyroidism (8%), hyperthyroidism (3%), pneumonitis (3%), hepatitis (2%), colitis (2%) and immune-related skin adverse reactions (2%).

Cemiplimab is administered by intravenous infusion over 30 minutes every 3 weeks until disease progression or unacceptable toxicity. The recommended dose is 350 mg.

A press release from Regeneron notes that research efforts with respect to cemiplimab – both as monotherapy and in combination with other agents – are focused on difficult-to-treat cancers, including advanced NSCLC, cervical cancer, and other solid tumors and blood cancers.

The risk of amputations in persons with type 1 diabetes in Sweden has decreased over time, suggesting an improvement in the course of disease for these individuals, according to a national registry analysis.

Balkonsky/Thinkstock

The incidence of any amputation trended downward from 2011 to 2019, Sara Hallström, MD, reported at the annual scientific sessions of the American Diabetes Association.

Levels of hemoglobin A1c have also trended downward over time in Sweden among those with type 1 diabetes, while renal function has remained stable among patients who did not undergo amputations, Dr. Hallström said in a virtual presentation.

“Observing stable renal function and decreasing levels of [hemoglobin] A1c, along with decreasing incidence of amputation, indicates a shift in the prognosis of persons with type 1 diabetes,” she said.
 

Drilling down on amputation risk in type 1 diabetes

Lower-extremity amputation is a major source of disability and distress in people with diabetes, and also poses a significant financial burden for the health care system, according to Dr. Hallström of Sahlgrenska University Hospital and the University of Gothenburg (Sweden).

“Limb loss due to amputation is not seldom a final outcome of diabetic foot ulcers,” she said in the presentation.

Most studies of amputation incidence and risk factors have grouped patients with different types of diabetes, though a few recent studies have singled out type 1 diabetes.

Among these is a 2019 study indicating a 40-fold higher risk of amputation among individuals with type 1 diabetes, compared with the general population, based on analysis of Swedish National Diabetes Register data from 1998 to 2013.
 

Trends over time

In the present study, Dr. Hallström and coinvestigators queried that same Swedish registry and identified 46,008 individuals with type 1 diabetes from 1998 to 2019. The mean age was 32.5 years and 55% were male. Overall, 1,519 of these individuals (3.3%) underwent amputation.

The incidence of any amputation fluctuated from 1998 to 2011, followed by a “decreasing trend over time” from 2011 to 2019, Dr. Hallström said.

The incidence of amputation per 1,000 patient-years was 2.84 in the earliest time period of 1998-2001, decreasing to 1.64 in 2017-2019.

Levels of A1c decreased over time, starting at 2012, both in participants with and without amputations, Dr. Hallström said. Renal function over that period remained stable in persons without amputation, and showed a decreasing trend in persons with amputation.

Compared with individuals with no amputations, those undergoing amputation were older (50 years vs. 32 years), had a longer duration of diabetes (34.9 years vs. 16.5 years), and had higher mean A1c, Dr. Hellström said. The amputee group also included a higher proportion of smokers, at 19.4% versus 14.0%, data show.

Risk factors for amputation included renal dysfunction, hyperglycemia, older age, smoking, hypertension, and cardiovascular comorbidities, according to the researcher.
 

U.S. amputations on the rise overall

While authors say results of this study point to a potentially improved prognosis for individuals with type 1 diabetes in Sweden, Robert A. Gabbay, MD, PhD, chief scientific and medical officer of the ADA, said amputation rates remains “concerning” based on U.S. data focused largely on type 2 diabetes.

“The amputation rate is unfortunately rising,” he said. “Sadly, this continues to be an issue.”

Significant health disparities persist, he added, with Black Americans having two- to threefold higher rates of amputations.

To help reduce amputation rates, clinicians should be asking patient about claudication and using simple screening techniques such as inspecting patient’s feet. “The big deal here is preventing ulcer formation, because once the ulcer forms, it often doesn’t heal, and it’s a downward spiral,” he said.

In addition, recent research suggests seeking a second opinion may help: “Many of those amputations could be avoided, in part because people aren’t aware of some of the treatments that can open up the arteries and reestablish blood flow,” he added.

Dr. Hallström reported no conflicts of interest. One coauthor on the study provided disclosures related to Abbott, AstraZeneca, Boehringer Ingelheim, Lilly Diabetes, and Novo Nordisk.

The risk of amputations in persons with type 1 diabetes in Sweden has decreased over time, suggesting an improvement in the course of disease for these individuals, according to a national registry analysis.

Balkonsky/Thinkstock

The incidence of any amputation trended downward from 2011 to 2019, Sara Hallström, MD, reported at the annual scientific sessions of the American Diabetes Association.

Levels of hemoglobin A1c have also trended downward over time in Sweden among those with type 1 diabetes, while renal function has remained stable among patients who did not undergo amputations, Dr. Hallström said in a virtual presentation.

“Observing stable renal function and decreasing levels of [hemoglobin] A1c, along with decreasing incidence of amputation, indicates a shift in the prognosis of persons with type 1 diabetes,” she said.
 

Drilling down on amputation risk in type 1 diabetes

Lower-extremity amputation is a major source of disability and distress in people with diabetes, and also poses a significant financial burden for the health care system, according to Dr. Hallström of Sahlgrenska University Hospital and the University of Gothenburg (Sweden).

“Limb loss due to amputation is not seldom a final outcome of diabetic foot ulcers,” she said in the presentation.

Most studies of amputation incidence and risk factors have grouped patients with different types of diabetes, though a few recent studies have singled out type 1 diabetes.

Among these is a 2019 study indicating a 40-fold higher risk of amputation among individuals with type 1 diabetes, compared with the general population, based on analysis of Swedish National Diabetes Register data from 1998 to 2013.
 

Trends over time

In the present study, Dr. Hallström and coinvestigators queried that same Swedish registry and identified 46,008 individuals with type 1 diabetes from 1998 to 2019. The mean age was 32.5 years and 55% were male. Overall, 1,519 of these individuals (3.3%) underwent amputation.

The incidence of any amputation fluctuated from 1998 to 2011, followed by a “decreasing trend over time” from 2011 to 2019, Dr. Hallström said.

The incidence of amputation per 1,000 patient-years was 2.84 in the earliest time period of 1998-2001, decreasing to 1.64 in 2017-2019.

Levels of A1c decreased over time, starting at 2012, both in participants with and without amputations, Dr. Hallström said. Renal function over that period remained stable in persons without amputation, and showed a decreasing trend in persons with amputation.

Compared with individuals with no amputations, those undergoing amputation were older (50 years vs. 32 years), had a longer duration of diabetes (34.9 years vs. 16.5 years), and had higher mean A1c, Dr. Hellström said. The amputee group also included a higher proportion of smokers, at 19.4% versus 14.0%, data show.

Risk factors for amputation included renal dysfunction, hyperglycemia, older age, smoking, hypertension, and cardiovascular comorbidities, according to the researcher.
 

U.S. amputations on the rise overall

While authors say results of this study point to a potentially improved prognosis for individuals with type 1 diabetes in Sweden, Robert A. Gabbay, MD, PhD, chief scientific and medical officer of the ADA, said amputation rates remains “concerning” based on U.S. data focused largely on type 2 diabetes.

“The amputation rate is unfortunately rising,” he said. “Sadly, this continues to be an issue.”

Significant health disparities persist, he added, with Black Americans having two- to threefold higher rates of amputations.

To help reduce amputation rates, clinicians should be asking patient about claudication and using simple screening techniques such as inspecting patient’s feet. “The big deal here is preventing ulcer formation, because once the ulcer forms, it often doesn’t heal, and it’s a downward spiral,” he said.

In addition, recent research suggests seeking a second opinion may help: “Many of those amputations could be avoided, in part because people aren’t aware of some of the treatments that can open up the arteries and reestablish blood flow,” he added.

Dr. Hallström reported no conflicts of interest. One coauthor on the study provided disclosures related to Abbott, AstraZeneca, Boehringer Ingelheim, Lilly Diabetes, and Novo Nordisk.

The risk of amputations in persons with type 1 diabetes in Sweden has decreased over time, suggesting an improvement in the course of disease for these individuals, according to a national registry analysis.

Balkonsky/Thinkstock

The incidence of any amputation trended downward from 2011 to 2019, Sara Hallström, MD, reported at the annual scientific sessions of the American Diabetes Association.

Levels of hemoglobin A1c have also trended downward over time in Sweden among those with type 1 diabetes, while renal function has remained stable among patients who did not undergo amputations, Dr. Hallström said in a virtual presentation.

“Observing stable renal function and decreasing levels of [hemoglobin] A1c, along with decreasing incidence of amputation, indicates a shift in the prognosis of persons with type 1 diabetes,” she said.
 

Drilling down on amputation risk in type 1 diabetes

Lower-extremity amputation is a major source of disability and distress in people with diabetes, and also poses a significant financial burden for the health care system, according to Dr. Hallström of Sahlgrenska University Hospital and the University of Gothenburg (Sweden).

“Limb loss due to amputation is not seldom a final outcome of diabetic foot ulcers,” she said in the presentation.

Most studies of amputation incidence and risk factors have grouped patients with different types of diabetes, though a few recent studies have singled out type 1 diabetes.

Among these is a 2019 study indicating a 40-fold higher risk of amputation among individuals with type 1 diabetes, compared with the general population, based on analysis of Swedish National Diabetes Register data from 1998 to 2013.
 

Trends over time

In the present study, Dr. Hallström and coinvestigators queried that same Swedish registry and identified 46,008 individuals with type 1 diabetes from 1998 to 2019. The mean age was 32.5 years and 55% were male. Overall, 1,519 of these individuals (3.3%) underwent amputation.

The incidence of any amputation fluctuated from 1998 to 2011, followed by a “decreasing trend over time” from 2011 to 2019, Dr. Hallström said.

The incidence of amputation per 1,000 patient-years was 2.84 in the earliest time period of 1998-2001, decreasing to 1.64 in 2017-2019.

Levels of A1c decreased over time, starting at 2012, both in participants with and without amputations, Dr. Hallström said. Renal function over that period remained stable in persons without amputation, and showed a decreasing trend in persons with amputation.

Compared with individuals with no amputations, those undergoing amputation were older (50 years vs. 32 years), had a longer duration of diabetes (34.9 years vs. 16.5 years), and had higher mean A1c, Dr. Hellström said. The amputee group also included a higher proportion of smokers, at 19.4% versus 14.0%, data show.

Risk factors for amputation included renal dysfunction, hyperglycemia, older age, smoking, hypertension, and cardiovascular comorbidities, according to the researcher.
 

U.S. amputations on the rise overall

While authors say results of this study point to a potentially improved prognosis for individuals with type 1 diabetes in Sweden, Robert A. Gabbay, MD, PhD, chief scientific and medical officer of the ADA, said amputation rates remains “concerning” based on U.S. data focused largely on type 2 diabetes.

“The amputation rate is unfortunately rising,” he said. “Sadly, this continues to be an issue.”

Significant health disparities persist, he added, with Black Americans having two- to threefold higher rates of amputations.

To help reduce amputation rates, clinicians should be asking patient about claudication and using simple screening techniques such as inspecting patient’s feet. “The big deal here is preventing ulcer formation, because once the ulcer forms, it often doesn’t heal, and it’s a downward spiral,” he said.

In addition, recent research suggests seeking a second opinion may help: “Many of those amputations could be avoided, in part because people aren’t aware of some of the treatments that can open up the arteries and reestablish blood flow,” he added.

Dr. Hallström reported no conflicts of interest. One coauthor on the study provided disclosures related to Abbott, AstraZeneca, Boehringer Ingelheim, Lilly Diabetes, and Novo Nordisk.

Treating the needs of patients of color requires an understanding of differences that may not be readily apparent, a dermatologist told colleagues. For example, clinicians generally understand what White patients are talking about when they mention acne scarring, but Black patients have a different perception of the term that may be misinterpreted in the doctor’s office.

“Scarring is not usually what they’re talking about, although they may have some of that as well. They’re [typically] talking about what we know as postinflammatory hyperpigmentation, not scarring. So right away, you have to clarify,” Amy McMichael, MD, professor and chair of dermatology at Wake Forest Baptist Medical Center in Winston-Salem, N.C., said in a presentation at the Inaugural Symposium for Inflammatory Skin Disease. “When you’re talking about scarring, do you mean the dark spots? What exactly are you concerned about?”

Dr. McMichael highlighted a 2014 study that reported the results of a survey of 208 women (51% were White; 49% were non-White), which included 51 Black, 23 Hispanic, and 16 Asian women aged 25-45 (mean age, 35) with 25 or more lesions. White women were more troubled by facial acne than were women of color (89% vs. 76%, respectively, P < .05), and they were more likely to say lesion clearance was most important to them (58% vs. 32%, respectively, P < .001).

Meanwhile, non-White women were much more likely than were White women to say that clearance of postinflammatory hyperpigmentation was most important to them (42% vs. 8%, respectively, P < .0001).

“Seventy percent of [non-White women] felt that their race and ethnicity required targeted attention [in treatment], and two-thirds desired acne treatment that was designed to meet the needs of their skin type,” Dr. McMichael said. “If you don’t address the issues, if you don’t talk about the pigmentation with them or explain how you’re going to address it, people don’t feel heard. They don’t feel like they’ve really seen a dermatologist who understands their needs.”

She added that it’s crucial to ask about over-the-counter products. “If you don’t discuss them, they’ll assume that what they’re doing is okay.” She warns her patients against using and exposing their skin and face to cocoa butter and oils such as tea tree oil.

Research has suggested that among people of color, Blacks and Hispanics are most likely to experience dyspigmentation and scarring, Dr. McMichael said. She advised colleagues to be aware of pomade acne in these two groups of patients. Pomade acne appears along the hair line and is caused by the use of hair products. She also cautioned about acne cosmetica, which can be triggered by products such as makeup, used to cover up acne and postinflammatory hyperpigmentation.

As for acne treatments, Dr. McMichael highlighted a long list of familiar topical and oral agents and procedural options. Less familiar strategies include laser and light-based therapies, she said.

As for up-and-coming options, she pointed to topical minocycline, “which allows us to use an anti-inflammatory agent topically rather than orally when we’re trying to get away from using a lot of oral antibiotics.”

Also consider whether female patients have polycystic ovary syndrome, she said. “Then you might consider spironolactone. I certainly use a lot more of that these days to try to avoid long-term oral antibiotics.”

She recommended earlier use of isotretinoin in patients overall, and she urged colleagues to proceed with their standard retinoid approaches. However, she noted that she lets patients know that she’ll focus first on treating the acne itself and then work on the dark spots in later treatments. “If you give people a bleaching agent in the beginning, they’re going to stop using their main products, and they’re going to chase those dark spots. That’s just something that they can’t help doing.”

Dr. McMichael disclosed investigator and consultant relationships with multiple drug makers.

Treating the needs of patients of color requires an understanding of differences that may not be readily apparent, a dermatologist told colleagues. For example, clinicians generally understand what White patients are talking about when they mention acne scarring, but Black patients have a different perception of the term that may be misinterpreted in the doctor’s office.

“Scarring is not usually what they’re talking about, although they may have some of that as well. They’re [typically] talking about what we know as postinflammatory hyperpigmentation, not scarring. So right away, you have to clarify,” Amy McMichael, MD, professor and chair of dermatology at Wake Forest Baptist Medical Center in Winston-Salem, N.C., said in a presentation at the Inaugural Symposium for Inflammatory Skin Disease. “When you’re talking about scarring, do you mean the dark spots? What exactly are you concerned about?”

Dr. McMichael highlighted a 2014 study that reported the results of a survey of 208 women (51% were White; 49% were non-White), which included 51 Black, 23 Hispanic, and 16 Asian women aged 25-45 (mean age, 35) with 25 or more lesions. White women were more troubled by facial acne than were women of color (89% vs. 76%, respectively, P < .05), and they were more likely to say lesion clearance was most important to them (58% vs. 32%, respectively, P < .001).

Meanwhile, non-White women were much more likely than were White women to say that clearance of postinflammatory hyperpigmentation was most important to them (42% vs. 8%, respectively, P < .0001).

“Seventy percent of [non-White women] felt that their race and ethnicity required targeted attention [in treatment], and two-thirds desired acne treatment that was designed to meet the needs of their skin type,” Dr. McMichael said. “If you don’t address the issues, if you don’t talk about the pigmentation with them or explain how you’re going to address it, people don’t feel heard. They don’t feel like they’ve really seen a dermatologist who understands their needs.”

She added that it’s crucial to ask about over-the-counter products. “If you don’t discuss them, they’ll assume that what they’re doing is okay.” She warns her patients against using and exposing their skin and face to cocoa butter and oils such as tea tree oil.

Research has suggested that among people of color, Blacks and Hispanics are most likely to experience dyspigmentation and scarring, Dr. McMichael said. She advised colleagues to be aware of pomade acne in these two groups of patients. Pomade acne appears along the hair line and is caused by the use of hair products. She also cautioned about acne cosmetica, which can be triggered by products such as makeup, used to cover up acne and postinflammatory hyperpigmentation.

As for acne treatments, Dr. McMichael highlighted a long list of familiar topical and oral agents and procedural options. Less familiar strategies include laser and light-based therapies, she said.

As for up-and-coming options, she pointed to topical minocycline, “which allows us to use an anti-inflammatory agent topically rather than orally when we’re trying to get away from using a lot of oral antibiotics.”

Also consider whether female patients have polycystic ovary syndrome, she said. “Then you might consider spironolactone. I certainly use a lot more of that these days to try to avoid long-term oral antibiotics.”

She recommended earlier use of isotretinoin in patients overall, and she urged colleagues to proceed with their standard retinoid approaches. However, she noted that she lets patients know that she’ll focus first on treating the acne itself and then work on the dark spots in later treatments. “If you give people a bleaching agent in the beginning, they’re going to stop using their main products, and they’re going to chase those dark spots. That’s just something that they can’t help doing.”

Dr. McMichael disclosed investigator and consultant relationships with multiple drug makers.

Treating the needs of patients of color requires an understanding of differences that may not be readily apparent, a dermatologist told colleagues. For example, clinicians generally understand what White patients are talking about when they mention acne scarring, but Black patients have a different perception of the term that may be misinterpreted in the doctor’s office.

“Scarring is not usually what they’re talking about, although they may have some of that as well. They’re [typically] talking about what we know as postinflammatory hyperpigmentation, not scarring. So right away, you have to clarify,” Amy McMichael, MD, professor and chair of dermatology at Wake Forest Baptist Medical Center in Winston-Salem, N.C., said in a presentation at the Inaugural Symposium for Inflammatory Skin Disease. “When you’re talking about scarring, do you mean the dark spots? What exactly are you concerned about?”

Dr. McMichael highlighted a 2014 study that reported the results of a survey of 208 women (51% were White; 49% were non-White), which included 51 Black, 23 Hispanic, and 16 Asian women aged 25-45 (mean age, 35) with 25 or more lesions. White women were more troubled by facial acne than were women of color (89% vs. 76%, respectively, P < .05), and they were more likely to say lesion clearance was most important to them (58% vs. 32%, respectively, P < .001).

Meanwhile, non-White women were much more likely than were White women to say that clearance of postinflammatory hyperpigmentation was most important to them (42% vs. 8%, respectively, P < .0001).

“Seventy percent of [non-White women] felt that their race and ethnicity required targeted attention [in treatment], and two-thirds desired acne treatment that was designed to meet the needs of their skin type,” Dr. McMichael said. “If you don’t address the issues, if you don’t talk about the pigmentation with them or explain how you’re going to address it, people don’t feel heard. They don’t feel like they’ve really seen a dermatologist who understands their needs.”

She added that it’s crucial to ask about over-the-counter products. “If you don’t discuss them, they’ll assume that what they’re doing is okay.” She warns her patients against using and exposing their skin and face to cocoa butter and oils such as tea tree oil.

Research has suggested that among people of color, Blacks and Hispanics are most likely to experience dyspigmentation and scarring, Dr. McMichael said. She advised colleagues to be aware of pomade acne in these two groups of patients. Pomade acne appears along the hair line and is caused by the use of hair products. She also cautioned about acne cosmetica, which can be triggered by products such as makeup, used to cover up acne and postinflammatory hyperpigmentation.

As for acne treatments, Dr. McMichael highlighted a long list of familiar topical and oral agents and procedural options. Less familiar strategies include laser and light-based therapies, she said.

As for up-and-coming options, she pointed to topical minocycline, “which allows us to use an anti-inflammatory agent topically rather than orally when we’re trying to get away from using a lot of oral antibiotics.”

Also consider whether female patients have polycystic ovary syndrome, she said. “Then you might consider spironolactone. I certainly use a lot more of that these days to try to avoid long-term oral antibiotics.”

She recommended earlier use of isotretinoin in patients overall, and she urged colleagues to proceed with their standard retinoid approaches. However, she noted that she lets patients know that she’ll focus first on treating the acne itself and then work on the dark spots in later treatments. “If you give people a bleaching agent in the beginning, they’re going to stop using their main products, and they’re going to chase those dark spots. That’s just something that they can’t help doing.”

Dr. McMichael disclosed investigator and consultant relationships with multiple drug makers.

After treatment with ruxolitinib cream for 52 weeks, between 60% and 80% of atopic dermatitis patients maintained clear or almost clear skin, with no safety signals, results from a long-term analysis of clinical trial data showed.

“The incidence of application-site reactions was low, and there were no clinically meaningful changes or trends in hematologic parameters,” Kim Papp, MD, PhD, said during the Revolutionizing Atopic Dermatitis symposium.

Ruxolitinib cream is a selective Janus kinase 1/JAK2 inhibitor being developed by Incyte for the treatment of atopic dermatitis (AD).

According to a press release from the company, the Food and Drug Administration has extended the New Drug Application review period for the agent by 3 months to September 2021. If approved, it would become first topical JAK inhibitor for use in dermatology.

In two phase 3, randomized studies of identical design involving 1,249 patients aged 12 and older with AD – TRuE-AD1 and TRuE-AD2 – ruxolitinib cream demonstrated anti-inflammatory activity, with rapid and sustained antipruritic action, compared with vehicle. To be eligible for the trials patients with an Investigator’s Global Assessment (IGA) score of 2 or 3 and 3%-20% of affected body surface area (BSA) were randomized (2:2:1) to twice-daily 0.75% ruxolitinib cream, 1.5% ruxolitinib cream, or vehicle cream for 8 continuous weeks.

A recently published report found that significantly more patients in TRuE-AD1 and TRuE-AD2 achieved IGA treatment success with 0.75% (50% vs. 39%, respectively) and 1.5% ruxolitinib cream (53.8% vs. 51.3%), compared with vehicle (15.1% vs. 7.6%; P < .0001) at week 8. In addition, significant reductions in itch, compared with vehicle, were reported within 12 hours of first applying 1.5% ruxolitinib cream (P < .05).
 

Longterm data

During the symposium, Dr. Papp presented long-term safety data of ruxolitinib cream in patients who were followed for an additional 44 weeks. Those initially randomized to vehicle were rerandomized 1:1 (blinded) to either ruxolitinib cream regimen. They were instructed to treat skin areas with active AD only and to stop treatment 3 days after clearance of lesions, and to restart treatment with ruxolitinib cream at the first sign of recurrence. Safety and tolerability were assessed by frequency and severity of adverse events, while disease control was measured by the proportion of patients with an IGA score of 0 or 1 and the affected BSA.

Dr. Papp, a dermatologist and founder of Probity Medical Research, Waterloo, Ont., reported that 543 patients from TRuE-AD1 and 530 from TRuE-AD2 entered the long-term analysis and that about 78% of these patients completed the study. From weeks 12 to 52, the proportion of patients with an IGA score of 0 or 1 with 0.75% and 1.5% ruxolitinib cream ranged from 62%-77% and 67%-77%, respectively, in TRuE-AD1 to 60%-77% and 72%-80% in TRuE-AD2.

The measured mean total affected BSA was less than 3% throughout the follow-up period in the 1.5% ruxolitinib cream arm in TRuE-AD1 and TRuE-AD2 and was less than 3% in the 0.75% ruxolitinib cream arm during most of the study period.

In a pooled safety analysis, treatment-emergent adverse events (TEAEs) were reported in 60% and 54% of patients who applied 0.75% and 1.5% ruxolitinib cream, respectively, over 44 weeks. The frequency of application-site reactions remained low. Specifically, treatment-related adverse events were reported in 5% of patients who applied 0.75% ruxolitinib cream and in 3% of patients who applied 1.5% ruxolitinib cream; none were serious. TEAEs led to discontinuation in 2% of patients in the 0.75% ruxolitinib cream group, and no patients in the 1.5% ruxolitinib cream group.

“The most common treatment adverse events were upper respiratory tract infections and nasopharyngitis,” Dr. Papp said. “When looking at exposure-adjusted adverse events, we see that there is a high degree of similarity between any of the TEAEs across all of the treatment groups in both studies. We also see that it was patients on the vehicle who experienced the greatest number of application-site reactions.”

Dr. Papp disclosed that he has received honoraria or clinical research grants as a consultant, speaker, scientific officer, advisory board member, and/or steering committee member for several pharmaceutical companies, including Incyte.

[email protected]

After treatment with ruxolitinib cream for 52 weeks, between 60% and 80% of atopic dermatitis patients maintained clear or almost clear skin, with no safety signals, results from a long-term analysis of clinical trial data showed.

“The incidence of application-site reactions was low, and there were no clinically meaningful changes or trends in hematologic parameters,” Kim Papp, MD, PhD, said during the Revolutionizing Atopic Dermatitis symposium.

Ruxolitinib cream is a selective Janus kinase 1/JAK2 inhibitor being developed by Incyte for the treatment of atopic dermatitis (AD).

According to a press release from the company, the Food and Drug Administration has extended the New Drug Application review period for the agent by 3 months to September 2021. If approved, it would become first topical JAK inhibitor for use in dermatology.

In two phase 3, randomized studies of identical design involving 1,249 patients aged 12 and older with AD – TRuE-AD1 and TRuE-AD2 – ruxolitinib cream demonstrated anti-inflammatory activity, with rapid and sustained antipruritic action, compared with vehicle. To be eligible for the trials patients with an Investigator’s Global Assessment (IGA) score of 2 or 3 and 3%-20% of affected body surface area (BSA) were randomized (2:2:1) to twice-daily 0.75% ruxolitinib cream, 1.5% ruxolitinib cream, or vehicle cream for 8 continuous weeks.

A recently published report found that significantly more patients in TRuE-AD1 and TRuE-AD2 achieved IGA treatment success with 0.75% (50% vs. 39%, respectively) and 1.5% ruxolitinib cream (53.8% vs. 51.3%), compared with vehicle (15.1% vs. 7.6%; P < .0001) at week 8. In addition, significant reductions in itch, compared with vehicle, were reported within 12 hours of first applying 1.5% ruxolitinib cream (P < .05).
 

Longterm data

During the symposium, Dr. Papp presented long-term safety data of ruxolitinib cream in patients who were followed for an additional 44 weeks. Those initially randomized to vehicle were rerandomized 1:1 (blinded) to either ruxolitinib cream regimen. They were instructed to treat skin areas with active AD only and to stop treatment 3 days after clearance of lesions, and to restart treatment with ruxolitinib cream at the first sign of recurrence. Safety and tolerability were assessed by frequency and severity of adverse events, while disease control was measured by the proportion of patients with an IGA score of 0 or 1 and the affected BSA.

Dr. Papp, a dermatologist and founder of Probity Medical Research, Waterloo, Ont., reported that 543 patients from TRuE-AD1 and 530 from TRuE-AD2 entered the long-term analysis and that about 78% of these patients completed the study. From weeks 12 to 52, the proportion of patients with an IGA score of 0 or 1 with 0.75% and 1.5% ruxolitinib cream ranged from 62%-77% and 67%-77%, respectively, in TRuE-AD1 to 60%-77% and 72%-80% in TRuE-AD2.

The measured mean total affected BSA was less than 3% throughout the follow-up period in the 1.5% ruxolitinib cream arm in TRuE-AD1 and TRuE-AD2 and was less than 3% in the 0.75% ruxolitinib cream arm during most of the study period.

In a pooled safety analysis, treatment-emergent adverse events (TEAEs) were reported in 60% and 54% of patients who applied 0.75% and 1.5% ruxolitinib cream, respectively, over 44 weeks. The frequency of application-site reactions remained low. Specifically, treatment-related adverse events were reported in 5% of patients who applied 0.75% ruxolitinib cream and in 3% of patients who applied 1.5% ruxolitinib cream; none were serious. TEAEs led to discontinuation in 2% of patients in the 0.75% ruxolitinib cream group, and no patients in the 1.5% ruxolitinib cream group.

“The most common treatment adverse events were upper respiratory tract infections and nasopharyngitis,” Dr. Papp said. “When looking at exposure-adjusted adverse events, we see that there is a high degree of similarity between any of the TEAEs across all of the treatment groups in both studies. We also see that it was patients on the vehicle who experienced the greatest number of application-site reactions.”

Dr. Papp disclosed that he has received honoraria or clinical research grants as a consultant, speaker, scientific officer, advisory board member, and/or steering committee member for several pharmaceutical companies, including Incyte.

[email protected]

After treatment with ruxolitinib cream for 52 weeks, between 60% and 80% of atopic dermatitis patients maintained clear or almost clear skin, with no safety signals, results from a long-term analysis of clinical trial data showed.

“The incidence of application-site reactions was low, and there were no clinically meaningful changes or trends in hematologic parameters,” Kim Papp, MD, PhD, said during the Revolutionizing Atopic Dermatitis symposium.

Ruxolitinib cream is a selective Janus kinase 1/JAK2 inhibitor being developed by Incyte for the treatment of atopic dermatitis (AD).

According to a press release from the company, the Food and Drug Administration has extended the New Drug Application review period for the agent by 3 months to September 2021. If approved, it would become first topical JAK inhibitor for use in dermatology.

In two phase 3, randomized studies of identical design involving 1,249 patients aged 12 and older with AD – TRuE-AD1 and TRuE-AD2 – ruxolitinib cream demonstrated anti-inflammatory activity, with rapid and sustained antipruritic action, compared with vehicle. To be eligible for the trials patients with an Investigator’s Global Assessment (IGA) score of 2 or 3 and 3%-20% of affected body surface area (BSA) were randomized (2:2:1) to twice-daily 0.75% ruxolitinib cream, 1.5% ruxolitinib cream, or vehicle cream for 8 continuous weeks.

A recently published report found that significantly more patients in TRuE-AD1 and TRuE-AD2 achieved IGA treatment success with 0.75% (50% vs. 39%, respectively) and 1.5% ruxolitinib cream (53.8% vs. 51.3%), compared with vehicle (15.1% vs. 7.6%; P < .0001) at week 8. In addition, significant reductions in itch, compared with vehicle, were reported within 12 hours of first applying 1.5% ruxolitinib cream (P < .05).
 

Longterm data

During the symposium, Dr. Papp presented long-term safety data of ruxolitinib cream in patients who were followed for an additional 44 weeks. Those initially randomized to vehicle were rerandomized 1:1 (blinded) to either ruxolitinib cream regimen. They were instructed to treat skin areas with active AD only and to stop treatment 3 days after clearance of lesions, and to restart treatment with ruxolitinib cream at the first sign of recurrence. Safety and tolerability were assessed by frequency and severity of adverse events, while disease control was measured by the proportion of patients with an IGA score of 0 or 1 and the affected BSA.

Dr. Papp, a dermatologist and founder of Probity Medical Research, Waterloo, Ont., reported that 543 patients from TRuE-AD1 and 530 from TRuE-AD2 entered the long-term analysis and that about 78% of these patients completed the study. From weeks 12 to 52, the proportion of patients with an IGA score of 0 or 1 with 0.75% and 1.5% ruxolitinib cream ranged from 62%-77% and 67%-77%, respectively, in TRuE-AD1 to 60%-77% and 72%-80% in TRuE-AD2.

The measured mean total affected BSA was less than 3% throughout the follow-up period in the 1.5% ruxolitinib cream arm in TRuE-AD1 and TRuE-AD2 and was less than 3% in the 0.75% ruxolitinib cream arm during most of the study period.

In a pooled safety analysis, treatment-emergent adverse events (TEAEs) were reported in 60% and 54% of patients who applied 0.75% and 1.5% ruxolitinib cream, respectively, over 44 weeks. The frequency of application-site reactions remained low. Specifically, treatment-related adverse events were reported in 5% of patients who applied 0.75% ruxolitinib cream and in 3% of patients who applied 1.5% ruxolitinib cream; none were serious. TEAEs led to discontinuation in 2% of patients in the 0.75% ruxolitinib cream group, and no patients in the 1.5% ruxolitinib cream group.

“The most common treatment adverse events were upper respiratory tract infections and nasopharyngitis,” Dr. Papp said. “When looking at exposure-adjusted adverse events, we see that there is a high degree of similarity between any of the TEAEs across all of the treatment groups in both studies. We also see that it was patients on the vehicle who experienced the greatest number of application-site reactions.”

Dr. Papp disclosed that he has received honoraria or clinical research grants as a consultant, speaker, scientific officer, advisory board member, and/or steering committee member for several pharmaceutical companies, including Incyte.

[email protected]

It was a 95° F day in July 2015, and emergency physician Martin Maag, MD, was driving down Bee Ridge Road, a busy seven-lane thoroughfare in Sarasota, Fla., on his way home from a family dinner. To distance himself from a truck blowing black smoke, Dr. Maag says he had just passed some vehicles, when a motorcycle flew past him in the turning lane and the passenger flipped him off.

“I started laughing because I knew we were coming up to a red light,” said Dr. Maag. “When we pulled up to the light, I put my window down and said: ‘Hey, you ought to be a little more careful about who you’re flipping off! You never know who it might be and what they might do.’ ”

The female passenger cursed at Dr. Maag, and the two traded profanities. The male driver then told Dr. Maag: “Get out of the car, old man,” according to Dr. Maag. Fuming, Dr. Maag got out of his black Tesla, and the two men met in the middle of the street.

“As soon as I got close enough to see him, I could tell he really looked young,” Dr. Maag recalls. “I said: ‘You’re like 12 years old. I’m going to end up beating your ass and then I’m going to go to jail. Go get on your bike, and ride home to your mom.’ I don’t remember what he said to me, but I spun around and said: ‘If you want to act like a man, meet me up the street in a parking lot and let’s have at it like men.’ ”

The motorcyclist got back on his white Suzuki and sped off, and Dr. Maag followed. Both vehicles went racing down the road, swerving between cars, and reaching speeds of 100 miles per hour, Dr. Maag said. At one point, Dr. Maag says he drove in front of the motorcyclist to slow him down, and the motorcycle clipped the back of his car. No one was seriously hurt, but soon Dr. Maag was in the back of a police cruiser headed to jail.

Dr. Maag wishes he could take back his actions that summer day 6 years ago. Those few minutes of fury have had lasting effects on the doctor’s life. The incident resulted in criminal charges, a jail sentence, thousands of dollars in legal fees, and a 3-year departure from emergency medicine. Although Dr. Maag did not lose his medical license as a result of the incident, the physician’s Medicare billing privileges were suspended because of a federal provision that ties some felonies to enrollment revocations.

Dr. Maag, 61, shared his story with this news organization to warn other physicians about the wide-ranging career ramifications that can happen as a result of offenses unrelated to medicine. 

“Every doctor, every health professional needs to know that there are a lot of consequences that go with our actions outside of work,” he said. “In my situation, what happened had nothing to do with medicine, it had nothing to do with patients, it had nothing to do my professional demeanor. But yet it affected my entire career, and I lost the ability to practice emergency medicine for 3 years. Three years for any doctor is a long time. Three years for emergency medicine is a lifetime.”
 

The physician ends up in jail

After the collision, Dr. Maag pulled over in a parking lot and dialed 911. Several passing motorists did the same. It appeared the biker was trying to get away, and Dr. Maag was concerned about the damage to his Tesla, he said. 

When police arrived, they heard very different accounts of what happened. The motorcyclist and his girlfriend claimed Dr. Maag was the aggressor during the altercation, and that he deliberately tried to hit them with his vehicle. Two witnesses at the scene said they had watched Dr. Maag pursue the motorcycle in his vehicle, and that they believed he crossed into their lane intentionally to strike the motorcycle, according to police reports.

“[The motorcyclist] stated that the vehicle struck his right foot when it hit the motorcycle and that he was able to keep his balance and not lay the bike down,” Sarasota County Deputy C. Moore wrote in his report. “The motorcycle was damaged on the right side near [his] foot, verifying his story. Both victims were adamant that the defendant actually and intentionally struck the motorcycle with his car due to the previous altercation.”

Dr. Maag told officers the motorcyclist had initiated the confrontation. He acknowledged racing after the biker, but said it was the motorcyclist who hit his vehicle. In an interview, Dr. Maag disputed the witnesses’ accounts, saying that one of the witnesses was without a car and made claims to police that were impossible from her distance. 

In the end, the officer believed the motorcyclist, writing in his report that the damage to the Tesla was consistent with the biker’s version of events. Dr. Maag was handcuffed and taken to the Sarasota County Jail.

“I was in shock,” he said. “When we got to the jail, they got me booked in and fingerprinted. I sat down and said [to an officer]: ‘So, when do I get to bond out?’ The guy started laughing and said: ‘You’re not going anywhere. You’re spending the night in jail, my friend.’ He said: ‘Your charge is one step below murder.’”
 

‘I like to drive fast’

Aside from speeding tickets, Dr. Maag said he had never been in serious trouble with the law before.

The husband and father of two has practiced emergency medicine for more 15 years, and his license has remained in good standing. Florida Department of Health records show Dr. Maag’s medical license as clear and active with no discipline cases or public complaints on file.

“I did my best for every patient that came through that door,” he said. “There were a lot of people who didn’t like my personality. I’ve said many times: ‘I’m not here to be liked. I’m here to take care of people and provide the best care possible.’ ” 

Sarasota County records show that Dr. Maag has received traffic citations in the past for careless driving, unlawful speed, and failure to stop at a red light, among others. He admits to having a “lead foot,” but says he had never before been involved in a road rage incident.

“I’m not going to lie, I like to drive fast,” he said. “I like that feeling. It just seems to slow everything down for me, the faster I’m going.”

After being booked into jail that July evening in 2015, Dr. Maag called his wife to explain what happened.

“She said, ‘I can’t believe you’ve done this. I’ve told you a million times, don’t worry about how other people drive. Keep your mouth shut,’” he recalled. “I asked her to call my work and let them know I wouldn’t be coming in the next day. Until that happened, I had never missed a day of work since becoming a physician.”

After an anxious night in his jail cell, Dr. Maag lined up with the other inmates the next morning for his bond hearing. His charges included felony, aggravated battery, and felony aggravated assault with a deadly weapon. A prosecutor recommended Dr. Maag’s bond be set at $1 million, which a judge lowered to $500,000.

Michael Fayard, a criminal defense attorney who represented Dr. Maag in the case, said even with the reduction, $500,000 was an outrageous bond for such a case.

“The prosecutor’s arguments to the judge were that he was a physician driving a Tesla,” Mr. Fayard said. “That was his exact argument for charging him a higher bond. It shouldn’t have been that high. I argued he was not a flight risk. He didn’t even have a passport.”

The Florida State Attorney’s Office did not return messages seeking comment about the case.

Dr. Maag spent 2 more nights in jail while he and his wife came up with $50,000 in cash, in accordance with the 10% bond rule. In the meantime, the government put a lien on their house. A circuit court judge later agreed the bond was excessive, according to Mr. Fayard, but by that time, the $50,000 was paid and Dr. Maag was released.
 

New evidence lowers charges 

Dr. Maag ultimately accepted a plea deal from the prosecutor’s office and pled no contest to one count of felony criminal mischief and one count of misdemeanor reckless driving. In return, the state dropped the two more serious felonies. A no-contest plea is not considered an admission of guilt.

Mr. Fayard said his investigation into the road rage victim unearthed evidence that poked holes in the motorcyclist’s credibility, and that contributed to the plea offer.

“We found tons of evidence about the kid being a hot-rodding rider on his motorcycle, videos of him traveling 140 miles an hour, popping wheelies, and darting in and out of traffic,” he said. “There was a lot of mitigation that came up during the course of the investigation.”

The plea deal was a favorable result for Dr. Maag considering his original charges, Mr. Fayard said. He added that the criminal case could have ended much differently.

“Given the facts of this case and given the fact that there were no serious injuries, we supported the state’s decision to accept our mitigation and come out with the sentence that they did,” Mr. Fayard said. “If there would have been injuries, the outcome would have likely been much worse for Dr. Maag.”

With the plea agreement reached, Dr. Maag faced his next consequence – jail time. He was sentenced to 60 days in jail, a $1,000 fine, 12 months of probation, and 8 months of house arrest. Unlike his first jail stay, Dr. Maag said the second, longer stint behind bars was more relaxing. 

“It was the first time since I had become an emergency physician that I remember my dreams,” he recalled. “I had nothing to worry about, nothing to do. All I had to do was get up and eat. Every now and then, I would mop the floors because I’m kind of a clean freak, and I would talk to guys and that was it. It wasn’t bad at all.”

Dr. Maag told no one that he was a doctor because he didn’t want to be treated differently. The anonymity led to interesting tidbits from other inmates about the best pill mills in the area for example, how to make crack cocaine, and selling items for drugs. On his last day in jail, the other inmates learned from his discharge paperwork that Dr. Maag was a physician.

“One of the corrections officers said: ‘You’re a doctor? We’ve never had a doctor in here before!’” Dr. Maag remembers. “He said: ‘What did a doctor do to get into jail?’ I said: ‘Do you really want to know?’ ”

About the time that Dr. Maag was released from jail, the Florida Board of Medicine learned of his charges and began reviewing his case. Mr. Fayard presented the same facts to the board and argued for Dr. Maag to keep his license, emphasizing the offenses in which he was convicted were significantly less severe than the original felonies charged. The board agreed to dismiss the case. 

“The probable cause panel for the board of medicine considered the complaint that has been filed against your client in the above referenced case,” Peter Delia, then-assistant general counsel for the Florida Department of Health, wrote in a letter dated April 27, 2016. “After careful review of all information and evidence obtained in this case, the panel determined that probable cause of a violation does not exist and directed this case to be closed.”
 

A short-lived celebration

Once home, Dr. Maag was on house arrest, but he was granted permission to travel for work. He continued to practice emergency medicine. After several months, authorities dropped the house arrest, and a judge canceled his probation early. It appeared the road rage incident was finally behind him. 

But a year later, in 2018, the doctor received a letter from the Centers for Medicare & Medicaid Services informing him that because of his charges, his Medicare number had been revoked in November 2015.

“It took them 3 years to find me and tell me, even though I never moved,” he said. “Medicare said because I never reported this, they were hitting me up with falsification of documentation because I had signed other Medicare paperwork saying I had never been barred from Medicare, because I didn’t know that I was.”

Dr. Maag hired a different attorney to help him fight the 3-year enrollment ban. He requested reconsideration from CMS, but a hearing officer in October 2017 upheld the revocation. Because his privileges had been revoked in 2015, Dr. Maag’s practice group had to return all money billed by Dr. Maag to Medicare over the 3-year period, which totaled about $190,000.

A CMS spokeswoman declined to comment about Dr. Maag’s case, referring a reporter for this news organization to an administrative law judge’s decision that summarizes the agency’s findings.

According to the summary, in separate reconsidered determinations, the CMS hearing officer concluded that the revocation was proper under section 424.535(a)(3). The regulation, enacted in 2011, allows CMS to revoke billing privileges if a provider was convicted of a federal or state felony within the preceding 10 years that the agency determines is detrimental to the Medicare program and its beneficiaries.

The hearing officer reasoned that Dr. Maag “had been convicted of a felony that is akin to assault and, even if it were not, his actions showed a reckless disregard for the safety of others.” She concluded also that CMS could appropriately revoke Dr. Maag’s Medicare enrollment because he did not report his felony conviction within 30 days as required.

Dr. Maag went through several phases of fighting the revocation, including an appeal to the Department of Health & Human Services Departmental Appeals Board. He argued that his plea was a no-contest plea, which is not considered an admission of guilt. Dr. Maag and his attorney provided CMS a 15-page paper about his background, education, career accomplishments, and patient care history. They emphasized that Dr. Maag had never harmed or threatened a patient, and that his offense had nothing to do with his practice.

In February 2021, Judge Carolyn Cozad Hughes, an administrative law judge with CMS, upheld the 3-year revocation. In her decision, she wrote that for purposes of revocation under CMS law, “convicted” means that a judgment of conviction has been entered by a federal, state, or local court regardless of whether the judgment of conviction has been expunged or otherwise removed. She disagreed with Dr. Maag’s contention that his was a crime against property and, therefore, not akin to any of the felony offenses enumerated under the revocation section, which are crimes against persons.

“Even disregarding the allegations contained in the probable cause affidavit, Petitioner cannot escape the undisputed fact, established by his conviction and his own admissions, that the ‘property’ he so ‘willfully and maliciously’ damaged was a motorcycle traveling at a high rate of speed, and, that two young people were sitting atop that motorcycle,” Judge Hughes wrote. “Moreover, as part of the same conduct, he was charged – and convicted – of misdemeanor reckless driving with ‘willful and wanton disregard for the safety of persons or property.’ Thus, even accepting Petitioner’s description of the events, he unquestionably showed no regard for the safety of the young people on that motorcycle.”

Judge Hughes noted that, although Dr. Maag’s crimes may not be among those specified in the regulation, CMS has broad authority to determine which felonies are detrimental to the best interests of the program and its beneficiaries.
 

A new career path

Unable to practice emergency medicine and beset with debt, Dr. Maag spiraled into a dark depression. His family had to start using retirement money that he was saving for the future care of his son, who has autism.

“I was suicidal,” he said. “There were two times that I came very close to going out to the woods by my house and hanging myself. All I wanted was to have everything go away. My wife saved my life.”

Slowly, Dr. Maag climbed out of the despondency and began considering new career options. After working and training briefly in hair restoration, Dr. Maag became a hair transplant specialist and opened his own hair restoration practice. It was a way to practice and help patients without having to accept Medicare. Today, he is the founder of Honest Hair Restoration in Bradenton, Fla.

Hair restoration is not the type of medicine that he “was designed to do,” Dr. Maag said, but he has embraced its advantages, such as learning about the business aspects of medicine and having a slower-paced work life. The business, which opened in 2019, is doing well and growing steadily.

Earlier this month, Dr. Maag learned CMS had reinstated his Medicare billing privileges. If an opportunity arises to go back into emergency medicine or urgent care, he is open to the possibilities, he said, but he plans to continue hair restoration for now. He hopes the lessons learned from his road rage incident may help others in similar circumstances.

“If I could go back to that very moment, I would’ve just kept my window up and I wouldn’t have said anything,” Dr. Maag said. “I would’ve kept my mouth shut and gone on about my day. Would I have loved it to have never happened? Yeah, and I’d probably be starting my retirement now. Am I stronger now? Well, I’m probably a hell of a lot wiser. But when all is said and done, I don’t want anybody feeling sorry for me. It was all my doing and I have to live with the consequences.”

Mr. Fayard, the attorney, says the case is a cautionary tale for doctors.

“No one is really above the law,” he said. “There aren’t two legal systems. You can’t just pay a little money and be done. At every level, serious charges have serious ramifications for everyone involved. Law enforcement and judges are not going to care of you’re a physician and you commit a crime. But physicians have a lot more on the line than many others. They can lose their ability to practice.”

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

It was a 95° F day in July 2015, and emergency physician Martin Maag, MD, was driving down Bee Ridge Road, a busy seven-lane thoroughfare in Sarasota, Fla., on his way home from a family dinner. To distance himself from a truck blowing black smoke, Dr. Maag says he had just passed some vehicles, when a motorcycle flew past him in the turning lane and the passenger flipped him off.

“I started laughing because I knew we were coming up to a red light,” said Dr. Maag. “When we pulled up to the light, I put my window down and said: ‘Hey, you ought to be a little more careful about who you’re flipping off! You never know who it might be and what they might do.’ ”

The female passenger cursed at Dr. Maag, and the two traded profanities. The male driver then told Dr. Maag: “Get out of the car, old man,” according to Dr. Maag. Fuming, Dr. Maag got out of his black Tesla, and the two men met in the middle of the street.

“As soon as I got close enough to see him, I could tell he really looked young,” Dr. Maag recalls. “I said: ‘You’re like 12 years old. I’m going to end up beating your ass and then I’m going to go to jail. Go get on your bike, and ride home to your mom.’ I don’t remember what he said to me, but I spun around and said: ‘If you want to act like a man, meet me up the street in a parking lot and let’s have at it like men.’ ”

The motorcyclist got back on his white Suzuki and sped off, and Dr. Maag followed. Both vehicles went racing down the road, swerving between cars, and reaching speeds of 100 miles per hour, Dr. Maag said. At one point, Dr. Maag says he drove in front of the motorcyclist to slow him down, and the motorcycle clipped the back of his car. No one was seriously hurt, but soon Dr. Maag was in the back of a police cruiser headed to jail.

Dr. Maag wishes he could take back his actions that summer day 6 years ago. Those few minutes of fury have had lasting effects on the doctor’s life. The incident resulted in criminal charges, a jail sentence, thousands of dollars in legal fees, and a 3-year departure from emergency medicine. Although Dr. Maag did not lose his medical license as a result of the incident, the physician’s Medicare billing privileges were suspended because of a federal provision that ties some felonies to enrollment revocations.

Dr. Maag, 61, shared his story with this news organization to warn other physicians about the wide-ranging career ramifications that can happen as a result of offenses unrelated to medicine. 

“Every doctor, every health professional needs to know that there are a lot of consequences that go with our actions outside of work,” he said. “In my situation, what happened had nothing to do with medicine, it had nothing to do with patients, it had nothing to do my professional demeanor. But yet it affected my entire career, and I lost the ability to practice emergency medicine for 3 years. Three years for any doctor is a long time. Three years for emergency medicine is a lifetime.”
 

The physician ends up in jail

After the collision, Dr. Maag pulled over in a parking lot and dialed 911. Several passing motorists did the same. It appeared the biker was trying to get away, and Dr. Maag was concerned about the damage to his Tesla, he said. 

When police arrived, they heard very different accounts of what happened. The motorcyclist and his girlfriend claimed Dr. Maag was the aggressor during the altercation, and that he deliberately tried to hit them with his vehicle. Two witnesses at the scene said they had watched Dr. Maag pursue the motorcycle in his vehicle, and that they believed he crossed into their lane intentionally to strike the motorcycle, according to police reports.

“[The motorcyclist] stated that the vehicle struck his right foot when it hit the motorcycle and that he was able to keep his balance and not lay the bike down,” Sarasota County Deputy C. Moore wrote in his report. “The motorcycle was damaged on the right side near [his] foot, verifying his story. Both victims were adamant that the defendant actually and intentionally struck the motorcycle with his car due to the previous altercation.”

Dr. Maag told officers the motorcyclist had initiated the confrontation. He acknowledged racing after the biker, but said it was the motorcyclist who hit his vehicle. In an interview, Dr. Maag disputed the witnesses’ accounts, saying that one of the witnesses was without a car and made claims to police that were impossible from her distance. 

In the end, the officer believed the motorcyclist, writing in his report that the damage to the Tesla was consistent with the biker’s version of events. Dr. Maag was handcuffed and taken to the Sarasota County Jail.

“I was in shock,” he said. “When we got to the jail, they got me booked in and fingerprinted. I sat down and said [to an officer]: ‘So, when do I get to bond out?’ The guy started laughing and said: ‘You’re not going anywhere. You’re spending the night in jail, my friend.’ He said: ‘Your charge is one step below murder.’”
 

‘I like to drive fast’

Aside from speeding tickets, Dr. Maag said he had never been in serious trouble with the law before.

The husband and father of two has practiced emergency medicine for more 15 years, and his license has remained in good standing. Florida Department of Health records show Dr. Maag’s medical license as clear and active with no discipline cases or public complaints on file.

“I did my best for every patient that came through that door,” he said. “There were a lot of people who didn’t like my personality. I’ve said many times: ‘I’m not here to be liked. I’m here to take care of people and provide the best care possible.’ ” 

Sarasota County records show that Dr. Maag has received traffic citations in the past for careless driving, unlawful speed, and failure to stop at a red light, among others. He admits to having a “lead foot,” but says he had never before been involved in a road rage incident.

“I’m not going to lie, I like to drive fast,” he said. “I like that feeling. It just seems to slow everything down for me, the faster I’m going.”

After being booked into jail that July evening in 2015, Dr. Maag called his wife to explain what happened.

“She said, ‘I can’t believe you’ve done this. I’ve told you a million times, don’t worry about how other people drive. Keep your mouth shut,’” he recalled. “I asked her to call my work and let them know I wouldn’t be coming in the next day. Until that happened, I had never missed a day of work since becoming a physician.”

After an anxious night in his jail cell, Dr. Maag lined up with the other inmates the next morning for his bond hearing. His charges included felony, aggravated battery, and felony aggravated assault with a deadly weapon. A prosecutor recommended Dr. Maag’s bond be set at $1 million, which a judge lowered to $500,000.

Michael Fayard, a criminal defense attorney who represented Dr. Maag in the case, said even with the reduction, $500,000 was an outrageous bond for such a case.

“The prosecutor’s arguments to the judge were that he was a physician driving a Tesla,” Mr. Fayard said. “That was his exact argument for charging him a higher bond. It shouldn’t have been that high. I argued he was not a flight risk. He didn’t even have a passport.”

The Florida State Attorney’s Office did not return messages seeking comment about the case.

Dr. Maag spent 2 more nights in jail while he and his wife came up with $50,000 in cash, in accordance with the 10% bond rule. In the meantime, the government put a lien on their house. A circuit court judge later agreed the bond was excessive, according to Mr. Fayard, but by that time, the $50,000 was paid and Dr. Maag was released.
 

New evidence lowers charges 

Dr. Maag ultimately accepted a plea deal from the prosecutor’s office and pled no contest to one count of felony criminal mischief and one count of misdemeanor reckless driving. In return, the state dropped the two more serious felonies. A no-contest plea is not considered an admission of guilt.

Mr. Fayard said his investigation into the road rage victim unearthed evidence that poked holes in the motorcyclist’s credibility, and that contributed to the plea offer.

“We found tons of evidence about the kid being a hot-rodding rider on his motorcycle, videos of him traveling 140 miles an hour, popping wheelies, and darting in and out of traffic,” he said. “There was a lot of mitigation that came up during the course of the investigation.”

The plea deal was a favorable result for Dr. Maag considering his original charges, Mr. Fayard said. He added that the criminal case could have ended much differently.

“Given the facts of this case and given the fact that there were no serious injuries, we supported the state’s decision to accept our mitigation and come out with the sentence that they did,” Mr. Fayard said. “If there would have been injuries, the outcome would have likely been much worse for Dr. Maag.”

With the plea agreement reached, Dr. Maag faced his next consequence – jail time. He was sentenced to 60 days in jail, a $1,000 fine, 12 months of probation, and 8 months of house arrest. Unlike his first jail stay, Dr. Maag said the second, longer stint behind bars was more relaxing. 

“It was the first time since I had become an emergency physician that I remember my dreams,” he recalled. “I had nothing to worry about, nothing to do. All I had to do was get up and eat. Every now and then, I would mop the floors because I’m kind of a clean freak, and I would talk to guys and that was it. It wasn’t bad at all.”

Dr. Maag told no one that he was a doctor because he didn’t want to be treated differently. The anonymity led to interesting tidbits from other inmates about the best pill mills in the area for example, how to make crack cocaine, and selling items for drugs. On his last day in jail, the other inmates learned from his discharge paperwork that Dr. Maag was a physician.

“One of the corrections officers said: ‘You’re a doctor? We’ve never had a doctor in here before!’” Dr. Maag remembers. “He said: ‘What did a doctor do to get into jail?’ I said: ‘Do you really want to know?’ ”

About the time that Dr. Maag was released from jail, the Florida Board of Medicine learned of his charges and began reviewing his case. Mr. Fayard presented the same facts to the board and argued for Dr. Maag to keep his license, emphasizing the offenses in which he was convicted were significantly less severe than the original felonies charged. The board agreed to dismiss the case. 

“The probable cause panel for the board of medicine considered the complaint that has been filed against your client in the above referenced case,” Peter Delia, then-assistant general counsel for the Florida Department of Health, wrote in a letter dated April 27, 2016. “After careful review of all information and evidence obtained in this case, the panel determined that probable cause of a violation does not exist and directed this case to be closed.”
 

A short-lived celebration

Once home, Dr. Maag was on house arrest, but he was granted permission to travel for work. He continued to practice emergency medicine. After several months, authorities dropped the house arrest, and a judge canceled his probation early. It appeared the road rage incident was finally behind him. 

But a year later, in 2018, the doctor received a letter from the Centers for Medicare & Medicaid Services informing him that because of his charges, his Medicare number had been revoked in November 2015.

“It took them 3 years to find me and tell me, even though I never moved,” he said. “Medicare said because I never reported this, they were hitting me up with falsification of documentation because I had signed other Medicare paperwork saying I had never been barred from Medicare, because I didn’t know that I was.”

Dr. Maag hired a different attorney to help him fight the 3-year enrollment ban. He requested reconsideration from CMS, but a hearing officer in October 2017 upheld the revocation. Because his privileges had been revoked in 2015, Dr. Maag’s practice group had to return all money billed by Dr. Maag to Medicare over the 3-year period, which totaled about $190,000.

A CMS spokeswoman declined to comment about Dr. Maag’s case, referring a reporter for this news organization to an administrative law judge’s decision that summarizes the agency’s findings.

According to the summary, in separate reconsidered determinations, the CMS hearing officer concluded that the revocation was proper under section 424.535(a)(3). The regulation, enacted in 2011, allows CMS to revoke billing privileges if a provider was convicted of a federal or state felony within the preceding 10 years that the agency determines is detrimental to the Medicare program and its beneficiaries.

The hearing officer reasoned that Dr. Maag “had been convicted of a felony that is akin to assault and, even if it were not, his actions showed a reckless disregard for the safety of others.” She concluded also that CMS could appropriately revoke Dr. Maag’s Medicare enrollment because he did not report his felony conviction within 30 days as required.

Dr. Maag went through several phases of fighting the revocation, including an appeal to the Department of Health & Human Services Departmental Appeals Board. He argued that his plea was a no-contest plea, which is not considered an admission of guilt. Dr. Maag and his attorney provided CMS a 15-page paper about his background, education, career accomplishments, and patient care history. They emphasized that Dr. Maag had never harmed or threatened a patient, and that his offense had nothing to do with his practice.

In February 2021, Judge Carolyn Cozad Hughes, an administrative law judge with CMS, upheld the 3-year revocation. In her decision, she wrote that for purposes of revocation under CMS law, “convicted” means that a judgment of conviction has been entered by a federal, state, or local court regardless of whether the judgment of conviction has been expunged or otherwise removed. She disagreed with Dr. Maag’s contention that his was a crime against property and, therefore, not akin to any of the felony offenses enumerated under the revocation section, which are crimes against persons.

“Even disregarding the allegations contained in the probable cause affidavit, Petitioner cannot escape the undisputed fact, established by his conviction and his own admissions, that the ‘property’ he so ‘willfully and maliciously’ damaged was a motorcycle traveling at a high rate of speed, and, that two young people were sitting atop that motorcycle,” Judge Hughes wrote. “Moreover, as part of the same conduct, he was charged – and convicted – of misdemeanor reckless driving with ‘willful and wanton disregard for the safety of persons or property.’ Thus, even accepting Petitioner’s description of the events, he unquestionably showed no regard for the safety of the young people on that motorcycle.”

Judge Hughes noted that, although Dr. Maag’s crimes may not be among those specified in the regulation, CMS has broad authority to determine which felonies are detrimental to the best interests of the program and its beneficiaries.
 

A new career path

Unable to practice emergency medicine and beset with debt, Dr. Maag spiraled into a dark depression. His family had to start using retirement money that he was saving for the future care of his son, who has autism.

“I was suicidal,” he said. “There were two times that I came very close to going out to the woods by my house and hanging myself. All I wanted was to have everything go away. My wife saved my life.”

Slowly, Dr. Maag climbed out of the despondency and began considering new career options. After working and training briefly in hair restoration, Dr. Maag became a hair transplant specialist and opened his own hair restoration practice. It was a way to practice and help patients without having to accept Medicare. Today, he is the founder of Honest Hair Restoration in Bradenton, Fla.

Hair restoration is not the type of medicine that he “was designed to do,” Dr. Maag said, but he has embraced its advantages, such as learning about the business aspects of medicine and having a slower-paced work life. The business, which opened in 2019, is doing well and growing steadily.

Earlier this month, Dr. Maag learned CMS had reinstated his Medicare billing privileges. If an opportunity arises to go back into emergency medicine or urgent care, he is open to the possibilities, he said, but he plans to continue hair restoration for now. He hopes the lessons learned from his road rage incident may help others in similar circumstances.

“If I could go back to that very moment, I would’ve just kept my window up and I wouldn’t have said anything,” Dr. Maag said. “I would’ve kept my mouth shut and gone on about my day. Would I have loved it to have never happened? Yeah, and I’d probably be starting my retirement now. Am I stronger now? Well, I’m probably a hell of a lot wiser. But when all is said and done, I don’t want anybody feeling sorry for me. It was all my doing and I have to live with the consequences.”

Mr. Fayard, the attorney, says the case is a cautionary tale for doctors.

“No one is really above the law,” he said. “There aren’t two legal systems. You can’t just pay a little money and be done. At every level, serious charges have serious ramifications for everyone involved. Law enforcement and judges are not going to care of you’re a physician and you commit a crime. But physicians have a lot more on the line than many others. They can lose their ability to practice.”

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

It was a 95° F day in July 2015, and emergency physician Martin Maag, MD, was driving down Bee Ridge Road, a busy seven-lane thoroughfare in Sarasota, Fla., on his way home from a family dinner. To distance himself from a truck blowing black smoke, Dr. Maag says he had just passed some vehicles, when a motorcycle flew past him in the turning lane and the passenger flipped him off.

“I started laughing because I knew we were coming up to a red light,” said Dr. Maag. “When we pulled up to the light, I put my window down and said: ‘Hey, you ought to be a little more careful about who you’re flipping off! You never know who it might be and what they might do.’ ”

The female passenger cursed at Dr. Maag, and the two traded profanities. The male driver then told Dr. Maag: “Get out of the car, old man,” according to Dr. Maag. Fuming, Dr. Maag got out of his black Tesla, and the two men met in the middle of the street.

“As soon as I got close enough to see him, I could tell he really looked young,” Dr. Maag recalls. “I said: ‘You’re like 12 years old. I’m going to end up beating your ass and then I’m going to go to jail. Go get on your bike, and ride home to your mom.’ I don’t remember what he said to me, but I spun around and said: ‘If you want to act like a man, meet me up the street in a parking lot and let’s have at it like men.’ ”

The motorcyclist got back on his white Suzuki and sped off, and Dr. Maag followed. Both vehicles went racing down the road, swerving between cars, and reaching speeds of 100 miles per hour, Dr. Maag said. At one point, Dr. Maag says he drove in front of the motorcyclist to slow him down, and the motorcycle clipped the back of his car. No one was seriously hurt, but soon Dr. Maag was in the back of a police cruiser headed to jail.

Dr. Maag wishes he could take back his actions that summer day 6 years ago. Those few minutes of fury have had lasting effects on the doctor’s life. The incident resulted in criminal charges, a jail sentence, thousands of dollars in legal fees, and a 3-year departure from emergency medicine. Although Dr. Maag did not lose his medical license as a result of the incident, the physician’s Medicare billing privileges were suspended because of a federal provision that ties some felonies to enrollment revocations.

Dr. Maag, 61, shared his story with this news organization to warn other physicians about the wide-ranging career ramifications that can happen as a result of offenses unrelated to medicine. 

“Every doctor, every health professional needs to know that there are a lot of consequences that go with our actions outside of work,” he said. “In my situation, what happened had nothing to do with medicine, it had nothing to do with patients, it had nothing to do my professional demeanor. But yet it affected my entire career, and I lost the ability to practice emergency medicine for 3 years. Three years for any doctor is a long time. Three years for emergency medicine is a lifetime.”
 

The physician ends up in jail

After the collision, Dr. Maag pulled over in a parking lot and dialed 911. Several passing motorists did the same. It appeared the biker was trying to get away, and Dr. Maag was concerned about the damage to his Tesla, he said. 

When police arrived, they heard very different accounts of what happened. The motorcyclist and his girlfriend claimed Dr. Maag was the aggressor during the altercation, and that he deliberately tried to hit them with his vehicle. Two witnesses at the scene said they had watched Dr. Maag pursue the motorcycle in his vehicle, and that they believed he crossed into their lane intentionally to strike the motorcycle, according to police reports.

“[The motorcyclist] stated that the vehicle struck his right foot when it hit the motorcycle and that he was able to keep his balance and not lay the bike down,” Sarasota County Deputy C. Moore wrote in his report. “The motorcycle was damaged on the right side near [his] foot, verifying his story. Both victims were adamant that the defendant actually and intentionally struck the motorcycle with his car due to the previous altercation.”

Dr. Maag told officers the motorcyclist had initiated the confrontation. He acknowledged racing after the biker, but said it was the motorcyclist who hit his vehicle. In an interview, Dr. Maag disputed the witnesses’ accounts, saying that one of the witnesses was without a car and made claims to police that were impossible from her distance. 

In the end, the officer believed the motorcyclist, writing in his report that the damage to the Tesla was consistent with the biker’s version of events. Dr. Maag was handcuffed and taken to the Sarasota County Jail.

“I was in shock,” he said. “When we got to the jail, they got me booked in and fingerprinted. I sat down and said [to an officer]: ‘So, when do I get to bond out?’ The guy started laughing and said: ‘You’re not going anywhere. You’re spending the night in jail, my friend.’ He said: ‘Your charge is one step below murder.’”
 

‘I like to drive fast’

Aside from speeding tickets, Dr. Maag said he had never been in serious trouble with the law before.

The husband and father of two has practiced emergency medicine for more 15 years, and his license has remained in good standing. Florida Department of Health records show Dr. Maag’s medical license as clear and active with no discipline cases or public complaints on file.

“I did my best for every patient that came through that door,” he said. “There were a lot of people who didn’t like my personality. I’ve said many times: ‘I’m not here to be liked. I’m here to take care of people and provide the best care possible.’ ” 

Sarasota County records show that Dr. Maag has received traffic citations in the past for careless driving, unlawful speed, and failure to stop at a red light, among others. He admits to having a “lead foot,” but says he had never before been involved in a road rage incident.

“I’m not going to lie, I like to drive fast,” he said. “I like that feeling. It just seems to slow everything down for me, the faster I’m going.”

After being booked into jail that July evening in 2015, Dr. Maag called his wife to explain what happened.

“She said, ‘I can’t believe you’ve done this. I’ve told you a million times, don’t worry about how other people drive. Keep your mouth shut,’” he recalled. “I asked her to call my work and let them know I wouldn’t be coming in the next day. Until that happened, I had never missed a day of work since becoming a physician.”

After an anxious night in his jail cell, Dr. Maag lined up with the other inmates the next morning for his bond hearing. His charges included felony, aggravated battery, and felony aggravated assault with a deadly weapon. A prosecutor recommended Dr. Maag’s bond be set at $1 million, which a judge lowered to $500,000.

Michael Fayard, a criminal defense attorney who represented Dr. Maag in the case, said even with the reduction, $500,000 was an outrageous bond for such a case.

“The prosecutor’s arguments to the judge were that he was a physician driving a Tesla,” Mr. Fayard said. “That was his exact argument for charging him a higher bond. It shouldn’t have been that high. I argued he was not a flight risk. He didn’t even have a passport.”

The Florida State Attorney’s Office did not return messages seeking comment about the case.

Dr. Maag spent 2 more nights in jail while he and his wife came up with $50,000 in cash, in accordance with the 10% bond rule. In the meantime, the government put a lien on their house. A circuit court judge later agreed the bond was excessive, according to Mr. Fayard, but by that time, the $50,000 was paid and Dr. Maag was released.
 

New evidence lowers charges 

Dr. Maag ultimately accepted a plea deal from the prosecutor’s office and pled no contest to one count of felony criminal mischief and one count of misdemeanor reckless driving. In return, the state dropped the two more serious felonies. A no-contest plea is not considered an admission of guilt.

Mr. Fayard said his investigation into the road rage victim unearthed evidence that poked holes in the motorcyclist’s credibility, and that contributed to the plea offer.

“We found tons of evidence about the kid being a hot-rodding rider on his motorcycle, videos of him traveling 140 miles an hour, popping wheelies, and darting in and out of traffic,” he said. “There was a lot of mitigation that came up during the course of the investigation.”

The plea deal was a favorable result for Dr. Maag considering his original charges, Mr. Fayard said. He added that the criminal case could have ended much differently.

“Given the facts of this case and given the fact that there were no serious injuries, we supported the state’s decision to accept our mitigation and come out with the sentence that they did,” Mr. Fayard said. “If there would have been injuries, the outcome would have likely been much worse for Dr. Maag.”

With the plea agreement reached, Dr. Maag faced his next consequence – jail time. He was sentenced to 60 days in jail, a $1,000 fine, 12 months of probation, and 8 months of house arrest. Unlike his first jail stay, Dr. Maag said the second, longer stint behind bars was more relaxing. 

“It was the first time since I had become an emergency physician that I remember my dreams,” he recalled. “I had nothing to worry about, nothing to do. All I had to do was get up and eat. Every now and then, I would mop the floors because I’m kind of a clean freak, and I would talk to guys and that was it. It wasn’t bad at all.”

Dr. Maag told no one that he was a doctor because he didn’t want to be treated differently. The anonymity led to interesting tidbits from other inmates about the best pill mills in the area for example, how to make crack cocaine, and selling items for drugs. On his last day in jail, the other inmates learned from his discharge paperwork that Dr. Maag was a physician.

“One of the corrections officers said: ‘You’re a doctor? We’ve never had a doctor in here before!’” Dr. Maag remembers. “He said: ‘What did a doctor do to get into jail?’ I said: ‘Do you really want to know?’ ”

About the time that Dr. Maag was released from jail, the Florida Board of Medicine learned of his charges and began reviewing his case. Mr. Fayard presented the same facts to the board and argued for Dr. Maag to keep his license, emphasizing the offenses in which he was convicted were significantly less severe than the original felonies charged. The board agreed to dismiss the case. 

“The probable cause panel for the board of medicine considered the complaint that has been filed against your client in the above referenced case,” Peter Delia, then-assistant general counsel for the Florida Department of Health, wrote in a letter dated April 27, 2016. “After careful review of all information and evidence obtained in this case, the panel determined that probable cause of a violation does not exist and directed this case to be closed.”
 

A short-lived celebration

Once home, Dr. Maag was on house arrest, but he was granted permission to travel for work. He continued to practice emergency medicine. After several months, authorities dropped the house arrest, and a judge canceled his probation early. It appeared the road rage incident was finally behind him. 

But a year later, in 2018, the doctor received a letter from the Centers for Medicare & Medicaid Services informing him that because of his charges, his Medicare number had been revoked in November 2015.

“It took them 3 years to find me and tell me, even though I never moved,” he said. “Medicare said because I never reported this, they were hitting me up with falsification of documentation because I had signed other Medicare paperwork saying I had never been barred from Medicare, because I didn’t know that I was.”

Dr. Maag hired a different attorney to help him fight the 3-year enrollment ban. He requested reconsideration from CMS, but a hearing officer in October 2017 upheld the revocation. Because his privileges had been revoked in 2015, Dr. Maag’s practice group had to return all money billed by Dr. Maag to Medicare over the 3-year period, which totaled about $190,000.

A CMS spokeswoman declined to comment about Dr. Maag’s case, referring a reporter for this news organization to an administrative law judge’s decision that summarizes the agency’s findings.

According to the summary, in separate reconsidered determinations, the CMS hearing officer concluded that the revocation was proper under section 424.535(a)(3). The regulation, enacted in 2011, allows CMS to revoke billing privileges if a provider was convicted of a federal or state felony within the preceding 10 years that the agency determines is detrimental to the Medicare program and its beneficiaries.

The hearing officer reasoned that Dr. Maag “had been convicted of a felony that is akin to assault and, even if it were not, his actions showed a reckless disregard for the safety of others.” She concluded also that CMS could appropriately revoke Dr. Maag’s Medicare enrollment because he did not report his felony conviction within 30 days as required.

Dr. Maag went through several phases of fighting the revocation, including an appeal to the Department of Health & Human Services Departmental Appeals Board. He argued that his plea was a no-contest plea, which is not considered an admission of guilt. Dr. Maag and his attorney provided CMS a 15-page paper about his background, education, career accomplishments, and patient care history. They emphasized that Dr. Maag had never harmed or threatened a patient, and that his offense had nothing to do with his practice.

In February 2021, Judge Carolyn Cozad Hughes, an administrative law judge with CMS, upheld the 3-year revocation. In her decision, she wrote that for purposes of revocation under CMS law, “convicted” means that a judgment of conviction has been entered by a federal, state, or local court regardless of whether the judgment of conviction has been expunged or otherwise removed. She disagreed with Dr. Maag’s contention that his was a crime against property and, therefore, not akin to any of the felony offenses enumerated under the revocation section, which are crimes against persons.

“Even disregarding the allegations contained in the probable cause affidavit, Petitioner cannot escape the undisputed fact, established by his conviction and his own admissions, that the ‘property’ he so ‘willfully and maliciously’ damaged was a motorcycle traveling at a high rate of speed, and, that two young people were sitting atop that motorcycle,” Judge Hughes wrote. “Moreover, as part of the same conduct, he was charged – and convicted – of misdemeanor reckless driving with ‘willful and wanton disregard for the safety of persons or property.’ Thus, even accepting Petitioner’s description of the events, he unquestionably showed no regard for the safety of the young people on that motorcycle.”

Judge Hughes noted that, although Dr. Maag’s crimes may not be among those specified in the regulation, CMS has broad authority to determine which felonies are detrimental to the best interests of the program and its beneficiaries.
 

A new career path

Unable to practice emergency medicine and beset with debt, Dr. Maag spiraled into a dark depression. His family had to start using retirement money that he was saving for the future care of his son, who has autism.

“I was suicidal,” he said. “There were two times that I came very close to going out to the woods by my house and hanging myself. All I wanted was to have everything go away. My wife saved my life.”

Slowly, Dr. Maag climbed out of the despondency and began considering new career options. After working and training briefly in hair restoration, Dr. Maag became a hair transplant specialist and opened his own hair restoration practice. It was a way to practice and help patients without having to accept Medicare. Today, he is the founder of Honest Hair Restoration in Bradenton, Fla.

Hair restoration is not the type of medicine that he “was designed to do,” Dr. Maag said, but he has embraced its advantages, such as learning about the business aspects of medicine and having a slower-paced work life. The business, which opened in 2019, is doing well and growing steadily.

Earlier this month, Dr. Maag learned CMS had reinstated his Medicare billing privileges. If an opportunity arises to go back into emergency medicine or urgent care, he is open to the possibilities, he said, but he plans to continue hair restoration for now. He hopes the lessons learned from his road rage incident may help others in similar circumstances.

“If I could go back to that very moment, I would’ve just kept my window up and I wouldn’t have said anything,” Dr. Maag said. “I would’ve kept my mouth shut and gone on about my day. Would I have loved it to have never happened? Yeah, and I’d probably be starting my retirement now. Am I stronger now? Well, I’m probably a hell of a lot wiser. But when all is said and done, I don’t want anybody feeling sorry for me. It was all my doing and I have to live with the consequences.”

Mr. Fayard, the attorney, says the case is a cautionary tale for doctors.

“No one is really above the law,” he said. “There aren’t two legal systems. You can’t just pay a little money and be done. At every level, serious charges have serious ramifications for everyone involved. Law enforcement and judges are not going to care of you’re a physician and you commit a crime. But physicians have a lot more on the line than many others. They can lose their ability to practice.”

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

Compared with their non-Black counterparts, Black patients with atopic dermatitis (AD) are significantly more likely to be younger, have lower household incomes, live in an urban setting, and use Medicaid or state assistance. They also have significantly poorer disease control and an increased rate of comorbid skin infections.

Those are among the key findings from a 25-question survey administered to members of the National Eczema Association.

“Black individuals with AD have a unique sociodemographic and disease profile,” lead study investigator Raj Chovatiya, MD, PhD, said during the Revolutionizing Atopic Dermatitis symposium. “Out-of-pocket expenses are just one component of the real-world burden faced by this population.”

According to Dr. Chovatiya, of the department of dermatology at Northwestern University, Chicago, the clinical phenotype and burden of AD can vary across racial and ethnic groups. Black race, for example, is associated with a higher prevalence of AD, a higher burden of moderate to severe disease, increased rates of allergic comorbidities, greater AD-related impact on health-related quality of life, and more treatment-resistant AD.

“These features can make long-term AD control very difficult,” he said. “Given the variable long-term efficacy and safety of current treatments, health care providers and patients often have to combine therapies, seek new treatments, and consider adjunctive approaches – all of which can contribute to increased costs.”

AD is also associated with a considerable financial burden, he continued, including direct health care costs, lost work productivity and out-of-pocket health care expenses. “Previous population-based studies suggest that there are multifactorial increases in overall out-of-pocket health expenses in AD,” Dr. Chovatiya said. “Black race in particular is thought to be associated with increased health care utilization in AD, but little is known about the out-of-pocket health care expenses.”

To characterize the categories and impact of out-of-pocket health care expenses associated with AD management among Black individuals, he and his colleagues administered a 25-question voluntary survey to 113,502 members of the NEA between Nov. 14 and Dec. 21, 2019. They included adults with a self-reported diagnosis of AD or children, teens, or young adults who had a caregiver responding for them. In all, 1,118 respondents met inclusion criteria. Questions included those about out-of-pocket expenses for AD over the past 30 days and over the past year, as well as the disease impact on household finances.

The cohort included 75% of individuals with AD; 25% were primary caregivers of children, teens, and young adults with AD. More than three-quarters of respondents (77%) were female, 73% were White, 11% were Black, 6% were Asian, and the remainder were from other ethnic backgrounds. More than half of respondents (58%) had employer-sponsored insurance coverage and the median annual household income was between $50,000 and $75,000.

Nearly three-quarters of respondents (74%) classified their AD severity as moderate or severe, and 63% reported minimally controlled or somewhat-controlled AD. Black respondents were significantly more likely to be younger, have lower household incomes, live in an urban setting, use Medicaid or state assistance, have poor disease control, and frequent skin infections (P ≤ .02). “A numerically higher proportion of Black respondents also had increased AD severity and reported the use of step-up therapy with systemic agents, prescription polypharmacy with three or more prescriptions, and a higher monthly out-of-pocket cost,” Dr. Chovatiya said.

Compared with their non-Black counterparts, Black survey respondents reported more out-of-pocket costs for prescription medications covered by insurance (74.2% vs. 63.6%, P = .04), prescription medications not covered by insurance (65.1% vs. 46.5%, P = .0004), ED visits (22.1% vs. 11.8%, P = .005), and outpatient laboratory testing (33.3% vs. 21.8%, P = .01). Black race was associated with increased household financial impact from out-of-pocket expenses (P = .0009), and predictors of financial impact included minimally controlled AD (adjusted odds ratio, 13.88; P = .02), comorbid anxiety and/or depression (aOR, 4.34; P = .01), systemic therapy (aOR, 4.34; P = .003), out-of-pocket costs that exceeded $200 per month (aOR, 14.28; P = .0003), and Medicaid insurance (aOR, 4.02; P = .03). Blacks with Medicaid had higher odds of harmful financial impact (aOR, 3.32; P = .0002) than respondents who were Black (aOR, 1.81; P = .04) or those with Medicaid alone (aOR, 1.39; P = .04).

“I looked at some of the findings from recent studies that have talked about this burden, including an increased prevalence among Black children, a higher likelihood of moderate to severe disease, higher rates of ED visits and hospitalizations, and increased prescription medications,” Dr. Chovatiya said.“Our findings reflect these racial and socioeconomic disparities and provide another piece of evidence for increased financial burden among Black individuals with AD and support the need for targeted strategies to address these inequities.”

The study received funding support from the NEA. Dr. Chovatiya disclosed that he is a consultant to, a speaker for, and/or a member of the advisory board for AbbVie, Incyte, and Regeneron/Sanofi-Genzyme.

[email protected]

Compared with their non-Black counterparts, Black patients with atopic dermatitis (AD) are significantly more likely to be younger, have lower household incomes, live in an urban setting, and use Medicaid or state assistance. They also have significantly poorer disease control and an increased rate of comorbid skin infections.

Those are among the key findings from a 25-question survey administered to members of the National Eczema Association.

“Black individuals with AD have a unique sociodemographic and disease profile,” lead study investigator Raj Chovatiya, MD, PhD, said during the Revolutionizing Atopic Dermatitis symposium. “Out-of-pocket expenses are just one component of the real-world burden faced by this population.”

According to Dr. Chovatiya, of the department of dermatology at Northwestern University, Chicago, the clinical phenotype and burden of AD can vary across racial and ethnic groups. Black race, for example, is associated with a higher prevalence of AD, a higher burden of moderate to severe disease, increased rates of allergic comorbidities, greater AD-related impact on health-related quality of life, and more treatment-resistant AD.

“These features can make long-term AD control very difficult,” he said. “Given the variable long-term efficacy and safety of current treatments, health care providers and patients often have to combine therapies, seek new treatments, and consider adjunctive approaches – all of which can contribute to increased costs.”

AD is also associated with a considerable financial burden, he continued, including direct health care costs, lost work productivity and out-of-pocket health care expenses. “Previous population-based studies suggest that there are multifactorial increases in overall out-of-pocket health expenses in AD,” Dr. Chovatiya said. “Black race in particular is thought to be associated with increased health care utilization in AD, but little is known about the out-of-pocket health care expenses.”

To characterize the categories and impact of out-of-pocket health care expenses associated with AD management among Black individuals, he and his colleagues administered a 25-question voluntary survey to 113,502 members of the NEA between Nov. 14 and Dec. 21, 2019. They included adults with a self-reported diagnosis of AD or children, teens, or young adults who had a caregiver responding for them. In all, 1,118 respondents met inclusion criteria. Questions included those about out-of-pocket expenses for AD over the past 30 days and over the past year, as well as the disease impact on household finances.

The cohort included 75% of individuals with AD; 25% were primary caregivers of children, teens, and young adults with AD. More than three-quarters of respondents (77%) were female, 73% were White, 11% were Black, 6% were Asian, and the remainder were from other ethnic backgrounds. More than half of respondents (58%) had employer-sponsored insurance coverage and the median annual household income was between $50,000 and $75,000.

Nearly three-quarters of respondents (74%) classified their AD severity as moderate or severe, and 63% reported minimally controlled or somewhat-controlled AD. Black respondents were significantly more likely to be younger, have lower household incomes, live in an urban setting, use Medicaid or state assistance, have poor disease control, and frequent skin infections (P ≤ .02). “A numerically higher proportion of Black respondents also had increased AD severity and reported the use of step-up therapy with systemic agents, prescription polypharmacy with three or more prescriptions, and a higher monthly out-of-pocket cost,” Dr. Chovatiya said.

Compared with their non-Black counterparts, Black survey respondents reported more out-of-pocket costs for prescription medications covered by insurance (74.2% vs. 63.6%, P = .04), prescription medications not covered by insurance (65.1% vs. 46.5%, P = .0004), ED visits (22.1% vs. 11.8%, P = .005), and outpatient laboratory testing (33.3% vs. 21.8%, P = .01). Black race was associated with increased household financial impact from out-of-pocket expenses (P = .0009), and predictors of financial impact included minimally controlled AD (adjusted odds ratio, 13.88; P = .02), comorbid anxiety and/or depression (aOR, 4.34; P = .01), systemic therapy (aOR, 4.34; P = .003), out-of-pocket costs that exceeded $200 per month (aOR, 14.28; P = .0003), and Medicaid insurance (aOR, 4.02; P = .03). Blacks with Medicaid had higher odds of harmful financial impact (aOR, 3.32; P = .0002) than respondents who were Black (aOR, 1.81; P = .04) or those with Medicaid alone (aOR, 1.39; P = .04).

“I looked at some of the findings from recent studies that have talked about this burden, including an increased prevalence among Black children, a higher likelihood of moderate to severe disease, higher rates of ED visits and hospitalizations, and increased prescription medications,” Dr. Chovatiya said.“Our findings reflect these racial and socioeconomic disparities and provide another piece of evidence for increased financial burden among Black individuals with AD and support the need for targeted strategies to address these inequities.”

The study received funding support from the NEA. Dr. Chovatiya disclosed that he is a consultant to, a speaker for, and/or a member of the advisory board for AbbVie, Incyte, and Regeneron/Sanofi-Genzyme.

[email protected]

Compared with their non-Black counterparts, Black patients with atopic dermatitis (AD) are significantly more likely to be younger, have lower household incomes, live in an urban setting, and use Medicaid or state assistance. They also have significantly poorer disease control and an increased rate of comorbid skin infections.

Those are among the key findings from a 25-question survey administered to members of the National Eczema Association.

“Black individuals with AD have a unique sociodemographic and disease profile,” lead study investigator Raj Chovatiya, MD, PhD, said during the Revolutionizing Atopic Dermatitis symposium. “Out-of-pocket expenses are just one component of the real-world burden faced by this population.”

According to Dr. Chovatiya, of the department of dermatology at Northwestern University, Chicago, the clinical phenotype and burden of AD can vary across racial and ethnic groups. Black race, for example, is associated with a higher prevalence of AD, a higher burden of moderate to severe disease, increased rates of allergic comorbidities, greater AD-related impact on health-related quality of life, and more treatment-resistant AD.

“These features can make long-term AD control very difficult,” he said. “Given the variable long-term efficacy and safety of current treatments, health care providers and patients often have to combine therapies, seek new treatments, and consider adjunctive approaches – all of which can contribute to increased costs.”

AD is also associated with a considerable financial burden, he continued, including direct health care costs, lost work productivity and out-of-pocket health care expenses. “Previous population-based studies suggest that there are multifactorial increases in overall out-of-pocket health expenses in AD,” Dr. Chovatiya said. “Black race in particular is thought to be associated with increased health care utilization in AD, but little is known about the out-of-pocket health care expenses.”

To characterize the categories and impact of out-of-pocket health care expenses associated with AD management among Black individuals, he and his colleagues administered a 25-question voluntary survey to 113,502 members of the NEA between Nov. 14 and Dec. 21, 2019. They included adults with a self-reported diagnosis of AD or children, teens, or young adults who had a caregiver responding for them. In all, 1,118 respondents met inclusion criteria. Questions included those about out-of-pocket expenses for AD over the past 30 days and over the past year, as well as the disease impact on household finances.

The cohort included 75% of individuals with AD; 25% were primary caregivers of children, teens, and young adults with AD. More than three-quarters of respondents (77%) were female, 73% were White, 11% were Black, 6% were Asian, and the remainder were from other ethnic backgrounds. More than half of respondents (58%) had employer-sponsored insurance coverage and the median annual household income was between $50,000 and $75,000.

Nearly three-quarters of respondents (74%) classified their AD severity as moderate or severe, and 63% reported minimally controlled or somewhat-controlled AD. Black respondents were significantly more likely to be younger, have lower household incomes, live in an urban setting, use Medicaid or state assistance, have poor disease control, and frequent skin infections (P ≤ .02). “A numerically higher proportion of Black respondents also had increased AD severity and reported the use of step-up therapy with systemic agents, prescription polypharmacy with three or more prescriptions, and a higher monthly out-of-pocket cost,” Dr. Chovatiya said.

Compared with their non-Black counterparts, Black survey respondents reported more out-of-pocket costs for prescription medications covered by insurance (74.2% vs. 63.6%, P = .04), prescription medications not covered by insurance (65.1% vs. 46.5%, P = .0004), ED visits (22.1% vs. 11.8%, P = .005), and outpatient laboratory testing (33.3% vs. 21.8%, P = .01). Black race was associated with increased household financial impact from out-of-pocket expenses (P = .0009), and predictors of financial impact included minimally controlled AD (adjusted odds ratio, 13.88; P = .02), comorbid anxiety and/or depression (aOR, 4.34; P = .01), systemic therapy (aOR, 4.34; P = .003), out-of-pocket costs that exceeded $200 per month (aOR, 14.28; P = .0003), and Medicaid insurance (aOR, 4.02; P = .03). Blacks with Medicaid had higher odds of harmful financial impact (aOR, 3.32; P = .0002) than respondents who were Black (aOR, 1.81; P = .04) or those with Medicaid alone (aOR, 1.39; P = .04).

“I looked at some of the findings from recent studies that have talked about this burden, including an increased prevalence among Black children, a higher likelihood of moderate to severe disease, higher rates of ED visits and hospitalizations, and increased prescription medications,” Dr. Chovatiya said.“Our findings reflect these racial and socioeconomic disparities and provide another piece of evidence for increased financial burden among Black individuals with AD and support the need for targeted strategies to address these inequities.”

The study received funding support from the NEA. Dr. Chovatiya disclosed that he is a consultant to, a speaker for, and/or a member of the advisory board for AbbVie, Incyte, and Regeneron/Sanofi-Genzyme.

[email protected]

In May 2020, two major scientific journals published and subsequently retracted studies that relied on data provided by the now-disgraced data analytics company Surgisphere.

One of the studies, published in The Lancet, reported an association between the antimalarial drugs hydroxychloroquine and chloroquine and increased in-hospital mortality and cardiac arrhythmias in patients with COVID-19. The second study, which appeared in the New England Journal of Medicine, described an association between underlying cardiovascular disease, but not related drug therapy, with increased mortality in COVID-19 patients.

The retractions in June 2020 followed an open letter to each publication penned by scientists, ethicists, and clinicians who flagged serious methodological and ethical anomalies in the data used in the studies.

On the 1-year anniversary, researchers and journal editors spoke about what was learned to reduce the risk of something like this happening again.

“The Surgisphere incident served as a wake-up call for everyone involved with scientific research to make sure that data have integrity and are robust,” Sunil Rao, MD, professor of medicine, Duke University Health System, Durham, N.C., and editor-in-chief of Circulation: Cardiovascular Interventions, said in an interview.

“I’m sure this isn’t going to be the last incident of this nature, and we have to be vigilant about new datasets or datasets that we haven’t heard of as having a track record of publication,” Dr. Rao said.
 

Spotlight on authors

The editors of the Lancet Group responded to the “wake-up call” with a statement, Learning From a Retraction, which announced changes to reduce the risks of research and publication misconduct.

The changes affect multiple phases of the publication process. For example, the declaration form that authors must sign “will require that more than one author has directly accessed and verified the data reported in the manuscript.” Additionally, when a research article is the result of an academic and commercial partnership – as was the case in the two retracted studies – “one of the authors named as having accessed and verified data must be from the academic team.”

This was particularly important because it appears that the academic coauthors of the retracted studies did not have access to the data provided by Surgisphere, a private commercial entity.

Mandeep R. Mehra, MD, William Harvey Distinguished Chair in Advanced Cardiovascular Medicine, Brigham and Women’s Hospital, Boston, who was the lead author of both studies, declined to be interviewed for this article. In a letter to the New England Journal of Medicine editors requesting that the article be retracted, he wrote: “Because all the authors were not granted access to the raw data and the raw data could not be made available to a third-party auditor, we are unable to validate the primary data sources underlying our article.”

In a similar communication with The Lancet, Dr. Mehra wrote even more pointedly that, in light of the refusal of Surgisphere to make the data available to the third-party auditor, “we can no longer vouch for the veracity of the primary data sources.”

“It is very disturbing that the authors were willing to put their names on a paper without ever seeing and verifying the data,” Mario Malički, MD, PhD, a postdoctoral researcher at METRICS at Stanford (Calif.) University, said in an interview. “Saying that they could ‘no longer vouch’ suggests that at one point they could vouch for it. Most likely they took its existence and veracity entirely on trust.”

Dr. Malički pointed out that one of the four criteria of the International Committee of Medical Journal Editors for being an author on a study is the “agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.”

The new policies put forth by The Lancet are “encouraging,” but perhaps do not go far enough. “Every author, not only one or two authors, should personally take responsibility for the integrity of data,” he stated.

Many journals “adhere to ICMJE rules in principle and have checkboxes for authors to confirm that they guarantee the veracity of the data.” However, they “do not have the resources to verify the authors’ statements.”

Ideally, “it is the institutions where the researchers work that should guarantee the veracity of the raw data – but I do not know any university or institute that does this,” he said.
 

No ‘good-housekeeping’ seal

For articles based on large, real-world datasets, the Lancet Group will now require that editors ensure that at least one peer reviewer is “knowledgeable about the details of the dataset being reported and can understand its strengths and limitations in relation to the question being addressed.”

For studies that use “very large datasets,” the editors are now required to ensure that, in addition to a statistical peer review, a review from an “expert in data science” is obtained. Reviewers will also be explicitly asked if they have “concerns about research integrity or publication ethics regarding the manuscript they are reviewing.”

Although these changes are encouraging, Harlan Krumholz, MD, professor of medicine (cardiology), Yale University, New Haven, Conn., is not convinced that they are realistic.

Dr. Krumholz, who is also the founder and director of the Yale New Haven Hospital Center for Outcome Research and Evaluation, said in an interview that “large, real-world datasets” are of two varieties. Datasets drawn from publicly available sources, such as Medicare or Medicaid health records, are utterly transparent.

By contrast, Surgisphere was a privately owned database, and “it is not unusual for privately owned databases to have proprietary data from multiple sources that the company may choose to keep confidential,” Dr. Krumholz said.

He noted that several large datasets are widely used for research purposes, such as IBM, Optum, and Komodo – a data analytics company that recently entered into partnership with a fourth company, PicnicHealth.

These companies receive deidentified electronic health records from health systems and insurers nationwide. Komodo boasts “real-time and longitudinal data on more than 325 million patients, representing more than 65 billion clinical encounters with 15 million new encounters added daily.”

“One has to raise an eyebrow – how were these data acquired? And, given that the U.S. has a population of around 328 million people, is it really plausible that a single company has health records of almost the entire U.S. population?” Dr. Krumholz commented. (A spokesperson for Komodo said in an interview that the company has records on 325 million U.S. patients.)

This is “an issue across the board with ‘real-world evidence,’ which is that it’s like the ‘Wild West’ – the transparencies of private databases are less than optimal and there are no common standards to help us move forward,” Dr. Krumholz said, noting that there is “no external authority overseeing, validating, or auditing these databases. In the end, we are trusting the companies.”

Although the Food and Drug Administration has laid out a framework for how real-world data and real-world evidence can be used to advance scientific research, the FDA does not oversee the databases.

“Thus, there is no ‘good housekeeping seal’ that a peer reviewer or author would be in a position to evaluate,” Dr. Krumholz said. “No journal can do an audit of these types of private databases, so ultimately, it boils down to trust.”

Nevertheless, there were red flags with Surgisphere, Dr. Rao pointed out. Unlike more established and widely used databases, the Surgisphere database had been catapulted from relative obscurity onto center stage, which should have given researchers pause.
 

AI-assisted peer review

A series of investigative reports by The Guardian raised questions about Sapan Desai, the CEO of Surgisphere, including the fact that hospitals purporting to have contributed data to Surgisphere had never heard of the company.

However, peer reviewers are not expected to be investigative reporters, explained Dr. Malički.

“In an ideal world, editors and peer reviewers would have a chance to look at raw data or would have a certificate from the academic institution the authors are affiliated with that the data have been inspected by the institution, but in the real world, of course, this does not happen,” he said.

Artificial intelligence software is being developed and deployed to assist in the peer review process, Dr. Malički noted. In July 2020, Frontiers Science News debuted its Artificial Intelligence Review Assistant to help editors, reviewers, and authors evaluate the quality of a manuscript. The program can make up to 20 recommendations, including “the assessment of language quality, the detection of plagiarism, and identification of potential conflicts of interest.” The program is now in use in all 103 journals published by Frontiers. Preliminary software is also available to detect statistical errors.

Another system under development is FAIRware, an initiative of the Research on Research Institute in partnership with the Stanford Center for Biomedical Informatics Research. The partnership’s goal is to “develop an automated online tool (or suite of tools) to help researchers ensure that the datasets they produce are ‘FAIR’ at the point of creation,” said Dr. Malički, referring to the findability, accessibility, interoperability, and reusability (FAIR) guiding principles for data management. The principles aim to increase the ability of machines to automatically find and use the data, as well as to support its reuse by individuals.

He added that these advanced tools cannot replace human reviewers, who will “likely always be a necessary quality check in the process.”
 

Greater transparency needed

Another limitation of peer review is the reviewers themselves, according to Dr. Malički. “It’s a step in the right direction that The Lancet is now requesting a peer reviewer with expertise in big datasets, but it does not go far enough to increase accountability of peer reviewers,” he said.

Dr. Malički is the co–editor-in-chief of the journal Research Integrity and Peer Review , which has “an open and transparent review process – meaning that we reveal the names of the reviewers to the public and we publish the full review report alongside the paper.” The publication also allows the authors to make public the original version they sent.

Dr. Malički cited several advantages to transparent peer review, particularly the increased accountability that results from placing potential conflicts of interest under the microscope.

As for the concern that identifying the reviewers might soften the review process, “there is little evidence to substantiate that concern,” he added.

Dr. Malički emphasized that making reviews public “is not a problem – people voice strong opinions at conferences and elsewhere. The question remains, who gets to decide if the criticism has been adequately addressed, so that the findings of the study still stand?”

He acknowledged that, “as in politics and on many social platforms, rage, hatred, and personal attacks divert the discussion from the topic at hand, which is why a good moderator is needed.”

A journal editor or a moderator at a scientific conference may be tasked with “stopping all talk not directly related to the topic.”
 

Widening the circle of scrutiny

Dr. Malički added: “A published paper should not be considered the ‘final word,’ even if it has gone through peer review and is published in a reputable journal. The peer-review process means that a limited number of people have seen the study.”

Once the study is published, “the whole world gets to see it and criticize it, and that widens the circle of scrutiny.”

One classic way to raise concerns about a study post publication is to write a letter to the journal editor. But there is no guarantee that the letter will be published or the authors notified of the feedback.

Dr. Malički encourages readers to use PubPeer, an online forum in which members of the public can post comments on scientific studies and articles.

Once a comment is posted, the authors are alerted. “There is no ‘police department’ that forces authors to acknowledge comments or forces journal editors to take action, but at least PubPeer guarantees that readers’ messages will reach the authors and – depending on how many people raise similar issues – the comments can lead to errata or even full retractions,” he said.

PubPeer was key in pointing out errors in a suspect study from France (which did not involve Surgisphere) that supported the use of hydroxychloroquine in COVID-19.
 

A message to policy makers

High stakes are involved in ensuring the integrity of scientific publications: The French government revoked a decree that allowed hospitals to prescribe hydroxychloroquine for certain COVID-19 patients.

After the Surgisphere Lancet article, the World Health Organization temporarily halted enrollment in the hydroxychloroquine component of the Solidarity international randomized trial of medications to treat COVID-19.

Similarly, the U.K. Medicines and Healthcare Products Regulatory Agency instructed the organizers of COPCOV, an international trial of the use of hydroxychloroquine as prophylaxis against COVID-19, to suspend recruitment of patients. The SOLIDARITY trial briefly resumed, but that arm of the trial was ultimately suspended after a preliminary analysis suggested that hydroxychloroquine provided no benefit for patients with COVID-19.

Dr. Malički emphasized that governments and organizations should not “blindly trust journal articles” and make policy decisions based exclusively on study findings in published journals – even with the current improvements in the peer review process – without having their own experts conduct a thorough review of the data.

“If you are not willing to do your own due diligence, then at least be brave enough and say transparently why you are making this policy, or any other changes, and clearly state if your decision is based primarily or solely on the fact that ‘X’ study was published in ‘Y’ journal,” he stated.

Dr. Rao believes that the most important take-home message of the Surgisphere scandal is “that we should be skeptical and do our own due diligence about the kinds of data published – a responsibility that applies to all of us, whether we are investigators, editors at journals, the press, scientists, and readers.”

Dr. Rao reported being on the steering committee of the National Heart, Lung, and Blood Institute–sponsored MINT trial and the Bayer-sponsored PACIFIC AMI trial. Dr. Malički reports being a postdoc at METRICS Stanford in the past 3 years. Dr. Krumholz received expenses and/or personal fees from UnitedHealth, Element Science, Aetna, Facebook, the Siegfried and Jensen Law Firm, Arnold and Porter Law Firm, Martin/Baughman Law Firm, F-Prime, and the National Center for Cardiovascular Diseases in Beijing. He is an owner of Refactor Health and HugoHealth and had grants and/or contracts from the Centers for Medicare & Medicaid Services, the FDA, Johnson & Johnson, and the Shenzhen Center for Health Information.

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

In May 2020, two major scientific journals published and subsequently retracted studies that relied on data provided by the now-disgraced data analytics company Surgisphere.

One of the studies, published in The Lancet, reported an association between the antimalarial drugs hydroxychloroquine and chloroquine and increased in-hospital mortality and cardiac arrhythmias in patients with COVID-19. The second study, which appeared in the New England Journal of Medicine, described an association between underlying cardiovascular disease, but not related drug therapy, with increased mortality in COVID-19 patients.

The retractions in June 2020 followed an open letter to each publication penned by scientists, ethicists, and clinicians who flagged serious methodological and ethical anomalies in the data used in the studies.

On the 1-year anniversary, researchers and journal editors spoke about what was learned to reduce the risk of something like this happening again.

“The Surgisphere incident served as a wake-up call for everyone involved with scientific research to make sure that data have integrity and are robust,” Sunil Rao, MD, professor of medicine, Duke University Health System, Durham, N.C., and editor-in-chief of Circulation: Cardiovascular Interventions, said in an interview.

“I’m sure this isn’t going to be the last incident of this nature, and we have to be vigilant about new datasets or datasets that we haven’t heard of as having a track record of publication,” Dr. Rao said.
 

Spotlight on authors

The editors of the Lancet Group responded to the “wake-up call” with a statement, Learning From a Retraction, which announced changes to reduce the risks of research and publication misconduct.

The changes affect multiple phases of the publication process. For example, the declaration form that authors must sign “will require that more than one author has directly accessed and verified the data reported in the manuscript.” Additionally, when a research article is the result of an academic and commercial partnership – as was the case in the two retracted studies – “one of the authors named as having accessed and verified data must be from the academic team.”

This was particularly important because it appears that the academic coauthors of the retracted studies did not have access to the data provided by Surgisphere, a private commercial entity.

Mandeep R. Mehra, MD, William Harvey Distinguished Chair in Advanced Cardiovascular Medicine, Brigham and Women’s Hospital, Boston, who was the lead author of both studies, declined to be interviewed for this article. In a letter to the New England Journal of Medicine editors requesting that the article be retracted, he wrote: “Because all the authors were not granted access to the raw data and the raw data could not be made available to a third-party auditor, we are unable to validate the primary data sources underlying our article.”

In a similar communication with The Lancet, Dr. Mehra wrote even more pointedly that, in light of the refusal of Surgisphere to make the data available to the third-party auditor, “we can no longer vouch for the veracity of the primary data sources.”

“It is very disturbing that the authors were willing to put their names on a paper without ever seeing and verifying the data,” Mario Malički, MD, PhD, a postdoctoral researcher at METRICS at Stanford (Calif.) University, said in an interview. “Saying that they could ‘no longer vouch’ suggests that at one point they could vouch for it. Most likely they took its existence and veracity entirely on trust.”

Dr. Malički pointed out that one of the four criteria of the International Committee of Medical Journal Editors for being an author on a study is the “agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.”

The new policies put forth by The Lancet are “encouraging,” but perhaps do not go far enough. “Every author, not only one or two authors, should personally take responsibility for the integrity of data,” he stated.

Many journals “adhere to ICMJE rules in principle and have checkboxes for authors to confirm that they guarantee the veracity of the data.” However, they “do not have the resources to verify the authors’ statements.”

Ideally, “it is the institutions where the researchers work that should guarantee the veracity of the raw data – but I do not know any university or institute that does this,” he said.
 

No ‘good-housekeeping’ seal

For articles based on large, real-world datasets, the Lancet Group will now require that editors ensure that at least one peer reviewer is “knowledgeable about the details of the dataset being reported and can understand its strengths and limitations in relation to the question being addressed.”

For studies that use “very large datasets,” the editors are now required to ensure that, in addition to a statistical peer review, a review from an “expert in data science” is obtained. Reviewers will also be explicitly asked if they have “concerns about research integrity or publication ethics regarding the manuscript they are reviewing.”

Although these changes are encouraging, Harlan Krumholz, MD, professor of medicine (cardiology), Yale University, New Haven, Conn., is not convinced that they are realistic.

Dr. Krumholz, who is also the founder and director of the Yale New Haven Hospital Center for Outcome Research and Evaluation, said in an interview that “large, real-world datasets” are of two varieties. Datasets drawn from publicly available sources, such as Medicare or Medicaid health records, are utterly transparent.

By contrast, Surgisphere was a privately owned database, and “it is not unusual for privately owned databases to have proprietary data from multiple sources that the company may choose to keep confidential,” Dr. Krumholz said.

He noted that several large datasets are widely used for research purposes, such as IBM, Optum, and Komodo – a data analytics company that recently entered into partnership with a fourth company, PicnicHealth.

These companies receive deidentified electronic health records from health systems and insurers nationwide. Komodo boasts “real-time and longitudinal data on more than 325 million patients, representing more than 65 billion clinical encounters with 15 million new encounters added daily.”

“One has to raise an eyebrow – how were these data acquired? And, given that the U.S. has a population of around 328 million people, is it really plausible that a single company has health records of almost the entire U.S. population?” Dr. Krumholz commented. (A spokesperson for Komodo said in an interview that the company has records on 325 million U.S. patients.)

This is “an issue across the board with ‘real-world evidence,’ which is that it’s like the ‘Wild West’ – the transparencies of private databases are less than optimal and there are no common standards to help us move forward,” Dr. Krumholz said, noting that there is “no external authority overseeing, validating, or auditing these databases. In the end, we are trusting the companies.”

Although the Food and Drug Administration has laid out a framework for how real-world data and real-world evidence can be used to advance scientific research, the FDA does not oversee the databases.

“Thus, there is no ‘good housekeeping seal’ that a peer reviewer or author would be in a position to evaluate,” Dr. Krumholz said. “No journal can do an audit of these types of private databases, so ultimately, it boils down to trust.”

Nevertheless, there were red flags with Surgisphere, Dr. Rao pointed out. Unlike more established and widely used databases, the Surgisphere database had been catapulted from relative obscurity onto center stage, which should have given researchers pause.
 

AI-assisted peer review

A series of investigative reports by The Guardian raised questions about Sapan Desai, the CEO of Surgisphere, including the fact that hospitals purporting to have contributed data to Surgisphere had never heard of the company.

However, peer reviewers are not expected to be investigative reporters, explained Dr. Malički.

“In an ideal world, editors and peer reviewers would have a chance to look at raw data or would have a certificate from the academic institution the authors are affiliated with that the data have been inspected by the institution, but in the real world, of course, this does not happen,” he said.

Artificial intelligence software is being developed and deployed to assist in the peer review process, Dr. Malički noted. In July 2020, Frontiers Science News debuted its Artificial Intelligence Review Assistant to help editors, reviewers, and authors evaluate the quality of a manuscript. The program can make up to 20 recommendations, including “the assessment of language quality, the detection of plagiarism, and identification of potential conflicts of interest.” The program is now in use in all 103 journals published by Frontiers. Preliminary software is also available to detect statistical errors.

Another system under development is FAIRware, an initiative of the Research on Research Institute in partnership with the Stanford Center for Biomedical Informatics Research. The partnership’s goal is to “develop an automated online tool (or suite of tools) to help researchers ensure that the datasets they produce are ‘FAIR’ at the point of creation,” said Dr. Malički, referring to the findability, accessibility, interoperability, and reusability (FAIR) guiding principles for data management. The principles aim to increase the ability of machines to automatically find and use the data, as well as to support its reuse by individuals.

He added that these advanced tools cannot replace human reviewers, who will “likely always be a necessary quality check in the process.”
 

Greater transparency needed

Another limitation of peer review is the reviewers themselves, according to Dr. Malički. “It’s a step in the right direction that The Lancet is now requesting a peer reviewer with expertise in big datasets, but it does not go far enough to increase accountability of peer reviewers,” he said.

Dr. Malički is the co–editor-in-chief of the journal Research Integrity and Peer Review , which has “an open and transparent review process – meaning that we reveal the names of the reviewers to the public and we publish the full review report alongside the paper.” The publication also allows the authors to make public the original version they sent.

Dr. Malički cited several advantages to transparent peer review, particularly the increased accountability that results from placing potential conflicts of interest under the microscope.

As for the concern that identifying the reviewers might soften the review process, “there is little evidence to substantiate that concern,” he added.

Dr. Malički emphasized that making reviews public “is not a problem – people voice strong opinions at conferences and elsewhere. The question remains, who gets to decide if the criticism has been adequately addressed, so that the findings of the study still stand?”

He acknowledged that, “as in politics and on many social platforms, rage, hatred, and personal attacks divert the discussion from the topic at hand, which is why a good moderator is needed.”

A journal editor or a moderator at a scientific conference may be tasked with “stopping all talk not directly related to the topic.”
 

Widening the circle of scrutiny

Dr. Malički added: “A published paper should not be considered the ‘final word,’ even if it has gone through peer review and is published in a reputable journal. The peer-review process means that a limited number of people have seen the study.”

Once the study is published, “the whole world gets to see it and criticize it, and that widens the circle of scrutiny.”

One classic way to raise concerns about a study post publication is to write a letter to the journal editor. But there is no guarantee that the letter will be published or the authors notified of the feedback.

Dr. Malički encourages readers to use PubPeer, an online forum in which members of the public can post comments on scientific studies and articles.

Once a comment is posted, the authors are alerted. “There is no ‘police department’ that forces authors to acknowledge comments or forces journal editors to take action, but at least PubPeer guarantees that readers’ messages will reach the authors and – depending on how many people raise similar issues – the comments can lead to errata or even full retractions,” he said.

PubPeer was key in pointing out errors in a suspect study from France (which did not involve Surgisphere) that supported the use of hydroxychloroquine in COVID-19.
 

A message to policy makers

High stakes are involved in ensuring the integrity of scientific publications: The French government revoked a decree that allowed hospitals to prescribe hydroxychloroquine for certain COVID-19 patients.

After the Surgisphere Lancet article, the World Health Organization temporarily halted enrollment in the hydroxychloroquine component of the Solidarity international randomized trial of medications to treat COVID-19.

Similarly, the U.K. Medicines and Healthcare Products Regulatory Agency instructed the organizers of COPCOV, an international trial of the use of hydroxychloroquine as prophylaxis against COVID-19, to suspend recruitment of patients. The SOLIDARITY trial briefly resumed, but that arm of the trial was ultimately suspended after a preliminary analysis suggested that hydroxychloroquine provided no benefit for patients with COVID-19.

Dr. Malički emphasized that governments and organizations should not “blindly trust journal articles” and make policy decisions based exclusively on study findings in published journals – even with the current improvements in the peer review process – without having their own experts conduct a thorough review of the data.

“If you are not willing to do your own due diligence, then at least be brave enough and say transparently why you are making this policy, or any other changes, and clearly state if your decision is based primarily or solely on the fact that ‘X’ study was published in ‘Y’ journal,” he stated.

Dr. Rao believes that the most important take-home message of the Surgisphere scandal is “that we should be skeptical and do our own due diligence about the kinds of data published – a responsibility that applies to all of us, whether we are investigators, editors at journals, the press, scientists, and readers.”

Dr. Rao reported being on the steering committee of the National Heart, Lung, and Blood Institute–sponsored MINT trial and the Bayer-sponsored PACIFIC AMI trial. Dr. Malički reports being a postdoc at METRICS Stanford in the past 3 years. Dr. Krumholz received expenses and/or personal fees from UnitedHealth, Element Science, Aetna, Facebook, the Siegfried and Jensen Law Firm, Arnold and Porter Law Firm, Martin/Baughman Law Firm, F-Prime, and the National Center for Cardiovascular Diseases in Beijing. He is an owner of Refactor Health and HugoHealth and had grants and/or contracts from the Centers for Medicare & Medicaid Services, the FDA, Johnson & Johnson, and the Shenzhen Center for Health Information.

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

In May 2020, two major scientific journals published and subsequently retracted studies that relied on data provided by the now-disgraced data analytics company Surgisphere.

One of the studies, published in The Lancet, reported an association between the antimalarial drugs hydroxychloroquine and chloroquine and increased in-hospital mortality and cardiac arrhythmias in patients with COVID-19. The second study, which appeared in the New England Journal of Medicine, described an association between underlying cardiovascular disease, but not related drug therapy, with increased mortality in COVID-19 patients.

The retractions in June 2020 followed an open letter to each publication penned by scientists, ethicists, and clinicians who flagged serious methodological and ethical anomalies in the data used in the studies.

On the 1-year anniversary, researchers and journal editors spoke about what was learned to reduce the risk of something like this happening again.

“The Surgisphere incident served as a wake-up call for everyone involved with scientific research to make sure that data have integrity and are robust,” Sunil Rao, MD, professor of medicine, Duke University Health System, Durham, N.C., and editor-in-chief of Circulation: Cardiovascular Interventions, said in an interview.

“I’m sure this isn’t going to be the last incident of this nature, and we have to be vigilant about new datasets or datasets that we haven’t heard of as having a track record of publication,” Dr. Rao said.
 

Spotlight on authors

The editors of the Lancet Group responded to the “wake-up call” with a statement, Learning From a Retraction, which announced changes to reduce the risks of research and publication misconduct.

The changes affect multiple phases of the publication process. For example, the declaration form that authors must sign “will require that more than one author has directly accessed and verified the data reported in the manuscript.” Additionally, when a research article is the result of an academic and commercial partnership – as was the case in the two retracted studies – “one of the authors named as having accessed and verified data must be from the academic team.”

This was particularly important because it appears that the academic coauthors of the retracted studies did not have access to the data provided by Surgisphere, a private commercial entity.

Mandeep R. Mehra, MD, William Harvey Distinguished Chair in Advanced Cardiovascular Medicine, Brigham and Women’s Hospital, Boston, who was the lead author of both studies, declined to be interviewed for this article. In a letter to the New England Journal of Medicine editors requesting that the article be retracted, he wrote: “Because all the authors were not granted access to the raw data and the raw data could not be made available to a third-party auditor, we are unable to validate the primary data sources underlying our article.”

In a similar communication with The Lancet, Dr. Mehra wrote even more pointedly that, in light of the refusal of Surgisphere to make the data available to the third-party auditor, “we can no longer vouch for the veracity of the primary data sources.”

“It is very disturbing that the authors were willing to put their names on a paper without ever seeing and verifying the data,” Mario Malički, MD, PhD, a postdoctoral researcher at METRICS at Stanford (Calif.) University, said in an interview. “Saying that they could ‘no longer vouch’ suggests that at one point they could vouch for it. Most likely they took its existence and veracity entirely on trust.”

Dr. Malički pointed out that one of the four criteria of the International Committee of Medical Journal Editors for being an author on a study is the “agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.”

The new policies put forth by The Lancet are “encouraging,” but perhaps do not go far enough. “Every author, not only one or two authors, should personally take responsibility for the integrity of data,” he stated.

Many journals “adhere to ICMJE rules in principle and have checkboxes for authors to confirm that they guarantee the veracity of the data.” However, they “do not have the resources to verify the authors’ statements.”

Ideally, “it is the institutions where the researchers work that should guarantee the veracity of the raw data – but I do not know any university or institute that does this,” he said.
 

No ‘good-housekeeping’ seal

For articles based on large, real-world datasets, the Lancet Group will now require that editors ensure that at least one peer reviewer is “knowledgeable about the details of the dataset being reported and can understand its strengths and limitations in relation to the question being addressed.”

For studies that use “very large datasets,” the editors are now required to ensure that, in addition to a statistical peer review, a review from an “expert in data science” is obtained. Reviewers will also be explicitly asked if they have “concerns about research integrity or publication ethics regarding the manuscript they are reviewing.”

Although these changes are encouraging, Harlan Krumholz, MD, professor of medicine (cardiology), Yale University, New Haven, Conn., is not convinced that they are realistic.

Dr. Krumholz, who is also the founder and director of the Yale New Haven Hospital Center for Outcome Research and Evaluation, said in an interview that “large, real-world datasets” are of two varieties. Datasets drawn from publicly available sources, such as Medicare or Medicaid health records, are utterly transparent.

By contrast, Surgisphere was a privately owned database, and “it is not unusual for privately owned databases to have proprietary data from multiple sources that the company may choose to keep confidential,” Dr. Krumholz said.

He noted that several large datasets are widely used for research purposes, such as IBM, Optum, and Komodo – a data analytics company that recently entered into partnership with a fourth company, PicnicHealth.

These companies receive deidentified electronic health records from health systems and insurers nationwide. Komodo boasts “real-time and longitudinal data on more than 325 million patients, representing more than 65 billion clinical encounters with 15 million new encounters added daily.”

“One has to raise an eyebrow – how were these data acquired? And, given that the U.S. has a population of around 328 million people, is it really plausible that a single company has health records of almost the entire U.S. population?” Dr. Krumholz commented. (A spokesperson for Komodo said in an interview that the company has records on 325 million U.S. patients.)

This is “an issue across the board with ‘real-world evidence,’ which is that it’s like the ‘Wild West’ – the transparencies of private databases are less than optimal and there are no common standards to help us move forward,” Dr. Krumholz said, noting that there is “no external authority overseeing, validating, or auditing these databases. In the end, we are trusting the companies.”

Although the Food and Drug Administration has laid out a framework for how real-world data and real-world evidence can be used to advance scientific research, the FDA does not oversee the databases.

“Thus, there is no ‘good housekeeping seal’ that a peer reviewer or author would be in a position to evaluate,” Dr. Krumholz said. “No journal can do an audit of these types of private databases, so ultimately, it boils down to trust.”

Nevertheless, there were red flags with Surgisphere, Dr. Rao pointed out. Unlike more established and widely used databases, the Surgisphere database had been catapulted from relative obscurity onto center stage, which should have given researchers pause.
 

AI-assisted peer review

A series of investigative reports by The Guardian raised questions about Sapan Desai, the CEO of Surgisphere, including the fact that hospitals purporting to have contributed data to Surgisphere had never heard of the company.

However, peer reviewers are not expected to be investigative reporters, explained Dr. Malički.

“In an ideal world, editors and peer reviewers would have a chance to look at raw data or would have a certificate from the academic institution the authors are affiliated with that the data have been inspected by the institution, but in the real world, of course, this does not happen,” he said.

Artificial intelligence software is being developed and deployed to assist in the peer review process, Dr. Malički noted. In July 2020, Frontiers Science News debuted its Artificial Intelligence Review Assistant to help editors, reviewers, and authors evaluate the quality of a manuscript. The program can make up to 20 recommendations, including “the assessment of language quality, the detection of plagiarism, and identification of potential conflicts of interest.” The program is now in use in all 103 journals published by Frontiers. Preliminary software is also available to detect statistical errors.

Another system under development is FAIRware, an initiative of the Research on Research Institute in partnership with the Stanford Center for Biomedical Informatics Research. The partnership’s goal is to “develop an automated online tool (or suite of tools) to help researchers ensure that the datasets they produce are ‘FAIR’ at the point of creation,” said Dr. Malički, referring to the findability, accessibility, interoperability, and reusability (FAIR) guiding principles for data management. The principles aim to increase the ability of machines to automatically find and use the data, as well as to support its reuse by individuals.

He added that these advanced tools cannot replace human reviewers, who will “likely always be a necessary quality check in the process.”
 

Greater transparency needed

Another limitation of peer review is the reviewers themselves, according to Dr. Malički. “It’s a step in the right direction that The Lancet is now requesting a peer reviewer with expertise in big datasets, but it does not go far enough to increase accountability of peer reviewers,” he said.

Dr. Malički is the co–editor-in-chief of the journal Research Integrity and Peer Review , which has “an open and transparent review process – meaning that we reveal the names of the reviewers to the public and we publish the full review report alongside the paper.” The publication also allows the authors to make public the original version they sent.

Dr. Malički cited several advantages to transparent peer review, particularly the increased accountability that results from placing potential conflicts of interest under the microscope.

As for the concern that identifying the reviewers might soften the review process, “there is little evidence to substantiate that concern,” he added.

Dr. Malički emphasized that making reviews public “is not a problem – people voice strong opinions at conferences and elsewhere. The question remains, who gets to decide if the criticism has been adequately addressed, so that the findings of the study still stand?”

He acknowledged that, “as in politics and on many social platforms, rage, hatred, and personal attacks divert the discussion from the topic at hand, which is why a good moderator is needed.”

A journal editor or a moderator at a scientific conference may be tasked with “stopping all talk not directly related to the topic.”
 

Widening the circle of scrutiny

Dr. Malički added: “A published paper should not be considered the ‘final word,’ even if it has gone through peer review and is published in a reputable journal. The peer-review process means that a limited number of people have seen the study.”

Once the study is published, “the whole world gets to see it and criticize it, and that widens the circle of scrutiny.”

One classic way to raise concerns about a study post publication is to write a letter to the journal editor. But there is no guarantee that the letter will be published or the authors notified of the feedback.

Dr. Malički encourages readers to use PubPeer, an online forum in which members of the public can post comments on scientific studies and articles.

Once a comment is posted, the authors are alerted. “There is no ‘police department’ that forces authors to acknowledge comments or forces journal editors to take action, but at least PubPeer guarantees that readers’ messages will reach the authors and – depending on how many people raise similar issues – the comments can lead to errata or even full retractions,” he said.

PubPeer was key in pointing out errors in a suspect study from France (which did not involve Surgisphere) that supported the use of hydroxychloroquine in COVID-19.
 

A message to policy makers

High stakes are involved in ensuring the integrity of scientific publications: The French government revoked a decree that allowed hospitals to prescribe hydroxychloroquine for certain COVID-19 patients.

After the Surgisphere Lancet article, the World Health Organization temporarily halted enrollment in the hydroxychloroquine component of the Solidarity international randomized trial of medications to treat COVID-19.

Similarly, the U.K. Medicines and Healthcare Products Regulatory Agency instructed the organizers of COPCOV, an international trial of the use of hydroxychloroquine as prophylaxis against COVID-19, to suspend recruitment of patients. The SOLIDARITY trial briefly resumed, but that arm of the trial was ultimately suspended after a preliminary analysis suggested that hydroxychloroquine provided no benefit for patients with COVID-19.

Dr. Malički emphasized that governments and organizations should not “blindly trust journal articles” and make policy decisions based exclusively on study findings in published journals – even with the current improvements in the peer review process – without having their own experts conduct a thorough review of the data.

“If you are not willing to do your own due diligence, then at least be brave enough and say transparently why you are making this policy, or any other changes, and clearly state if your decision is based primarily or solely on the fact that ‘X’ study was published in ‘Y’ journal,” he stated.

Dr. Rao believes that the most important take-home message of the Surgisphere scandal is “that we should be skeptical and do our own due diligence about the kinds of data published – a responsibility that applies to all of us, whether we are investigators, editors at journals, the press, scientists, and readers.”

Dr. Rao reported being on the steering committee of the National Heart, Lung, and Blood Institute–sponsored MINT trial and the Bayer-sponsored PACIFIC AMI trial. Dr. Malički reports being a postdoc at METRICS Stanford in the past 3 years. Dr. Krumholz received expenses and/or personal fees from UnitedHealth, Element Science, Aetna, Facebook, the Siegfried and Jensen Law Firm, Arnold and Porter Law Firm, Martin/Baughman Law Firm, F-Prime, and the National Center for Cardiovascular Diseases in Beijing. He is an owner of Refactor Health and HugoHealth and had grants and/or contracts from the Centers for Medicare & Medicaid Services, the FDA, Johnson & Johnson, and the Shenzhen Center for Health Information.

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

As doctors struggled through several surges of COVID-19 infections, most of what we learned was acquired through real-life experience. While many treatment options were promoted, most flat-out failed to be real therapeutics at all. Now that we have a safe and effective vaccine, we can prevent many infections from this virus. However, we are still left to manage the many post-COVID symptoms our patients continue to suffer with.

Symptoms following infection can last for months and range widely from “brain fog,” fatigue, dyspnea, chest pain, generalized weakness, depression, and a host of others. Patients may experience one or all of these symptoms, and there is currently no good way to predict who will go on to become a COVID “long hauler”.

Following the example of being educated by COVID as it happened, the same is true for managing post-COVID symptoms. The medical community still has a poor understanding of why some people develop it and there are few evidence-based studies to support any treatment modalities.

Earlier this month, the Centers for Disease Control and Prevention issued a set of clinical guidelines addressing treatment of post-COVID symptoms, which they define as “new, recurring, or ongoing symptoms more than 4 weeks after infection, sometimes after initial symptom recovery.” It is important to note that these symptoms can occur in any degree of sickness during the acute infection, including in those who were asymptomatic. Even the actual name of this post-COVID syndrome is still being developed, with several other names being used for it as well.

While the guidelines are quite extensive, the actual clinical recommendations are still vague. For example, it is advised to let the patient know that post-COVID symptoms are still not well understood. While it is important to be transparent with patients, this does little to reassure them. Patients look to doctors, especially their primary care physicians, to guide them on the best treatment paths. Yet, we currently have none for post-COVID syndrome.

It is also advised to treat the patients’ symptoms and help improve functioning. For many diseases, doctors like to get to the root cause of the problem. Treating a symptom often masks an underlying condition. It may make the patient feel better and improve what they are capable of doing, which is important, but it also fails to unmask the real problem. It is also important to note that symptoms can be out of proportion to clinical findings and should not be dismissed: we just don’t have the answers yet.

One helpful recommendation is having a patient keep a diary of their symptoms. This will help both the patient and doctor learn what may be triggering factors. If it is, for example, exertion that induces breathlessness, perhaps the patient can gradually increase their level of activity to minimize symptoms. Additionally, a “comprehensive rehabilitation program” is also advised and this can greatly assist addressing all the issues a patient is experiencing, physically and medically.

It is also advised that management of underlying medical conditions be optimized. While this is very important, it is not something specific to post-COVID syndrome: All patients should have their underlying medical conditions well controlled. It might be that the patient is paying more attention to their overall health, which is a good thing. However, this does not necessarily reduce the current symptoms a patient is experiencing.

The CDC makes a good attempt to offer guidance in the frustrating management of post-COVID syndrome. However, their clinical guidelines fail to offer specific management tools specific to treating post-COVID patients. The recommendations offered are more helpful to health in general. The fact that more specific recommendations are lacking is simply caused by the lack of knowledge of this condition at present. As more research is conducted and more knowledge obtained, new guidelines should become more detailed.

Dr. Girgis practices family medicine in South River, N.J., and is a clinical assistant professor of family medicine at Robert Wood Johnson Medical School, New Brunswick, N.J. You can contact her at [email protected].

As doctors struggled through several surges of COVID-19 infections, most of what we learned was acquired through real-life experience. While many treatment options were promoted, most flat-out failed to be real therapeutics at all. Now that we have a safe and effective vaccine, we can prevent many infections from this virus. However, we are still left to manage the many post-COVID symptoms our patients continue to suffer with.

Symptoms following infection can last for months and range widely from “brain fog,” fatigue, dyspnea, chest pain, generalized weakness, depression, and a host of others. Patients may experience one or all of these symptoms, and there is currently no good way to predict who will go on to become a COVID “long hauler”.

Following the example of being educated by COVID as it happened, the same is true for managing post-COVID symptoms. The medical community still has a poor understanding of why some people develop it and there are few evidence-based studies to support any treatment modalities.

Earlier this month, the Centers for Disease Control and Prevention issued a set of clinical guidelines addressing treatment of post-COVID symptoms, which they define as “new, recurring, or ongoing symptoms more than 4 weeks after infection, sometimes after initial symptom recovery.” It is important to note that these symptoms can occur in any degree of sickness during the acute infection, including in those who were asymptomatic. Even the actual name of this post-COVID syndrome is still being developed, with several other names being used for it as well.

While the guidelines are quite extensive, the actual clinical recommendations are still vague. For example, it is advised to let the patient know that post-COVID symptoms are still not well understood. While it is important to be transparent with patients, this does little to reassure them. Patients look to doctors, especially their primary care physicians, to guide them on the best treatment paths. Yet, we currently have none for post-COVID syndrome.

It is also advised to treat the patients’ symptoms and help improve functioning. For many diseases, doctors like to get to the root cause of the problem. Treating a symptom often masks an underlying condition. It may make the patient feel better and improve what they are capable of doing, which is important, but it also fails to unmask the real problem. It is also important to note that symptoms can be out of proportion to clinical findings and should not be dismissed: we just don’t have the answers yet.

One helpful recommendation is having a patient keep a diary of their symptoms. This will help both the patient and doctor learn what may be triggering factors. If it is, for example, exertion that induces breathlessness, perhaps the patient can gradually increase their level of activity to minimize symptoms. Additionally, a “comprehensive rehabilitation program” is also advised and this can greatly assist addressing all the issues a patient is experiencing, physically and medically.

It is also advised that management of underlying medical conditions be optimized. While this is very important, it is not something specific to post-COVID syndrome: All patients should have their underlying medical conditions well controlled. It might be that the patient is paying more attention to their overall health, which is a good thing. However, this does not necessarily reduce the current symptoms a patient is experiencing.

The CDC makes a good attempt to offer guidance in the frustrating management of post-COVID syndrome. However, their clinical guidelines fail to offer specific management tools specific to treating post-COVID patients. The recommendations offered are more helpful to health in general. The fact that more specific recommendations are lacking is simply caused by the lack of knowledge of this condition at present. As more research is conducted and more knowledge obtained, new guidelines should become more detailed.

Dr. Girgis practices family medicine in South River, N.J., and is a clinical assistant professor of family medicine at Robert Wood Johnson Medical School, New Brunswick, N.J. You can contact her at [email protected].

As doctors struggled through several surges of COVID-19 infections, most of what we learned was acquired through real-life experience. While many treatment options were promoted, most flat-out failed to be real therapeutics at all. Now that we have a safe and effective vaccine, we can prevent many infections from this virus. However, we are still left to manage the many post-COVID symptoms our patients continue to suffer with.

Symptoms following infection can last for months and range widely from “brain fog,” fatigue, dyspnea, chest pain, generalized weakness, depression, and a host of others. Patients may experience one or all of these symptoms, and there is currently no good way to predict who will go on to become a COVID “long hauler”.

Following the example of being educated by COVID as it happened, the same is true for managing post-COVID symptoms. The medical community still has a poor understanding of why some people develop it and there are few evidence-based studies to support any treatment modalities.

Earlier this month, the Centers for Disease Control and Prevention issued a set of clinical guidelines addressing treatment of post-COVID symptoms, which they define as “new, recurring, or ongoing symptoms more than 4 weeks after infection, sometimes after initial symptom recovery.” It is important to note that these symptoms can occur in any degree of sickness during the acute infection, including in those who were asymptomatic. Even the actual name of this post-COVID syndrome is still being developed, with several other names being used for it as well.

While the guidelines are quite extensive, the actual clinical recommendations are still vague. For example, it is advised to let the patient know that post-COVID symptoms are still not well understood. While it is important to be transparent with patients, this does little to reassure them. Patients look to doctors, especially their primary care physicians, to guide them on the best treatment paths. Yet, we currently have none for post-COVID syndrome.

It is also advised to treat the patients’ symptoms and help improve functioning. For many diseases, doctors like to get to the root cause of the problem. Treating a symptom often masks an underlying condition. It may make the patient feel better and improve what they are capable of doing, which is important, but it also fails to unmask the real problem. It is also important to note that symptoms can be out of proportion to clinical findings and should not be dismissed: we just don’t have the answers yet.

One helpful recommendation is having a patient keep a diary of their symptoms. This will help both the patient and doctor learn what may be triggering factors. If it is, for example, exertion that induces breathlessness, perhaps the patient can gradually increase their level of activity to minimize symptoms. Additionally, a “comprehensive rehabilitation program” is also advised and this can greatly assist addressing all the issues a patient is experiencing, physically and medically.

It is also advised that management of underlying medical conditions be optimized. While this is very important, it is not something specific to post-COVID syndrome: All patients should have their underlying medical conditions well controlled. It might be that the patient is paying more attention to their overall health, which is a good thing. However, this does not necessarily reduce the current symptoms a patient is experiencing.

The CDC makes a good attempt to offer guidance in the frustrating management of post-COVID syndrome. However, their clinical guidelines fail to offer specific management tools specific to treating post-COVID patients. The recommendations offered are more helpful to health in general. The fact that more specific recommendations are lacking is simply caused by the lack of knowledge of this condition at present. As more research is conducted and more knowledge obtained, new guidelines should become more detailed.

Dr. Girgis practices family medicine in South River, N.J., and is a clinical assistant professor of family medicine at Robert Wood Johnson Medical School, New Brunswick, N.J. You can contact her at [email protected].

Psoriasis patients treated with biological disease-modifying antirheumatic drugs had a significantly lower incidence of psoriatic arthritis (PsA) compared with those treated with phototherapy, in a study of 464 adults.

Epidemiologic data show that PsA may be diagnosed as long as 5-10 years after a diagnosis of plaque psoriasis, but PsA ultimately occurs in up to 25% of cases, wrote the study investigators, Paolo Gisondi, MD, of the section of dermatology and venereology, department of medicine, at Università degli Studi di Verona, Italy, and colleagues.

“The delay between the onset of skin manifestations of psoriasis and joint disease may provide a therapeutic window of clinical opportunity for preventing the progression from psoriasis to PsA,” but the impact of continuous systemic treatment with biological disease-modifying antirheumatic drugs (DMARDs) has not been well studied, the researchers said.

In the retrospective, nonrandomized study published in Annals of the Rheumatic Diseases, the researchers reviewed data from adults with moderate to severe plaque psoriasis who received continuous treatment with biologic DMARDs, compared with those who received narrow-band ultraviolet light B (nb-UVB) phototherapy, between January 2012 and September 2020.

Patients with a past or present PsA diagnosis were excluded from the study. A total of 234 patients were treated with biologic DMARDs for at least 5 years and 230 were treated with at least three courses of nb-UVB phototherapy; all patients were followed for an average of 7 years.

PsA was determined based on the Classification for Psoriatic Arthritis criteria. Incidence was defined in terms of cases per 100 patients per year.

During the follow-up period, 51 patients (11%) developed incident PsA: 19 (8%) in the biologic DMARDs group and 32 (14%) in the nb-UVB phototherapy group. The annual incidence rate of PsA was 1.20 cases per 100 patients per year in the biologic DMARDs group compared with 2.17 cases per 100 patients per year in the phototherapy group (P = .006).

In a multivariate analysis, independent risk factors for PsA were older age (adjusted hazard ratio, 1.04; P < .001), nail psoriasis (aHR 3.15; P = .001), and psoriasis duration greater than 10 years (aHR, 2.02; P = .001). Most other baseline demographics, including smoking status, baseline Psoriasis Area and Severity Index (PASI) scores, and comorbidities, were similar in patients who did and did not develop PsA.

Of the patients taking biologic DMARDs, 39 (17%) were treated with infliximab, 17 (7%) with etanercept, 67 (29%) with adalimumab, 50 (21%) with ustekinumab, and 61 (26%) with secukinumab; 35 of these patients switched biologics during the study period.

The study findings were limited by several factors including the retrospective design and the resulting potential for biases, notably the potential confounding bias by indication because of the lack of randomization, the researchers noted. Another limitation was the inability to perform a subgroup analysis of biologic DMARD classes because of the small sample size, the authors said. However, they added, the findings were strengthened by the complete database and accurate PsA diagnoses supported by an expert rheumatologist.

Larger prospective and intervention studies are needed to validate the results, the researchers emphasized. However, data from the current study suggest that continued treatment with biologic DMARDs “may reduce the risk of incident PsA in patients with moderate to severe chronic plaque psoriasis,” they concluded.

The study was supported by the European Union’s Horizon 2020 Research and Innovation Program. Dr. Gisondi and several coauthors disclosed relationships with Abbvie, Almirall, Amgen, Janssen, Leo Pharma, Eli Lilly, Novartis, Pierre Fabre, Sandoz, Sanofi, and UCB. The study was supported by the European Union’s Horizon 2020 Research and Innovation Program.

Psoriasis patients treated with biological disease-modifying antirheumatic drugs had a significantly lower incidence of psoriatic arthritis (PsA) compared with those treated with phototherapy, in a study of 464 adults.

Epidemiologic data show that PsA may be diagnosed as long as 5-10 years after a diagnosis of plaque psoriasis, but PsA ultimately occurs in up to 25% of cases, wrote the study investigators, Paolo Gisondi, MD, of the section of dermatology and venereology, department of medicine, at Università degli Studi di Verona, Italy, and colleagues.

“The delay between the onset of skin manifestations of psoriasis and joint disease may provide a therapeutic window of clinical opportunity for preventing the progression from psoriasis to PsA,” but the impact of continuous systemic treatment with biological disease-modifying antirheumatic drugs (DMARDs) has not been well studied, the researchers said.

In the retrospective, nonrandomized study published in Annals of the Rheumatic Diseases, the researchers reviewed data from adults with moderate to severe plaque psoriasis who received continuous treatment with biologic DMARDs, compared with those who received narrow-band ultraviolet light B (nb-UVB) phototherapy, between January 2012 and September 2020.

Patients with a past or present PsA diagnosis were excluded from the study. A total of 234 patients were treated with biologic DMARDs for at least 5 years and 230 were treated with at least three courses of nb-UVB phototherapy; all patients were followed for an average of 7 years.

PsA was determined based on the Classification for Psoriatic Arthritis criteria. Incidence was defined in terms of cases per 100 patients per year.

During the follow-up period, 51 patients (11%) developed incident PsA: 19 (8%) in the biologic DMARDs group and 32 (14%) in the nb-UVB phototherapy group. The annual incidence rate of PsA was 1.20 cases per 100 patients per year in the biologic DMARDs group compared with 2.17 cases per 100 patients per year in the phototherapy group (P = .006).

In a multivariate analysis, independent risk factors for PsA were older age (adjusted hazard ratio, 1.04; P < .001), nail psoriasis (aHR 3.15; P = .001), and psoriasis duration greater than 10 years (aHR, 2.02; P = .001). Most other baseline demographics, including smoking status, baseline Psoriasis Area and Severity Index (PASI) scores, and comorbidities, were similar in patients who did and did not develop PsA.

Of the patients taking biologic DMARDs, 39 (17%) were treated with infliximab, 17 (7%) with etanercept, 67 (29%) with adalimumab, 50 (21%) with ustekinumab, and 61 (26%) with secukinumab; 35 of these patients switched biologics during the study period.

The study findings were limited by several factors including the retrospective design and the resulting potential for biases, notably the potential confounding bias by indication because of the lack of randomization, the researchers noted. Another limitation was the inability to perform a subgroup analysis of biologic DMARD classes because of the small sample size, the authors said. However, they added, the findings were strengthened by the complete database and accurate PsA diagnoses supported by an expert rheumatologist.

Larger prospective and intervention studies are needed to validate the results, the researchers emphasized. However, data from the current study suggest that continued treatment with biologic DMARDs “may reduce the risk of incident PsA in patients with moderate to severe chronic plaque psoriasis,” they concluded.

The study was supported by the European Union’s Horizon 2020 Research and Innovation Program. Dr. Gisondi and several coauthors disclosed relationships with Abbvie, Almirall, Amgen, Janssen, Leo Pharma, Eli Lilly, Novartis, Pierre Fabre, Sandoz, Sanofi, and UCB. The study was supported by the European Union’s Horizon 2020 Research and Innovation Program.

Psoriasis patients treated with biological disease-modifying antirheumatic drugs had a significantly lower incidence of psoriatic arthritis (PsA) compared with those treated with phototherapy, in a study of 464 adults.

Epidemiologic data show that PsA may be diagnosed as long as 5-10 years after a diagnosis of plaque psoriasis, but PsA ultimately occurs in up to 25% of cases, wrote the study investigators, Paolo Gisondi, MD, of the section of dermatology and venereology, department of medicine, at Università degli Studi di Verona, Italy, and colleagues.

“The delay between the onset of skin manifestations of psoriasis and joint disease may provide a therapeutic window of clinical opportunity for preventing the progression from psoriasis to PsA,” but the impact of continuous systemic treatment with biological disease-modifying antirheumatic drugs (DMARDs) has not been well studied, the researchers said.

In the retrospective, nonrandomized study published in Annals of the Rheumatic Diseases, the researchers reviewed data from adults with moderate to severe plaque psoriasis who received continuous treatment with biologic DMARDs, compared with those who received narrow-band ultraviolet light B (nb-UVB) phototherapy, between January 2012 and September 2020.

Patients with a past or present PsA diagnosis were excluded from the study. A total of 234 patients were treated with biologic DMARDs for at least 5 years and 230 were treated with at least three courses of nb-UVB phototherapy; all patients were followed for an average of 7 years.

PsA was determined based on the Classification for Psoriatic Arthritis criteria. Incidence was defined in terms of cases per 100 patients per year.

During the follow-up period, 51 patients (11%) developed incident PsA: 19 (8%) in the biologic DMARDs group and 32 (14%) in the nb-UVB phototherapy group. The annual incidence rate of PsA was 1.20 cases per 100 patients per year in the biologic DMARDs group compared with 2.17 cases per 100 patients per year in the phototherapy group (P = .006).

In a multivariate analysis, independent risk factors for PsA were older age (adjusted hazard ratio, 1.04; P < .001), nail psoriasis (aHR 3.15; P = .001), and psoriasis duration greater than 10 years (aHR, 2.02; P = .001). Most other baseline demographics, including smoking status, baseline Psoriasis Area and Severity Index (PASI) scores, and comorbidities, were similar in patients who did and did not develop PsA.

Of the patients taking biologic DMARDs, 39 (17%) were treated with infliximab, 17 (7%) with etanercept, 67 (29%) with adalimumab, 50 (21%) with ustekinumab, and 61 (26%) with secukinumab; 35 of these patients switched biologics during the study period.

The study findings were limited by several factors including the retrospective design and the resulting potential for biases, notably the potential confounding bias by indication because of the lack of randomization, the researchers noted. Another limitation was the inability to perform a subgroup analysis of biologic DMARD classes because of the small sample size, the authors said. However, they added, the findings were strengthened by the complete database and accurate PsA diagnoses supported by an expert rheumatologist.

Larger prospective and intervention studies are needed to validate the results, the researchers emphasized. However, data from the current study suggest that continued treatment with biologic DMARDs “may reduce the risk of incident PsA in patients with moderate to severe chronic plaque psoriasis,” they concluded.

The study was supported by the European Union’s Horizon 2020 Research and Innovation Program. Dr. Gisondi and several coauthors disclosed relationships with Abbvie, Almirall, Amgen, Janssen, Leo Pharma, Eli Lilly, Novartis, Pierre Fabre, Sandoz, Sanofi, and UCB. The study was supported by the European Union’s Horizon 2020 Research and Innovation Program.