MDedge Neurology

This is getting pretty ridiculous. The number of well-done, evidence-based trials of hydroxychloroquine in COVID-19 showing minimal-to-no benefit is increasing. There are still studies that show benefit in certain cases, but many of them are small-scale or even anecdotal.

How long is this going to go on? If the evidence supporting its use were to be put through the standard Food and Drug Administration approval panels it wouldn’t have a chance.

Yet, because it’s become a political football (like masks), science and rational research are tossed out the window. At the end of July we were all treated to videos of Dr. Stella Immanuel claiming the drug is a cure. Dr. Immanuel may have medical credentials, but she also supports beliefs that space aliens and the Illuminati are involved in running governments, and that multiple gynecologic disorders are caused by sexual relations with demons and witches during dreams.

Even so, her hydroxychloroquine statements were given heavy play during a news cycle, then endorsed by the president and his supporters, all with very little immediate background provided for other claims she’s made in the past.

Medicine is a science. Politics shouldn’t be. While hydroxychloroquine may have its uses for other disorders, at this point COVID-19 doesn’t appear to be one of them. Continuing to give it to sick people, despite the growing evidence against it, violates the “do-no-harm” tenet of our field.

There was no shame in trying it and failing. This is the process through which all treatments are tested. If they work (such as with penicillin, for example) that’s wonderful. If they fail (such as with countless Alzheimer’s trials) we learn what doesn’t work and move on.

But to keep claiming success where there isn’t any moves beyond science and into things that whiff of a hoax, such as 1989’s cold fusion or recurrent claims of capturing Bigfoot.

With an implacable enemy such as COVID-19 at the door, money and effort need to be focused on finding what works, not on putting stale milk back in the refrigerator and hoping it comes out fresh.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

This is getting pretty ridiculous. The number of well-done, evidence-based trials of hydroxychloroquine in COVID-19 showing minimal-to-no benefit is increasing. There are still studies that show benefit in certain cases, but many of them are small-scale or even anecdotal.

How long is this going to go on? If the evidence supporting its use were to be put through the standard Food and Drug Administration approval panels it wouldn’t have a chance.

Yet, because it’s become a political football (like masks), science and rational research are tossed out the window. At the end of July we were all treated to videos of Dr. Stella Immanuel claiming the drug is a cure. Dr. Immanuel may have medical credentials, but she also supports beliefs that space aliens and the Illuminati are involved in running governments, and that multiple gynecologic disorders are caused by sexual relations with demons and witches during dreams.

Even so, her hydroxychloroquine statements were given heavy play during a news cycle, then endorsed by the president and his supporters, all with very little immediate background provided for other claims she’s made in the past.

Medicine is a science. Politics shouldn’t be. While hydroxychloroquine may have its uses for other disorders, at this point COVID-19 doesn’t appear to be one of them. Continuing to give it to sick people, despite the growing evidence against it, violates the “do-no-harm” tenet of our field.

There was no shame in trying it and failing. This is the process through which all treatments are tested. If they work (such as with penicillin, for example) that’s wonderful. If they fail (such as with countless Alzheimer’s trials) we learn what doesn’t work and move on.

But to keep claiming success where there isn’t any moves beyond science and into things that whiff of a hoax, such as 1989’s cold fusion or recurrent claims of capturing Bigfoot.

With an implacable enemy such as COVID-19 at the door, money and effort need to be focused on finding what works, not on putting stale milk back in the refrigerator and hoping it comes out fresh.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

This is getting pretty ridiculous. The number of well-done, evidence-based trials of hydroxychloroquine in COVID-19 showing minimal-to-no benefit is increasing. There are still studies that show benefit in certain cases, but many of them are small-scale or even anecdotal.

How long is this going to go on? If the evidence supporting its use were to be put through the standard Food and Drug Administration approval panels it wouldn’t have a chance.

Yet, because it’s become a political football (like masks), science and rational research are tossed out the window. At the end of July we were all treated to videos of Dr. Stella Immanuel claiming the drug is a cure. Dr. Immanuel may have medical credentials, but she also supports beliefs that space aliens and the Illuminati are involved in running governments, and that multiple gynecologic disorders are caused by sexual relations with demons and witches during dreams.

Even so, her hydroxychloroquine statements were given heavy play during a news cycle, then endorsed by the president and his supporters, all with very little immediate background provided for other claims she’s made in the past.

Medicine is a science. Politics shouldn’t be. While hydroxychloroquine may have its uses for other disorders, at this point COVID-19 doesn’t appear to be one of them. Continuing to give it to sick people, despite the growing evidence against it, violates the “do-no-harm” tenet of our field.

There was no shame in trying it and failing. This is the process through which all treatments are tested. If they work (such as with penicillin, for example) that’s wonderful. If they fail (such as with countless Alzheimer’s trials) we learn what doesn’t work and move on.

But to keep claiming success where there isn’t any moves beyond science and into things that whiff of a hoax, such as 1989’s cold fusion or recurrent claims of capturing Bigfoot.

With an implacable enemy such as COVID-19 at the door, money and effort need to be focused on finding what works, not on putting stale milk back in the refrigerator and hoping it comes out fresh.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

A blood test that measures plasma tau phosphorylated at threonine 217 (P-tau217) can accurately distinguish Alzheimer’s disease from other neurodegenerative disorders, new research suggests.

Results from a large multinational study showed that the level of P-tau217 in blood collected during life was an accurate predictor of tau brain changes seen in brain tissue after death. In addition, increasing blood P-tau217 levels can be detected in some individuals up to 20 years before the average age of onset of the early cognitive decline that signals Alzheimer’s disease, researchers reported.

“While there is still more work to be done, this biomarker has the potential to have a transformational impact on research, treatment, prevention, and therapy development, and in the clinical setting,” said senior author Eric M. Reiman, MD, executive director of Banner Alzheimer’s Institute in Phoenix.

The findings were presented at the virtual annual meeting of the Alzheimer’s Association International Conference and simultaneously published online July 28 in JAMA.

Three cohorts

The international team of researchers evaluated the P-tau217 blood test in 1,402 adults from three cohorts. The first cohort was made up of 81 individuals in the Arizona (Banner Sun Health Research Institute) Brain Donation program and included clinical, blood, and neuropathologic data. The second cohort included 699 individuals in the Swedish BioFINDER-2 study and provided clinical, brain imaging, cerebrospinal fluid (CSF), and blood data. The third cohort was made up of 522 participants from the Columbian autosomal-dominant Alzheimer’s disease kindred, including 365 PSEN1 E280A mutation carriers and 257 mutation noncarriers.

In the Arizona cohort, plasma P-tau217 discriminated neuropathologically defined Alzheimer’s disease from non-Alzheimer’s disease (area under the curve, 0.89; 95% CI, 0.81-0.97) with significantly higher accuracy than plasma P-tau181 and neurofilament light chain (NfL) (AUC range, 0.50-0.72; P < .05).

In the Swedish BioFINDER-2 cohort, the discriminative accuracy of plasma P-tau217 for clinical Alzheimer’s disease dementia versus other neurodegenerative diseases was 96% (AUC, 0.96; 95% CI, 0.93-0.98).

This was significantly higher than plasma P-tau181, plasma NfL, and MRI measures (AUC range, 0.50-0.81; P < .001), but was not significantly different than CSF P-tau217, CSF P-tau181, and tau-PET (AUC range, 0.90-0.99; P > .15).

In the Colombian cohort, plasma P-tau217 levels were significantly greater among PSEN1 mutation carriers than noncarriers starting at around age 25 years, which is 20 years prior to the estimated onset of mild cognitive impairment among mutation carriers.

Additionally, plasma P-tau217 levels correlated with cerebral tau tangles, and discriminated abnormal versus normal tau-PET scans with significantly higher accuracy than plasma P-tau181, plasma NfL, CSF P-tau181, CSF Abeta42:Abeta40 ratio, and MRI measures.

The blood test “opens the possibility of early diagnosis of Alzheimer’s disease before the dementia stage, which is very important for clinical trials evaluating novel therapies that might stop or slow down the disease process,” presenting author Oskar Hansson, MD, PhD, of Lund (Sweden) University, said in a statement.

Further research is now needed to optimize the P-tau217 blood test, validate the findings in unselected and diverse populations, and determine its potential role in the clinic, the investigators noted.

Potential game changer?

Commenting on the study, Howard Fillit, MD, founding executive director and chief science officer of the Alzheimer’s Drug Discovery Foundation, noted his enthusiasm for the test. “This tau blood test will be a real game changer, advancing clinical care and research,” said Dr. Fillit, who was not involved in the research.

“This is a real breakthrough: a simple and accessible blood test that can diagnose Alzheimer’s disease better than the more costly and invasive methods currently available like PET scans and cerebrospinal fluid biomarkers,” he said.

The P-tau217 blood test “is like the equivalent of the cholesterol test for heart disease, but for Alzheimer’s disease,” Dr. Fillit added.

As previously reported, another study presented at AAIC 2020 compared P-tau217 with P-tau181 to determine which could best identify individuals with Alzheimer’s disease. Results showed that, although the two biomarkers were similar overall, P-tau217 had a slight edge in terms of accuracy.

The study by Reiman et al. was funded by the Swedish Research Council, the Knut and Alice Wallenberg Foundation, and the Swedish Alzheimer Foundation. Dr. Hansson reported receiving grants from Roche, Biogen, and Pfizer, and receiving nonfinancial support from GE Healthcare, AVID Radiopharmaceuticals, and Euroimmun. Dr. Reiman has received grants from Roche/Roche Diagnostics and received personal fees from Alkahest, Alzheon, Aural Analytics, Denali, Green Valley, MagQ, Takeda/Zinfandel, and United Neuroscience. He is also a cofounder of AlzPath, which aims to further develop P-tau217 and fluid biomarkers; holds a patent owned by Banner Health for a strategy to use biomarkers to accelerate evaluation of Alzheimer prevention therapies; and is a principal investigator of prevention trials that include research agreements with Genentech/Roche and Novartis/Amgen, PET studies that include research agreements with Avid/Lilly, and several National Institute of Health–supported research studies. Dr. Fillit reported no relevant financial relationships.

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

A blood test that measures plasma tau phosphorylated at threonine 217 (P-tau217) can accurately distinguish Alzheimer’s disease from other neurodegenerative disorders, new research suggests.

Results from a large multinational study showed that the level of P-tau217 in blood collected during life was an accurate predictor of tau brain changes seen in brain tissue after death. In addition, increasing blood P-tau217 levels can be detected in some individuals up to 20 years before the average age of onset of the early cognitive decline that signals Alzheimer’s disease, researchers reported.

“While there is still more work to be done, this biomarker has the potential to have a transformational impact on research, treatment, prevention, and therapy development, and in the clinical setting,” said senior author Eric M. Reiman, MD, executive director of Banner Alzheimer’s Institute in Phoenix.

The findings were presented at the virtual annual meeting of the Alzheimer’s Association International Conference and simultaneously published online July 28 in JAMA.

Three cohorts

The international team of researchers evaluated the P-tau217 blood test in 1,402 adults from three cohorts. The first cohort was made up of 81 individuals in the Arizona (Banner Sun Health Research Institute) Brain Donation program and included clinical, blood, and neuropathologic data. The second cohort included 699 individuals in the Swedish BioFINDER-2 study and provided clinical, brain imaging, cerebrospinal fluid (CSF), and blood data. The third cohort was made up of 522 participants from the Columbian autosomal-dominant Alzheimer’s disease kindred, including 365 PSEN1 E280A mutation carriers and 257 mutation noncarriers.

In the Arizona cohort, plasma P-tau217 discriminated neuropathologically defined Alzheimer’s disease from non-Alzheimer’s disease (area under the curve, 0.89; 95% CI, 0.81-0.97) with significantly higher accuracy than plasma P-tau181 and neurofilament light chain (NfL) (AUC range, 0.50-0.72; P < .05).

In the Swedish BioFINDER-2 cohort, the discriminative accuracy of plasma P-tau217 for clinical Alzheimer’s disease dementia versus other neurodegenerative diseases was 96% (AUC, 0.96; 95% CI, 0.93-0.98).

This was significantly higher than plasma P-tau181, plasma NfL, and MRI measures (AUC range, 0.50-0.81; P < .001), but was not significantly different than CSF P-tau217, CSF P-tau181, and tau-PET (AUC range, 0.90-0.99; P > .15).

In the Colombian cohort, plasma P-tau217 levels were significantly greater among PSEN1 mutation carriers than noncarriers starting at around age 25 years, which is 20 years prior to the estimated onset of mild cognitive impairment among mutation carriers.

Additionally, plasma P-tau217 levels correlated with cerebral tau tangles, and discriminated abnormal versus normal tau-PET scans with significantly higher accuracy than plasma P-tau181, plasma NfL, CSF P-tau181, CSF Abeta42:Abeta40 ratio, and MRI measures.

The blood test “opens the possibility of early diagnosis of Alzheimer’s disease before the dementia stage, which is very important for clinical trials evaluating novel therapies that might stop or slow down the disease process,” presenting author Oskar Hansson, MD, PhD, of Lund (Sweden) University, said in a statement.

Further research is now needed to optimize the P-tau217 blood test, validate the findings in unselected and diverse populations, and determine its potential role in the clinic, the investigators noted.

Potential game changer?

Commenting on the study, Howard Fillit, MD, founding executive director and chief science officer of the Alzheimer’s Drug Discovery Foundation, noted his enthusiasm for the test. “This tau blood test will be a real game changer, advancing clinical care and research,” said Dr. Fillit, who was not involved in the research.

“This is a real breakthrough: a simple and accessible blood test that can diagnose Alzheimer’s disease better than the more costly and invasive methods currently available like PET scans and cerebrospinal fluid biomarkers,” he said.

The P-tau217 blood test “is like the equivalent of the cholesterol test for heart disease, but for Alzheimer’s disease,” Dr. Fillit added.

As previously reported, another study presented at AAIC 2020 compared P-tau217 with P-tau181 to determine which could best identify individuals with Alzheimer’s disease. Results showed that, although the two biomarkers were similar overall, P-tau217 had a slight edge in terms of accuracy.

The study by Reiman et al. was funded by the Swedish Research Council, the Knut and Alice Wallenberg Foundation, and the Swedish Alzheimer Foundation. Dr. Hansson reported receiving grants from Roche, Biogen, and Pfizer, and receiving nonfinancial support from GE Healthcare, AVID Radiopharmaceuticals, and Euroimmun. Dr. Reiman has received grants from Roche/Roche Diagnostics and received personal fees from Alkahest, Alzheon, Aural Analytics, Denali, Green Valley, MagQ, Takeda/Zinfandel, and United Neuroscience. He is also a cofounder of AlzPath, which aims to further develop P-tau217 and fluid biomarkers; holds a patent owned by Banner Health for a strategy to use biomarkers to accelerate evaluation of Alzheimer prevention therapies; and is a principal investigator of prevention trials that include research agreements with Genentech/Roche and Novartis/Amgen, PET studies that include research agreements with Avid/Lilly, and several National Institute of Health–supported research studies. Dr. Fillit reported no relevant financial relationships.

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

A blood test that measures plasma tau phosphorylated at threonine 217 (P-tau217) can accurately distinguish Alzheimer’s disease from other neurodegenerative disorders, new research suggests.

Results from a large multinational study showed that the level of P-tau217 in blood collected during life was an accurate predictor of tau brain changes seen in brain tissue after death. In addition, increasing blood P-tau217 levels can be detected in some individuals up to 20 years before the average age of onset of the early cognitive decline that signals Alzheimer’s disease, researchers reported.

“While there is still more work to be done, this biomarker has the potential to have a transformational impact on research, treatment, prevention, and therapy development, and in the clinical setting,” said senior author Eric M. Reiman, MD, executive director of Banner Alzheimer’s Institute in Phoenix.

The findings were presented at the virtual annual meeting of the Alzheimer’s Association International Conference and simultaneously published online July 28 in JAMA.

Three cohorts

The international team of researchers evaluated the P-tau217 blood test in 1,402 adults from three cohorts. The first cohort was made up of 81 individuals in the Arizona (Banner Sun Health Research Institute) Brain Donation program and included clinical, blood, and neuropathologic data. The second cohort included 699 individuals in the Swedish BioFINDER-2 study and provided clinical, brain imaging, cerebrospinal fluid (CSF), and blood data. The third cohort was made up of 522 participants from the Columbian autosomal-dominant Alzheimer’s disease kindred, including 365 PSEN1 E280A mutation carriers and 257 mutation noncarriers.

In the Arizona cohort, plasma P-tau217 discriminated neuropathologically defined Alzheimer’s disease from non-Alzheimer’s disease (area under the curve, 0.89; 95% CI, 0.81-0.97) with significantly higher accuracy than plasma P-tau181 and neurofilament light chain (NfL) (AUC range, 0.50-0.72; P < .05).

In the Swedish BioFINDER-2 cohort, the discriminative accuracy of plasma P-tau217 for clinical Alzheimer’s disease dementia versus other neurodegenerative diseases was 96% (AUC, 0.96; 95% CI, 0.93-0.98).

This was significantly higher than plasma P-tau181, plasma NfL, and MRI measures (AUC range, 0.50-0.81; P < .001), but was not significantly different than CSF P-tau217, CSF P-tau181, and tau-PET (AUC range, 0.90-0.99; P > .15).

In the Colombian cohort, plasma P-tau217 levels were significantly greater among PSEN1 mutation carriers than noncarriers starting at around age 25 years, which is 20 years prior to the estimated onset of mild cognitive impairment among mutation carriers.

Additionally, plasma P-tau217 levels correlated with cerebral tau tangles, and discriminated abnormal versus normal tau-PET scans with significantly higher accuracy than plasma P-tau181, plasma NfL, CSF P-tau181, CSF Abeta42:Abeta40 ratio, and MRI measures.

The blood test “opens the possibility of early diagnosis of Alzheimer’s disease before the dementia stage, which is very important for clinical trials evaluating novel therapies that might stop or slow down the disease process,” presenting author Oskar Hansson, MD, PhD, of Lund (Sweden) University, said in a statement.

Further research is now needed to optimize the P-tau217 blood test, validate the findings in unselected and diverse populations, and determine its potential role in the clinic, the investigators noted.

Potential game changer?

Commenting on the study, Howard Fillit, MD, founding executive director and chief science officer of the Alzheimer’s Drug Discovery Foundation, noted his enthusiasm for the test. “This tau blood test will be a real game changer, advancing clinical care and research,” said Dr. Fillit, who was not involved in the research.

“This is a real breakthrough: a simple and accessible blood test that can diagnose Alzheimer’s disease better than the more costly and invasive methods currently available like PET scans and cerebrospinal fluid biomarkers,” he said.

The P-tau217 blood test “is like the equivalent of the cholesterol test for heart disease, but for Alzheimer’s disease,” Dr. Fillit added.

As previously reported, another study presented at AAIC 2020 compared P-tau217 with P-tau181 to determine which could best identify individuals with Alzheimer’s disease. Results showed that, although the two biomarkers were similar overall, P-tau217 had a slight edge in terms of accuracy.

The study by Reiman et al. was funded by the Swedish Research Council, the Knut and Alice Wallenberg Foundation, and the Swedish Alzheimer Foundation. Dr. Hansson reported receiving grants from Roche, Biogen, and Pfizer, and receiving nonfinancial support from GE Healthcare, AVID Radiopharmaceuticals, and Euroimmun. Dr. Reiman has received grants from Roche/Roche Diagnostics and received personal fees from Alkahest, Alzheon, Aural Analytics, Denali, Green Valley, MagQ, Takeda/Zinfandel, and United Neuroscience. He is also a cofounder of AlzPath, which aims to further develop P-tau217 and fluid biomarkers; holds a patent owned by Banner Health for a strategy to use biomarkers to accelerate evaluation of Alzheimer prevention therapies; and is a principal investigator of prevention trials that include research agreements with Genentech/Roche and Novartis/Amgen, PET studies that include research agreements with Avid/Lilly, and several National Institute of Health–supported research studies. Dr. Fillit reported no relevant financial relationships.

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

The novel, orally administered calcitonin gene-related peptide (CGRP) antagonist atogepant has met the primary endpoint in a phase 3 trial for migraine prevention, AbbVie, the company developing the drug, has announced.

Top-line results from the ADVANCE trial, which evaluated atogepant 10, 30, and 60 mg, showed all three doses were associated with a significant reduction from baseline in mean monthly migraine days, compared with placebo.

There were also significant improvements in all six secondary endpoints with the two higher doses.

Data from the ADVANCE trial and a previous phase 2/3 trial will be the basis for regulatory submissions in the United States and other countries, AbbVie reported.

Decreased migraine days

The phase 3, multicenter, randomized, double-blind, placebo-controlled, parallel-group trial was designed to evaluate the efficacy, safety, and tolerability of oral atogepant for the prevention of migraine in those who experienced 4-14 migraine days per month.

A total of 910 patients were randomized to one of four treatment groups: 10 mg, 30 mg, or 60 mg of atogepant once daily or placebo. Efficacy analyses were based on the modified intent-to-treat population of 873 patients.

The primary endpoint was change from baseline in mean monthly migraine days during the 12-week treatment period. All atogepant dose groups met the primary endpoint and demonstrated significantly greater decreases in mean monthly migraine days, compared with placebo.

Mean monthly migraine days were reduced by 3.69 days with the 10-mg dose, 3.86 days with the 30-mg dose, and 4.2 days with the 60-mg dose of atogepant, compared with a reduction of 2.48 migraine days in the placebo group (P < .0001, all dose groups vs. placebo).

A key secondary endpoint measured the proportion of patients who achieved at least a 50% reduction in mean monthly migraine days over 12 weeks. This outcome occurred in 55.6% of the 10-mg atogepant group, 58.7% of the 30-mg group, and 60.8% of the 60-mg group, compared with 29% of the placebo group (P < .0001, all dose groups vs. placebo).

Significant improvements

Additional secondary endpoints measured during the 12-week treatment period included change from baseline in mean monthly headache days, mean monthly acute–medication use days, mean monthly performance of daily activities and physical impairment domain scores on the Activity Impairment in Migraine-Diary, and change from baseline in the Migraine-Specific Quality of Life Questionnaire Role Function-Restrictive domain score at week 12. Treatment with the 30-mg and 60-mg doses resulted in significant improvements in all secondary endpoints, and treatment with the 10-mg dose resulted in significant improvements in four of the six secondary endpoints.

No new safety risks were observed when compared with the safety profile of atogepant observed in previous trials, AbbVie said. Serious adverse events occurred in 0.9% of patients in the atogepant 10-mg group versus 0.9% of patients in the placebo group. No patients in the atogepant 30-mg or 60-mg groups experienced a serious adverse event. The most common adverse events (reported in at least 5% of patients and at least one atogepant group and at a rate greater than placebo), across all doses versus placebo, were constipation (6.9%-7.7% vs. 0.5%), nausea (4.4%-6.1% vs. 1.8%), and upper respiratory tract infection (3.9%-5.7% vs. 4.5%).

Most cases of constipation, nausea, and upper respiratory tract infection were mild or moderate in severity and did not lead to discontinuation. There were no hepatic safety issues identified in the trial.

Full data results will be presented at an upcoming medical congress and/or published in a peer-reviewed journal, the company said.
 

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

The novel, orally administered calcitonin gene-related peptide (CGRP) antagonist atogepant has met the primary endpoint in a phase 3 trial for migraine prevention, AbbVie, the company developing the drug, has announced.

Top-line results from the ADVANCE trial, which evaluated atogepant 10, 30, and 60 mg, showed all three doses were associated with a significant reduction from baseline in mean monthly migraine days, compared with placebo.

There were also significant improvements in all six secondary endpoints with the two higher doses.

Data from the ADVANCE trial and a previous phase 2/3 trial will be the basis for regulatory submissions in the United States and other countries, AbbVie reported.

Decreased migraine days

The phase 3, multicenter, randomized, double-blind, placebo-controlled, parallel-group trial was designed to evaluate the efficacy, safety, and tolerability of oral atogepant for the prevention of migraine in those who experienced 4-14 migraine days per month.

A total of 910 patients were randomized to one of four treatment groups: 10 mg, 30 mg, or 60 mg of atogepant once daily or placebo. Efficacy analyses were based on the modified intent-to-treat population of 873 patients.

The primary endpoint was change from baseline in mean monthly migraine days during the 12-week treatment period. All atogepant dose groups met the primary endpoint and demonstrated significantly greater decreases in mean monthly migraine days, compared with placebo.

Mean monthly migraine days were reduced by 3.69 days with the 10-mg dose, 3.86 days with the 30-mg dose, and 4.2 days with the 60-mg dose of atogepant, compared with a reduction of 2.48 migraine days in the placebo group (P < .0001, all dose groups vs. placebo).

A key secondary endpoint measured the proportion of patients who achieved at least a 50% reduction in mean monthly migraine days over 12 weeks. This outcome occurred in 55.6% of the 10-mg atogepant group, 58.7% of the 30-mg group, and 60.8% of the 60-mg group, compared with 29% of the placebo group (P < .0001, all dose groups vs. placebo).

Significant improvements

Additional secondary endpoints measured during the 12-week treatment period included change from baseline in mean monthly headache days, mean monthly acute–medication use days, mean monthly performance of daily activities and physical impairment domain scores on the Activity Impairment in Migraine-Diary, and change from baseline in the Migraine-Specific Quality of Life Questionnaire Role Function-Restrictive domain score at week 12. Treatment with the 30-mg and 60-mg doses resulted in significant improvements in all secondary endpoints, and treatment with the 10-mg dose resulted in significant improvements in four of the six secondary endpoints.

No new safety risks were observed when compared with the safety profile of atogepant observed in previous trials, AbbVie said. Serious adverse events occurred in 0.9% of patients in the atogepant 10-mg group versus 0.9% of patients in the placebo group. No patients in the atogepant 30-mg or 60-mg groups experienced a serious adverse event. The most common adverse events (reported in at least 5% of patients and at least one atogepant group and at a rate greater than placebo), across all doses versus placebo, were constipation (6.9%-7.7% vs. 0.5%), nausea (4.4%-6.1% vs. 1.8%), and upper respiratory tract infection (3.9%-5.7% vs. 4.5%).

Most cases of constipation, nausea, and upper respiratory tract infection were mild or moderate in severity and did not lead to discontinuation. There were no hepatic safety issues identified in the trial.

Full data results will be presented at an upcoming medical congress and/or published in a peer-reviewed journal, the company said.
 

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

The novel, orally administered calcitonin gene-related peptide (CGRP) antagonist atogepant has met the primary endpoint in a phase 3 trial for migraine prevention, AbbVie, the company developing the drug, has announced.

Top-line results from the ADVANCE trial, which evaluated atogepant 10, 30, and 60 mg, showed all three doses were associated with a significant reduction from baseline in mean monthly migraine days, compared with placebo.

There were also significant improvements in all six secondary endpoints with the two higher doses.

Data from the ADVANCE trial and a previous phase 2/3 trial will be the basis for regulatory submissions in the United States and other countries, AbbVie reported.

Decreased migraine days

The phase 3, multicenter, randomized, double-blind, placebo-controlled, parallel-group trial was designed to evaluate the efficacy, safety, and tolerability of oral atogepant for the prevention of migraine in those who experienced 4-14 migraine days per month.

A total of 910 patients were randomized to one of four treatment groups: 10 mg, 30 mg, or 60 mg of atogepant once daily or placebo. Efficacy analyses were based on the modified intent-to-treat population of 873 patients.

The primary endpoint was change from baseline in mean monthly migraine days during the 12-week treatment period. All atogepant dose groups met the primary endpoint and demonstrated significantly greater decreases in mean monthly migraine days, compared with placebo.

Mean monthly migraine days were reduced by 3.69 days with the 10-mg dose, 3.86 days with the 30-mg dose, and 4.2 days with the 60-mg dose of atogepant, compared with a reduction of 2.48 migraine days in the placebo group (P < .0001, all dose groups vs. placebo).

A key secondary endpoint measured the proportion of patients who achieved at least a 50% reduction in mean monthly migraine days over 12 weeks. This outcome occurred in 55.6% of the 10-mg atogepant group, 58.7% of the 30-mg group, and 60.8% of the 60-mg group, compared with 29% of the placebo group (P < .0001, all dose groups vs. placebo).

Significant improvements

Additional secondary endpoints measured during the 12-week treatment period included change from baseline in mean monthly headache days, mean monthly acute–medication use days, mean monthly performance of daily activities and physical impairment domain scores on the Activity Impairment in Migraine-Diary, and change from baseline in the Migraine-Specific Quality of Life Questionnaire Role Function-Restrictive domain score at week 12. Treatment with the 30-mg and 60-mg doses resulted in significant improvements in all secondary endpoints, and treatment with the 10-mg dose resulted in significant improvements in four of the six secondary endpoints.

No new safety risks were observed when compared with the safety profile of atogepant observed in previous trials, AbbVie said. Serious adverse events occurred in 0.9% of patients in the atogepant 10-mg group versus 0.9% of patients in the placebo group. No patients in the atogepant 30-mg or 60-mg groups experienced a serious adverse event. The most common adverse events (reported in at least 5% of patients and at least one atogepant group and at a rate greater than placebo), across all doses versus placebo, were constipation (6.9%-7.7% vs. 0.5%), nausea (4.4%-6.1% vs. 1.8%), and upper respiratory tract infection (3.9%-5.7% vs. 4.5%).

Most cases of constipation, nausea, and upper respiratory tract infection were mild or moderate in severity and did not lead to discontinuation. There were no hepatic safety issues identified in the trial.

Full data results will be presented at an upcoming medical congress and/or published in a peer-reviewed journal, the company said.
 

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

Belatedly, the disproportionate impact of COVID-19 on patients of color is getting attention. By now, we’ve read the headlines. Black people in the United States make up about 13% of the population but account for almost three times (34%) as many deaths. This story repeats – in other countries and in other minority communities.

Early detection is critical both to initiate supportive care and to isolate affected individuals and limit spread. Skin manifestations of COVID-19, especially those that occur early in the disease (eg, vesicular eruptions) or have prognostic significance (livedo, retiform purpura, necrosis), are critical to this goal of early recognition.

In this context, a recent systematic literature review looked at all articles describing skin manifestations associated with COVID-19. The investigators identified 46 articles published between March and May 2020 which included a total of 130 clinical images.

The following findings from this study are striking:

• 92% of the published images of COVID-associated skin manifestations were in I-III.
• Only 6% of COVID skin lesions included in the articles were in patients with skin type IV.
• None showed COVID skin lesions in skin types V or VI.
• Only six of the articles reported race and ethnicity demographics. In those, 91% of the patients were White and 9% were Hispanic.

These results reveal a critical lack of representative clinical images of COVID-associated skin manifestations in patients of color. This deficiency is made all the more egregious given the fact that patients of color, including those who are Black, Latinx, and Native American, have been especially hard hit by the COVID-19 pandemic and suffer disproportionate disease-related morbidity and mortality.
 

As the study authors point out, skin manifestations in people of color often differ significantly from findings in White skin (for example, look at the figure depicting the rash typical of Kawasaki disease in a dark-skinned child compared with a light-skinned child). It is not a stretch to suggest that skin manifestations associated with COVID-19 may look very different in darker skin.

These investigators have identified a damning lack of images of COVID-19–associated skin manifestations in patients with darker skin. This isn’t a new phenomenon. Almost half of dermatologists feel that they’ve had insufficient exposure to skin disease in darker skin types. Skin of color remains underrepresented in medical journals.

Like other forms of passive, institutional racism, this deficiency will only be improved if dermatologists and dermatology publications actively seek out COVID-associated skin manifestations in patients of color and prioritize sharing these images. A medical student in the United Kingdom has gotten the ball rolling, compiling a handbook of clinical signs in darker skin types as part of a student-staff partnership at St. George’s Hospital and the University of London. At this time, Mind the Gap is looking for a publisher.

Dr. Lipper is an assistant clinical professor at the University of Vermont, Burlington, and a staff physician in the department of dermatology at Danbury (Conn.) Hospital. He has disclosed no relevant financial relationships.
 

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

Belatedly, the disproportionate impact of COVID-19 on patients of color is getting attention. By now, we’ve read the headlines. Black people in the United States make up about 13% of the population but account for almost three times (34%) as many deaths. This story repeats – in other countries and in other minority communities.

Early detection is critical both to initiate supportive care and to isolate affected individuals and limit spread. Skin manifestations of COVID-19, especially those that occur early in the disease (eg, vesicular eruptions) or have prognostic significance (livedo, retiform purpura, necrosis), are critical to this goal of early recognition.

In this context, a recent systematic literature review looked at all articles describing skin manifestations associated with COVID-19. The investigators identified 46 articles published between March and May 2020 which included a total of 130 clinical images.

The following findings from this study are striking:

• 92% of the published images of COVID-associated skin manifestations were in I-III.
• Only 6% of COVID skin lesions included in the articles were in patients with skin type IV.
• None showed COVID skin lesions in skin types V or VI.
• Only six of the articles reported race and ethnicity demographics. In those, 91% of the patients were White and 9% were Hispanic.

These results reveal a critical lack of representative clinical images of COVID-associated skin manifestations in patients of color. This deficiency is made all the more egregious given the fact that patients of color, including those who are Black, Latinx, and Native American, have been especially hard hit by the COVID-19 pandemic and suffer disproportionate disease-related morbidity and mortality.
 

As the study authors point out, skin manifestations in people of color often differ significantly from findings in White skin (for example, look at the figure depicting the rash typical of Kawasaki disease in a dark-skinned child compared with a light-skinned child). It is not a stretch to suggest that skin manifestations associated with COVID-19 may look very different in darker skin.

These investigators have identified a damning lack of images of COVID-19–associated skin manifestations in patients with darker skin. This isn’t a new phenomenon. Almost half of dermatologists feel that they’ve had insufficient exposure to skin disease in darker skin types. Skin of color remains underrepresented in medical journals.

Like other forms of passive, institutional racism, this deficiency will only be improved if dermatologists and dermatology publications actively seek out COVID-associated skin manifestations in patients of color and prioritize sharing these images. A medical student in the United Kingdom has gotten the ball rolling, compiling a handbook of clinical signs in darker skin types as part of a student-staff partnership at St. George’s Hospital and the University of London. At this time, Mind the Gap is looking for a publisher.

Dr. Lipper is an assistant clinical professor at the University of Vermont, Burlington, and a staff physician in the department of dermatology at Danbury (Conn.) Hospital. He has disclosed no relevant financial relationships.
 

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

Belatedly, the disproportionate impact of COVID-19 on patients of color is getting attention. By now, we’ve read the headlines. Black people in the United States make up about 13% of the population but account for almost three times (34%) as many deaths. This story repeats – in other countries and in other minority communities.

Early detection is critical both to initiate supportive care and to isolate affected individuals and limit spread. Skin manifestations of COVID-19, especially those that occur early in the disease (eg, vesicular eruptions) or have prognostic significance (livedo, retiform purpura, necrosis), are critical to this goal of early recognition.

In this context, a recent systematic literature review looked at all articles describing skin manifestations associated with COVID-19. The investigators identified 46 articles published between March and May 2020 which included a total of 130 clinical images.

The following findings from this study are striking:

• 92% of the published images of COVID-associated skin manifestations were in I-III.
• Only 6% of COVID skin lesions included in the articles were in patients with skin type IV.
• None showed COVID skin lesions in skin types V or VI.
• Only six of the articles reported race and ethnicity demographics. In those, 91% of the patients were White and 9% were Hispanic.

These results reveal a critical lack of representative clinical images of COVID-associated skin manifestations in patients of color. This deficiency is made all the more egregious given the fact that patients of color, including those who are Black, Latinx, and Native American, have been especially hard hit by the COVID-19 pandemic and suffer disproportionate disease-related morbidity and mortality.
 

As the study authors point out, skin manifestations in people of color often differ significantly from findings in White skin (for example, look at the figure depicting the rash typical of Kawasaki disease in a dark-skinned child compared with a light-skinned child). It is not a stretch to suggest that skin manifestations associated with COVID-19 may look very different in darker skin.

These investigators have identified a damning lack of images of COVID-19–associated skin manifestations in patients with darker skin. This isn’t a new phenomenon. Almost half of dermatologists feel that they’ve had insufficient exposure to skin disease in darker skin types. Skin of color remains underrepresented in medical journals.

Like other forms of passive, institutional racism, this deficiency will only be improved if dermatologists and dermatology publications actively seek out COVID-associated skin manifestations in patients of color and prioritize sharing these images. A medical student in the United Kingdom has gotten the ball rolling, compiling a handbook of clinical signs in darker skin types as part of a student-staff partnership at St. George’s Hospital and the University of London. At this time, Mind the Gap is looking for a publisher.

Dr. Lipper is an assistant clinical professor at the University of Vermont, Burlington, and a staff physician in the department of dermatology at Danbury (Conn.) Hospital. He has disclosed no relevant financial relationships.
 

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

Two new long-term studies, one an extension trial and the other an analysis of real-world experience, show that the RNS System direct brain responsive neurostimulator leads to reduction of seizure frequency in most epilepsy patients who had it implanted. Both studies showed that the benefit from the devices increased over time.

That accruing benefit may be because of improved protocols as clinicians gain experience with the device or because of network remodeling that occurs over time as seizures are controlled. “I think it’s both,” said Martha Morrell, MD, a clinical professor of neurology at Stanford (Calif.) University and chief medical officer at NeuroPace, the company that has marketed the device since it gained FDA approval in 2013.

In both studies, the slope of improvement over time was similar, but the real-world study showed greater improvement at the beginning of treatment. “I think the slopes represent physiological changes, but the fact that [the real-world study] starts with better outcomes is, I think, directly attributable to learning. When the long-term study was started in 2004, this had never been done before, and we had to make a highly educated guess about what we should do, and the initial stimulatory parameters were programmed in a way that’s very similar to what was used for movement disorders,” Dr. Morrell said in an interview.

The long-term treatment study appeared online July 20 in the journal Neurology, while the real-world analysis was published July 13 in Epilepsia.
 

An alternative option

Medications can effectively treat some seizures, but 30%-40% of patients must turn to other options for control. Surgery can sometimes be curative, but is not suitable for some patients. Other stimulation devices include vagus nerve stimulation (VNS), which sends pulses from a chest implant to the vagus nerve, reducing epileptic attacks through an unknown mechanism. Deep brain stimulation (DBS) places electrodes that deliver stimulation to the anterior nucleus of the thalamus, which can spread initially localized seizures.

The RNS device consists of a neurostimulator implanted cranially and connected to leads that are placed based on the individual patient’s seizure focus or foci. It also continuously monitors brain activity and delivers stimulation only when its signal suggests the beginning of a seizure.

That capacity for recording is a key benefit because the information can be stored and analyzed, according to Vikram Rao, MD, PhD, a coinvestigator in the real-world trial and an associate professor and the epilepsy division chief at the University of California, San Francisco, which was one of the trial centers. “You know more precisely than we previously did how many seizures a patient is having. Many of our patients are not able to quantify their seizures with perfect accuracy, so we’re better quantifying their seizure burden,” Dr. Rao said in an interview.

The ability to monitor patients can also improve clinical management. Dr. Morrell recounted an elderly patient who for many years has driven 5 hours for appointments. Recently she was able to review his data from the RNS System remotely. She determined that he was doing fine and, after a telephone consultation, told him he didn’t need to come in for a scheduled visit.
 

Real-world analysis

In the real-world analysis, researchers led by Babak Razavi, PhD, and Casey Halpern, MD, at Stanford University conducted a chart review of 150 patients at eight centers who underwent treatment with the RNS system between 2013 and 2018. All patients were followed at least 1 year, with a mean of 2.3 years. Patients had a median of 7.7 disabling seizures per month. The mean value was 52 and the numbers ranged from 0.1 to 3,000. A total of 60% had abnormal brain MRI findings.

At 1 year, subjects achieved a mean 67% decrease in seizure frequency (interquartile range, 50%-94%). At 2 years, that grew to 77%; at 3 or more years, 84%. There was no significant difference in seizure reduction at 1 year according to age, age at epilepsy onset, duration of epilepsy, location of seizure foci, presence of brain MRI abnormalities, prior intracranial monitoring, prior epilepsy surgery, or prior VNS treatment. When patients who underwent a resection at the time of RNS placement were excluded, the results were similar. There were no significant differences in outcome by center.

A total of 11.3% of patients experienced a device-related serious adverse event, and 4% developed infections. The rate of infection was not significantly different between patients who had the neurostimulator and leads implanted alone (3.0%) and patients who had intracranial EEG diagnostic monitoring (ICM) electrodes removed at the same time (6.1%; P = .38).

Although about one-third of the patients who started the long-term study dropped out before completion, most were because the participants moved away from treatment centers, according to Dr. Morrell, and other evidence points squarely to patient satisfaction. “At the end of the battery’s longevity, the neurostimulator needs to be replaced. It’s an outpatient, 45-minute procedure. Over 90% of patients chose to have it replaced. It’s not the answer for everybody, but the substantial majority of patients choose to continue,” she said.
 

Extension trial

The open-label extension trial, led by Dileep Nair, MD, of the Cleveland Clinic Foundation and Dr. Morrell, followed 230 of the 256 patients who participated in 2-year phase 3 study or feasibility studies, extending device usage to 9 years. A total of 162 completed follow-up (mean, 7.5 years). The median reduction of seizure frequency was 58% at the end of year 3, and 75% by year 9 (P < .0001; Wilcoxon signed rank). Although patient population enrichment could have explained this observation, other analyses confirmed that the improvement was real.

Nearly 75% had at least a 50% reduction in seizure frequency; 35% had a 90% or greater reduction in seizure frequency. Some patients (18.4%) had at least a full year with no seizures, and 62% who had a 1-year seizure-free period experienced no seizures at the latest follow-up. Overall, 21% had no seizures in the last 6 months of follow-up.

For those with a seizure-free period of more than 1 year, the average duration was 3.2 years (range, 1.04-9.6 years). There was no difference in response among patients based on previous antiseizure medication use or previous epilepsy surgery, VNS treatment, or intracranial monitoring, and there were no differences by patient age at enrollment, age of seizure onset, brain imaging abnormality, seizure onset locality, or number of foci.

The researchers noted improvement in overall Quality of Life in Epilepsy Inventory–89 scores at 1 year (mean, +3.2; P < .0001), which continued through year 9 (mean, +1.9; P < .05). Improvements were also seen in epilepsy targeted (mean, +4.5; P < .001) and cognitive domains (mean, +2.5; P = .005). Risk of infection was 4.1% per procedure, and 12.1% of subjects overall experienced a serious device-related implant infection. Of 35 infections, 16 led to device removal.

The extension study was funded by NeuroPace. NeuroPace supported data entry and institutional review board submission for the real-world trial. Dr. Morrell owns stock and is an employee of NeuroPace. Dr Rao has received support from and/or consulted for NeuroPace.

SOURCE: Nair DR et al. Neurology. 2020 Jul 20. doi: 10.1212/WNL.0000000000010154. Razavi B et al. Epilepsia. 2020 Jul 13. doi: 10.1111/epi.16593.

Two new long-term studies, one an extension trial and the other an analysis of real-world experience, show that the RNS System direct brain responsive neurostimulator leads to reduction of seizure frequency in most epilepsy patients who had it implanted. Both studies showed that the benefit from the devices increased over time.

That accruing benefit may be because of improved protocols as clinicians gain experience with the device or because of network remodeling that occurs over time as seizures are controlled. “I think it’s both,” said Martha Morrell, MD, a clinical professor of neurology at Stanford (Calif.) University and chief medical officer at NeuroPace, the company that has marketed the device since it gained FDA approval in 2013.

In both studies, the slope of improvement over time was similar, but the real-world study showed greater improvement at the beginning of treatment. “I think the slopes represent physiological changes, but the fact that [the real-world study] starts with better outcomes is, I think, directly attributable to learning. When the long-term study was started in 2004, this had never been done before, and we had to make a highly educated guess about what we should do, and the initial stimulatory parameters were programmed in a way that’s very similar to what was used for movement disorders,” Dr. Morrell said in an interview.

The long-term treatment study appeared online July 20 in the journal Neurology, while the real-world analysis was published July 13 in Epilepsia.
 

An alternative option

Medications can effectively treat some seizures, but 30%-40% of patients must turn to other options for control. Surgery can sometimes be curative, but is not suitable for some patients. Other stimulation devices include vagus nerve stimulation (VNS), which sends pulses from a chest implant to the vagus nerve, reducing epileptic attacks through an unknown mechanism. Deep brain stimulation (DBS) places electrodes that deliver stimulation to the anterior nucleus of the thalamus, which can spread initially localized seizures.

The RNS device consists of a neurostimulator implanted cranially and connected to leads that are placed based on the individual patient’s seizure focus or foci. It also continuously monitors brain activity and delivers stimulation only when its signal suggests the beginning of a seizure.

That capacity for recording is a key benefit because the information can be stored and analyzed, according to Vikram Rao, MD, PhD, a coinvestigator in the real-world trial and an associate professor and the epilepsy division chief at the University of California, San Francisco, which was one of the trial centers. “You know more precisely than we previously did how many seizures a patient is having. Many of our patients are not able to quantify their seizures with perfect accuracy, so we’re better quantifying their seizure burden,” Dr. Rao said in an interview.

The ability to monitor patients can also improve clinical management. Dr. Morrell recounted an elderly patient who for many years has driven 5 hours for appointments. Recently she was able to review his data from the RNS System remotely. She determined that he was doing fine and, after a telephone consultation, told him he didn’t need to come in for a scheduled visit.
 

Real-world analysis

In the real-world analysis, researchers led by Babak Razavi, PhD, and Casey Halpern, MD, at Stanford University conducted a chart review of 150 patients at eight centers who underwent treatment with the RNS system between 2013 and 2018. All patients were followed at least 1 year, with a mean of 2.3 years. Patients had a median of 7.7 disabling seizures per month. The mean value was 52 and the numbers ranged from 0.1 to 3,000. A total of 60% had abnormal brain MRI findings.

At 1 year, subjects achieved a mean 67% decrease in seizure frequency (interquartile range, 50%-94%). At 2 years, that grew to 77%; at 3 or more years, 84%. There was no significant difference in seizure reduction at 1 year according to age, age at epilepsy onset, duration of epilepsy, location of seizure foci, presence of brain MRI abnormalities, prior intracranial monitoring, prior epilepsy surgery, or prior VNS treatment. When patients who underwent a resection at the time of RNS placement were excluded, the results were similar. There were no significant differences in outcome by center.

A total of 11.3% of patients experienced a device-related serious adverse event, and 4% developed infections. The rate of infection was not significantly different between patients who had the neurostimulator and leads implanted alone (3.0%) and patients who had intracranial EEG diagnostic monitoring (ICM) electrodes removed at the same time (6.1%; P = .38).

Although about one-third of the patients who started the long-term study dropped out before completion, most were because the participants moved away from treatment centers, according to Dr. Morrell, and other evidence points squarely to patient satisfaction. “At the end of the battery’s longevity, the neurostimulator needs to be replaced. It’s an outpatient, 45-minute procedure. Over 90% of patients chose to have it replaced. It’s not the answer for everybody, but the substantial majority of patients choose to continue,” she said.
 

Extension trial

The open-label extension trial, led by Dileep Nair, MD, of the Cleveland Clinic Foundation and Dr. Morrell, followed 230 of the 256 patients who participated in 2-year phase 3 study or feasibility studies, extending device usage to 9 years. A total of 162 completed follow-up (mean, 7.5 years). The median reduction of seizure frequency was 58% at the end of year 3, and 75% by year 9 (P < .0001; Wilcoxon signed rank). Although patient population enrichment could have explained this observation, other analyses confirmed that the improvement was real.

Nearly 75% had at least a 50% reduction in seizure frequency; 35% had a 90% or greater reduction in seizure frequency. Some patients (18.4%) had at least a full year with no seizures, and 62% who had a 1-year seizure-free period experienced no seizures at the latest follow-up. Overall, 21% had no seizures in the last 6 months of follow-up.

For those with a seizure-free period of more than 1 year, the average duration was 3.2 years (range, 1.04-9.6 years). There was no difference in response among patients based on previous antiseizure medication use or previous epilepsy surgery, VNS treatment, or intracranial monitoring, and there were no differences by patient age at enrollment, age of seizure onset, brain imaging abnormality, seizure onset locality, or number of foci.

The researchers noted improvement in overall Quality of Life in Epilepsy Inventory–89 scores at 1 year (mean, +3.2; P < .0001), which continued through year 9 (mean, +1.9; P < .05). Improvements were also seen in epilepsy targeted (mean, +4.5; P < .001) and cognitive domains (mean, +2.5; P = .005). Risk of infection was 4.1% per procedure, and 12.1% of subjects overall experienced a serious device-related implant infection. Of 35 infections, 16 led to device removal.

The extension study was funded by NeuroPace. NeuroPace supported data entry and institutional review board submission for the real-world trial. Dr. Morrell owns stock and is an employee of NeuroPace. Dr Rao has received support from and/or consulted for NeuroPace.

SOURCE: Nair DR et al. Neurology. 2020 Jul 20. doi: 10.1212/WNL.0000000000010154. Razavi B et al. Epilepsia. 2020 Jul 13. doi: 10.1111/epi.16593.

Two new long-term studies, one an extension trial and the other an analysis of real-world experience, show that the RNS System direct brain responsive neurostimulator leads to reduction of seizure frequency in most epilepsy patients who had it implanted. Both studies showed that the benefit from the devices increased over time.

That accruing benefit may be because of improved protocols as clinicians gain experience with the device or because of network remodeling that occurs over time as seizures are controlled. “I think it’s both,” said Martha Morrell, MD, a clinical professor of neurology at Stanford (Calif.) University and chief medical officer at NeuroPace, the company that has marketed the device since it gained FDA approval in 2013.

In both studies, the slope of improvement over time was similar, but the real-world study showed greater improvement at the beginning of treatment. “I think the slopes represent physiological changes, but the fact that [the real-world study] starts with better outcomes is, I think, directly attributable to learning. When the long-term study was started in 2004, this had never been done before, and we had to make a highly educated guess about what we should do, and the initial stimulatory parameters were programmed in a way that’s very similar to what was used for movement disorders,” Dr. Morrell said in an interview.

The long-term treatment study appeared online July 20 in the journal Neurology, while the real-world analysis was published July 13 in Epilepsia.
 

An alternative option

Medications can effectively treat some seizures, but 30%-40% of patients must turn to other options for control. Surgery can sometimes be curative, but is not suitable for some patients. Other stimulation devices include vagus nerve stimulation (VNS), which sends pulses from a chest implant to the vagus nerve, reducing epileptic attacks through an unknown mechanism. Deep brain stimulation (DBS) places electrodes that deliver stimulation to the anterior nucleus of the thalamus, which can spread initially localized seizures.

The RNS device consists of a neurostimulator implanted cranially and connected to leads that are placed based on the individual patient’s seizure focus or foci. It also continuously monitors brain activity and delivers stimulation only when its signal suggests the beginning of a seizure.

That capacity for recording is a key benefit because the information can be stored and analyzed, according to Vikram Rao, MD, PhD, a coinvestigator in the real-world trial and an associate professor and the epilepsy division chief at the University of California, San Francisco, which was one of the trial centers. “You know more precisely than we previously did how many seizures a patient is having. Many of our patients are not able to quantify their seizures with perfect accuracy, so we’re better quantifying their seizure burden,” Dr. Rao said in an interview.

The ability to monitor patients can also improve clinical management. Dr. Morrell recounted an elderly patient who for many years has driven 5 hours for appointments. Recently she was able to review his data from the RNS System remotely. She determined that he was doing fine and, after a telephone consultation, told him he didn’t need to come in for a scheduled visit.
 

Real-world analysis

In the real-world analysis, researchers led by Babak Razavi, PhD, and Casey Halpern, MD, at Stanford University conducted a chart review of 150 patients at eight centers who underwent treatment with the RNS system between 2013 and 2018. All patients were followed at least 1 year, with a mean of 2.3 years. Patients had a median of 7.7 disabling seizures per month. The mean value was 52 and the numbers ranged from 0.1 to 3,000. A total of 60% had abnormal brain MRI findings.

At 1 year, subjects achieved a mean 67% decrease in seizure frequency (interquartile range, 50%-94%). At 2 years, that grew to 77%; at 3 or more years, 84%. There was no significant difference in seizure reduction at 1 year according to age, age at epilepsy onset, duration of epilepsy, location of seizure foci, presence of brain MRI abnormalities, prior intracranial monitoring, prior epilepsy surgery, or prior VNS treatment. When patients who underwent a resection at the time of RNS placement were excluded, the results were similar. There were no significant differences in outcome by center.

A total of 11.3% of patients experienced a device-related serious adverse event, and 4% developed infections. The rate of infection was not significantly different between patients who had the neurostimulator and leads implanted alone (3.0%) and patients who had intracranial EEG diagnostic monitoring (ICM) electrodes removed at the same time (6.1%; P = .38).

Although about one-third of the patients who started the long-term study dropped out before completion, most were because the participants moved away from treatment centers, according to Dr. Morrell, and other evidence points squarely to patient satisfaction. “At the end of the battery’s longevity, the neurostimulator needs to be replaced. It’s an outpatient, 45-minute procedure. Over 90% of patients chose to have it replaced. It’s not the answer for everybody, but the substantial majority of patients choose to continue,” she said.
 

Extension trial

The open-label extension trial, led by Dileep Nair, MD, of the Cleveland Clinic Foundation and Dr. Morrell, followed 230 of the 256 patients who participated in 2-year phase 3 study or feasibility studies, extending device usage to 9 years. A total of 162 completed follow-up (mean, 7.5 years). The median reduction of seizure frequency was 58% at the end of year 3, and 75% by year 9 (P < .0001; Wilcoxon signed rank). Although patient population enrichment could have explained this observation, other analyses confirmed that the improvement was real.

Nearly 75% had at least a 50% reduction in seizure frequency; 35% had a 90% or greater reduction in seizure frequency. Some patients (18.4%) had at least a full year with no seizures, and 62% who had a 1-year seizure-free period experienced no seizures at the latest follow-up. Overall, 21% had no seizures in the last 6 months of follow-up.

For those with a seizure-free period of more than 1 year, the average duration was 3.2 years (range, 1.04-9.6 years). There was no difference in response among patients based on previous antiseizure medication use or previous epilepsy surgery, VNS treatment, or intracranial monitoring, and there were no differences by patient age at enrollment, age of seizure onset, brain imaging abnormality, seizure onset locality, or number of foci.

The researchers noted improvement in overall Quality of Life in Epilepsy Inventory–89 scores at 1 year (mean, +3.2; P < .0001), which continued through year 9 (mean, +1.9; P < .05). Improvements were also seen in epilepsy targeted (mean, +4.5; P < .001) and cognitive domains (mean, +2.5; P = .005). Risk of infection was 4.1% per procedure, and 12.1% of subjects overall experienced a serious device-related implant infection. Of 35 infections, 16 led to device removal.

The extension study was funded by NeuroPace. NeuroPace supported data entry and institutional review board submission for the real-world trial. Dr. Morrell owns stock and is an employee of NeuroPace. Dr Rao has received support from and/or consulted for NeuroPace.

SOURCE: Nair DR et al. Neurology. 2020 Jul 20. doi: 10.1212/WNL.0000000000010154. Razavi B et al. Epilepsia. 2020 Jul 13. doi: 10.1111/epi.16593.

LEUVEN, Belgium — A 54-year-old woman has suffered the delusion of thinking she is a chicken for 24 hours. This very rare condition, known as zoanthropy, in which people think they are an animal is often not recognised, say researchers from the University of Leuven.

Zoanthropy can include people believing they are, or behaving like, any kind of animal: from a dog, to a lion or tiger, crocodile, snake, or bee.

It’s important to recognise this as a potential symptom of something serious, say the researchers in the July issue of the Belgian Journal of Psychiatry, Tijdschrift voor Psychiatrie.

The delusion can be a sign of an underlying psychiatric disorder, or it can be secondary to structural or functional abnormalities in the brain.

“Additional investigations with brain imaging and electroencephalogram are therefore advised,” say the authors. 
 

Psychiatrists Need to Be Aware That Clinical Zoanthropy Exists

In their paper, they describe the case of the woman who briefly thought she was a chicken, which was followed by her having a generalized epileptic seizure.

“Clinically, we saw a lady who perspired profusely, trembled, blew up her cheeks, and ... seemed to imitate a chicken, [making noises] like clucking, cackling, and crowing like a rooster,” they say.

“After about 10 minutes she seemed to tighten her muscles for a few seconds, her face turned red and for a short time she didn’t react. These symptoms repeated themselves at intervals of a few minutes [and her] consciousness was fluctuating,” with the patient “disoriented in time and space.”

Lead author Dr Athena Beckers of University Psychiatric Centre, KU Leuven, Belgium, said in an interview with MediQuality: “With only 56 case descriptions in the medical literature from 1850 to the present day, the condition is rare. It amounts to about one description every 3 years.

“We suspect, however, that the delusion is not always noticed: the patient shows bizarre behaviour or makes animal sounds, it is probably often catalogued under the general term ‘psychosis’.”

Dr Beckers adds that it is important that the symptoms are recognised, because of the possible underlying causes which can include epilepsy. So this might require a different or complementary treatment “with, for example, antiepileptic drugs”.

“I myself have only seen this type of delusion once, but I ... heard anecdotal stories from other patients whose family member, for example with schizophrenia, sometimes thought he was a cow [during] ... a psychosis.

“After the publication of my article I was also contacted by someone who told me they had experienced the same thing 30 years ago – he thought he was a chicken.

“I think it’s a good thing that we psychiatrists are aware of the fact that clinical zoanthropy exists and may require additional research,” she observed.

Fortunately, this woman’s experience ended well. After about one year of disability, the patient was able to return to work progressively. Her mood remained stable and there were no more psychotic symptoms or any indication of epileptic episodes.
 

Such Delusions Are Rare 

Dr Georges Otte, a recently retired neuropsychiatrist who formerly worked at Ghent University, Belgium, gave his thoughts to Mediquality: “The interface between neurology and psychiatry ... is a fertile meadow on which many crops thrive. But it is in the darkest corners of psychosis that one finds the most bizarre and also rarest excesses.”

There are a number of delusions of identity, said Dr Otte.

These include Cotard’s syndrome, a rare condition marked by the false belief that the person or their body parts are dead, dying, or don’t exist, or Capgras delusion, where the affected person believes that a spouse or close family member has been replaced with an imposter. Delusions can also occur as a result of substance abuse, for example after using psilocybin (magic mushrooms), he added.

“Delusions in which patients are convinced of ‘shape shifting’ (man to animal) are quite rare,” Dr Otte observed.

“In the literature we know that lycanthropy [a person thinks he or she is turning into a werewolf],” has been reported, and has “apparently inspired many authors of horror stories,” he added.

“But it’s not every day that as a psychiatrist, you will encounter such an extreme psychotic depersonalization as someone turning into a chicken.”
 

This article first appeared on Medscape.com.

LEUVEN, Belgium — A 54-year-old woman has suffered the delusion of thinking she is a chicken for 24 hours. This very rare condition, known as zoanthropy, in which people think they are an animal is often not recognised, say researchers from the University of Leuven.

Zoanthropy can include people believing they are, or behaving like, any kind of animal: from a dog, to a lion or tiger, crocodile, snake, or bee.

It’s important to recognise this as a potential symptom of something serious, say the researchers in the July issue of the Belgian Journal of Psychiatry, Tijdschrift voor Psychiatrie.

The delusion can be a sign of an underlying psychiatric disorder, or it can be secondary to structural or functional abnormalities in the brain.

“Additional investigations with brain imaging and electroencephalogram are therefore advised,” say the authors. 
 

Psychiatrists Need to Be Aware That Clinical Zoanthropy Exists

In their paper, they describe the case of the woman who briefly thought she was a chicken, which was followed by her having a generalized epileptic seizure.

“Clinically, we saw a lady who perspired profusely, trembled, blew up her cheeks, and ... seemed to imitate a chicken, [making noises] like clucking, cackling, and crowing like a rooster,” they say.

“After about 10 minutes she seemed to tighten her muscles for a few seconds, her face turned red and for a short time she didn’t react. These symptoms repeated themselves at intervals of a few minutes [and her] consciousness was fluctuating,” with the patient “disoriented in time and space.”

Lead author Dr Athena Beckers of University Psychiatric Centre, KU Leuven, Belgium, said in an interview with MediQuality: “With only 56 case descriptions in the medical literature from 1850 to the present day, the condition is rare. It amounts to about one description every 3 years.

“We suspect, however, that the delusion is not always noticed: the patient shows bizarre behaviour or makes animal sounds, it is probably often catalogued under the general term ‘psychosis’.”

Dr Beckers adds that it is important that the symptoms are recognised, because of the possible underlying causes which can include epilepsy. So this might require a different or complementary treatment “with, for example, antiepileptic drugs”.

“I myself have only seen this type of delusion once, but I ... heard anecdotal stories from other patients whose family member, for example with schizophrenia, sometimes thought he was a cow [during] ... a psychosis.

“After the publication of my article I was also contacted by someone who told me they had experienced the same thing 30 years ago – he thought he was a chicken.

“I think it’s a good thing that we psychiatrists are aware of the fact that clinical zoanthropy exists and may require additional research,” she observed.

Fortunately, this woman’s experience ended well. After about one year of disability, the patient was able to return to work progressively. Her mood remained stable and there were no more psychotic symptoms or any indication of epileptic episodes.
 

Such Delusions Are Rare 

Dr Georges Otte, a recently retired neuropsychiatrist who formerly worked at Ghent University, Belgium, gave his thoughts to Mediquality: “The interface between neurology and psychiatry ... is a fertile meadow on which many crops thrive. But it is in the darkest corners of psychosis that one finds the most bizarre and also rarest excesses.”

There are a number of delusions of identity, said Dr Otte.

These include Cotard’s syndrome, a rare condition marked by the false belief that the person or their body parts are dead, dying, or don’t exist, or Capgras delusion, where the affected person believes that a spouse or close family member has been replaced with an imposter. Delusions can also occur as a result of substance abuse, for example after using psilocybin (magic mushrooms), he added.

“Delusions in which patients are convinced of ‘shape shifting’ (man to animal) are quite rare,” Dr Otte observed.

“In the literature we know that lycanthropy [a person thinks he or she is turning into a werewolf],” has been reported, and has “apparently inspired many authors of horror stories,” he added.

“But it’s not every day that as a psychiatrist, you will encounter such an extreme psychotic depersonalization as someone turning into a chicken.”
 

This article first appeared on Medscape.com.

LEUVEN, Belgium — A 54-year-old woman has suffered the delusion of thinking she is a chicken for 24 hours. This very rare condition, known as zoanthropy, in which people think they are an animal is often not recognised, say researchers from the University of Leuven.

Zoanthropy can include people believing they are, or behaving like, any kind of animal: from a dog, to a lion or tiger, crocodile, snake, or bee.

It’s important to recognise this as a potential symptom of something serious, say the researchers in the July issue of the Belgian Journal of Psychiatry, Tijdschrift voor Psychiatrie.

The delusion can be a sign of an underlying psychiatric disorder, or it can be secondary to structural or functional abnormalities in the brain.

“Additional investigations with brain imaging and electroencephalogram are therefore advised,” say the authors. 
 

Psychiatrists Need to Be Aware That Clinical Zoanthropy Exists

In their paper, they describe the case of the woman who briefly thought she was a chicken, which was followed by her having a generalized epileptic seizure.

“Clinically, we saw a lady who perspired profusely, trembled, blew up her cheeks, and ... seemed to imitate a chicken, [making noises] like clucking, cackling, and crowing like a rooster,” they say.

“After about 10 minutes she seemed to tighten her muscles for a few seconds, her face turned red and for a short time she didn’t react. These symptoms repeated themselves at intervals of a few minutes [and her] consciousness was fluctuating,” with the patient “disoriented in time and space.”

Lead author Dr Athena Beckers of University Psychiatric Centre, KU Leuven, Belgium, said in an interview with MediQuality: “With only 56 case descriptions in the medical literature from 1850 to the present day, the condition is rare. It amounts to about one description every 3 years.

“We suspect, however, that the delusion is not always noticed: the patient shows bizarre behaviour or makes animal sounds, it is probably often catalogued under the general term ‘psychosis’.”

Dr Beckers adds that it is important that the symptoms are recognised, because of the possible underlying causes which can include epilepsy. So this might require a different or complementary treatment “with, for example, antiepileptic drugs”.

“I myself have only seen this type of delusion once, but I ... heard anecdotal stories from other patients whose family member, for example with schizophrenia, sometimes thought he was a cow [during] ... a psychosis.

“After the publication of my article I was also contacted by someone who told me they had experienced the same thing 30 years ago – he thought he was a chicken.

“I think it’s a good thing that we psychiatrists are aware of the fact that clinical zoanthropy exists and may require additional research,” she observed.

Fortunately, this woman’s experience ended well. After about one year of disability, the patient was able to return to work progressively. Her mood remained stable and there were no more psychotic symptoms or any indication of epileptic episodes.
 

Such Delusions Are Rare 

Dr Georges Otte, a recently retired neuropsychiatrist who formerly worked at Ghent University, Belgium, gave his thoughts to Mediquality: “The interface between neurology and psychiatry ... is a fertile meadow on which many crops thrive. But it is in the darkest corners of psychosis that one finds the most bizarre and also rarest excesses.”

There are a number of delusions of identity, said Dr Otte.

These include Cotard’s syndrome, a rare condition marked by the false belief that the person or their body parts are dead, dying, or don’t exist, or Capgras delusion, where the affected person believes that a spouse or close family member has been replaced with an imposter. Delusions can also occur as a result of substance abuse, for example after using psilocybin (magic mushrooms), he added.

“Delusions in which patients are convinced of ‘shape shifting’ (man to animal) are quite rare,” Dr Otte observed.

“In the literature we know that lycanthropy [a person thinks he or she is turning into a werewolf],” has been reported, and has “apparently inspired many authors of horror stories,” he added.

“But it’s not every day that as a psychiatrist, you will encounter such an extreme psychotic depersonalization as someone turning into a chicken.”
 

This article first appeared on Medscape.com.

An erythematous rash was the most common cutaneous manifestation in patients with COVID-19, followed by chilblain-like lesions and urticaria-like lesions in a systematic review of mostly European studies.

Qing Zhao, MD, Xiaokai Fang, MD, and their colleagues at the Shandong Provincial Hospital for Skin Diseases & Shandong Provincial Institute of Dermatology and Venereology, in Jinan, China, reported the results of a literature review of 44 articles published through May 2020 that included 507 patients with cutaneous manifestations of COVID-19. The review was published in the Journal of The European Academy of Dermatology and Venereology.

Nearly all of the patients (96%) were from Europe, and more than half were women (60%), with an average age of 49 years. Most patients had multiple skin symptoms, with the most common being erythema (44%), chilblain-like lesions (20%), urticaria-like lesions (16%), vesicular manifestations (13%), livedo/necrosis (6%), and petechiae (almost 2%). The authors described erythema as being present in specific sites, such as the trunk, extremities, flexural regions, face, and mucous membranes. Slightly less than half of all patients had significant pruritus.

Data on systemic COVID-19 symptoms were available for 431 patients and included fever in about two-thirds of patients and cough in almost 70%, with dyspnea in almost half of patients. Almost 60% had fatigue, and almost 60% had asthenia. Information about the onset of skin symptoms was available in 88 patients; of these patients, lesions were seen an average of almost 10 days after systemic symptoms appeared and, in almost 15%, were the first symptoms noted.

Histopathologic exams were done for only 23 patients and, in all cases, showed “inflammatory features without specific pathological changes, such as lymphocyte infiltration.” In one study, reverse transcription polymerase chain reaction testing of skin biopsy specimens tested negative for SARS-CoV-2.

Expression of ACE2, the receptor of SARS-CoV-2, in the skin was evaluated in six of the studies. “Higher ACE2 expression was identified in keratinocytes, mainly in differentiating keratinocytes and basal cells compared to the other cells of skin tissues,” the authors wrote. These results were confirmed with immunohistochemistry, which, they said, found “ACE2-positive keratinocytes in the stratum basal, the stratum spinosum, and the stratum granulosum of epiderma.” They added that this provides evidence “for percutaneous infection or the entry of virus into patients through skin tissues,” but cautioned that more research is needed.

The authors acknowledged that there are still many unanswered questions about COVID-19, and that more clinical data and research are needed, to improve the understanding of the cutaneous manifestations associated with COVID-19.

Pathogenesis of different cutaneous manifestations may be different, Dr. Femia said. For example, urticaria and morbilliform eruption were described by the authors of the review as more benign eruptions, but pathogenesis may differ from that of so-called COVID toes and from the pathogenesis of purpura and ulcerations seen in patients with more severe disease, she noted. It is plausible, she added, that purpura and ulcerations may be a “direct invasion of SARS-CoV-2 into endothelial cells,” which creates secondary processes “that ultimately destroy the skin.”

Urticaria and morbilliform eruptions, on the other hand, “are more simply that the immune system is recognizing COVID, and in doing so, is also recognizing some antigens in the skin and creating a hypersensitive response to the skin” and has “nothing to do with the SARS-CoV-2 virus actually being in that location,” she said.

It is important to differentiate between patients who have skin manifestations attributed to COVID-19 and those with manifestations independent of COVID-19, which is difficult, Dr. Femia noted. A patient with COVID-19 and a cutaneous manifestation may be having a reaction to a medication. “It’s important to have a critical eye and to remember that, when we see these manifestations, we should always be investigating whether there was an alternative cause so that we can better learn what exactly we should be attributing to this infection,” she said

Adam Friedman, MD, professor and interim chair of dermatology at George Washington University, Washington, said the authors of the review had presented interesting work, but made some “assumptions that need to be proven.” Dr. Friedman also was not involved in the research, but agreed in an interview with the assessment that it is unlikely SARS-CoV-2 would penetrate the skin. While some viruses – such as the poxvirus that causes molluscum contagiosum and the herpes simplex virus – invade keratinocytes specifically, there is a particular clinical phenotype that results that is associated with changes in the epidermis. However, “the skin manifestations of COVID-19 do not fit with direct skin invasion, [but] rather the immune response to systemic disease,” he said.

“[I]n terms of systemic invasion through the skin, it is possible, but this study certainly doesn’t show that. The presence/expression of ACE2 in the epidermis doesn’t translate to route of infection,” Dr. Friedman said..

The study received financial support from Shandong First Medical University, the Innovation Project of Shandong Academy of Medical Sciences and the Shandong Province Taishan Scholar Project. The authors report no relevant financial disclosures. Dr. Femia and Dr. Friedman had no relevant financial disclosures.

SOURCE: Zhao Q et al. J Eur Acad Dermatol Venereol. 2020 Jun 28. doi: 10.1111/jdv.16778.

An erythematous rash was the most common cutaneous manifestation in patients with COVID-19, followed by chilblain-like lesions and urticaria-like lesions in a systematic review of mostly European studies.

Qing Zhao, MD, Xiaokai Fang, MD, and their colleagues at the Shandong Provincial Hospital for Skin Diseases & Shandong Provincial Institute of Dermatology and Venereology, in Jinan, China, reported the results of a literature review of 44 articles published through May 2020 that included 507 patients with cutaneous manifestations of COVID-19. The review was published in the Journal of The European Academy of Dermatology and Venereology.

Nearly all of the patients (96%) were from Europe, and more than half were women (60%), with an average age of 49 years. Most patients had multiple skin symptoms, with the most common being erythema (44%), chilblain-like lesions (20%), urticaria-like lesions (16%), vesicular manifestations (13%), livedo/necrosis (6%), and petechiae (almost 2%). The authors described erythema as being present in specific sites, such as the trunk, extremities, flexural regions, face, and mucous membranes. Slightly less than half of all patients had significant pruritus.

Data on systemic COVID-19 symptoms were available for 431 patients and included fever in about two-thirds of patients and cough in almost 70%, with dyspnea in almost half of patients. Almost 60% had fatigue, and almost 60% had asthenia. Information about the onset of skin symptoms was available in 88 patients; of these patients, lesions were seen an average of almost 10 days after systemic symptoms appeared and, in almost 15%, were the first symptoms noted.

Histopathologic exams were done for only 23 patients and, in all cases, showed “inflammatory features without specific pathological changes, such as lymphocyte infiltration.” In one study, reverse transcription polymerase chain reaction testing of skin biopsy specimens tested negative for SARS-CoV-2.

Expression of ACE2, the receptor of SARS-CoV-2, in the skin was evaluated in six of the studies. “Higher ACE2 expression was identified in keratinocytes, mainly in differentiating keratinocytes and basal cells compared to the other cells of skin tissues,” the authors wrote. These results were confirmed with immunohistochemistry, which, they said, found “ACE2-positive keratinocytes in the stratum basal, the stratum spinosum, and the stratum granulosum of epiderma.” They added that this provides evidence “for percutaneous infection or the entry of virus into patients through skin tissues,” but cautioned that more research is needed.

The authors acknowledged that there are still many unanswered questions about COVID-19, and that more clinical data and research are needed, to improve the understanding of the cutaneous manifestations associated with COVID-19.

Pathogenesis of different cutaneous manifestations may be different, Dr. Femia said. For example, urticaria and morbilliform eruption were described by the authors of the review as more benign eruptions, but pathogenesis may differ from that of so-called COVID toes and from the pathogenesis of purpura and ulcerations seen in patients with more severe disease, she noted. It is plausible, she added, that purpura and ulcerations may be a “direct invasion of SARS-CoV-2 into endothelial cells,” which creates secondary processes “that ultimately destroy the skin.”

Urticaria and morbilliform eruptions, on the other hand, “are more simply that the immune system is recognizing COVID, and in doing so, is also recognizing some antigens in the skin and creating a hypersensitive response to the skin” and has “nothing to do with the SARS-CoV-2 virus actually being in that location,” she said.

It is important to differentiate between patients who have skin manifestations attributed to COVID-19 and those with manifestations independent of COVID-19, which is difficult, Dr. Femia noted. A patient with COVID-19 and a cutaneous manifestation may be having a reaction to a medication. “It’s important to have a critical eye and to remember that, when we see these manifestations, we should always be investigating whether there was an alternative cause so that we can better learn what exactly we should be attributing to this infection,” she said

Adam Friedman, MD, professor and interim chair of dermatology at George Washington University, Washington, said the authors of the review had presented interesting work, but made some “assumptions that need to be proven.” Dr. Friedman also was not involved in the research, but agreed in an interview with the assessment that it is unlikely SARS-CoV-2 would penetrate the skin. While some viruses – such as the poxvirus that causes molluscum contagiosum and the herpes simplex virus – invade keratinocytes specifically, there is a particular clinical phenotype that results that is associated with changes in the epidermis. However, “the skin manifestations of COVID-19 do not fit with direct skin invasion, [but] rather the immune response to systemic disease,” he said.

“[I]n terms of systemic invasion through the skin, it is possible, but this study certainly doesn’t show that. The presence/expression of ACE2 in the epidermis doesn’t translate to route of infection,” Dr. Friedman said..

The study received financial support from Shandong First Medical University, the Innovation Project of Shandong Academy of Medical Sciences and the Shandong Province Taishan Scholar Project. The authors report no relevant financial disclosures. Dr. Femia and Dr. Friedman had no relevant financial disclosures.

SOURCE: Zhao Q et al. J Eur Acad Dermatol Venereol. 2020 Jun 28. doi: 10.1111/jdv.16778.

An erythematous rash was the most common cutaneous manifestation in patients with COVID-19, followed by chilblain-like lesions and urticaria-like lesions in a systematic review of mostly European studies.

Qing Zhao, MD, Xiaokai Fang, MD, and their colleagues at the Shandong Provincial Hospital for Skin Diseases & Shandong Provincial Institute of Dermatology and Venereology, in Jinan, China, reported the results of a literature review of 44 articles published through May 2020 that included 507 patients with cutaneous manifestations of COVID-19. The review was published in the Journal of The European Academy of Dermatology and Venereology.

Nearly all of the patients (96%) were from Europe, and more than half were women (60%), with an average age of 49 years. Most patients had multiple skin symptoms, with the most common being erythema (44%), chilblain-like lesions (20%), urticaria-like lesions (16%), vesicular manifestations (13%), livedo/necrosis (6%), and petechiae (almost 2%). The authors described erythema as being present in specific sites, such as the trunk, extremities, flexural regions, face, and mucous membranes. Slightly less than half of all patients had significant pruritus.

Data on systemic COVID-19 symptoms were available for 431 patients and included fever in about two-thirds of patients and cough in almost 70%, with dyspnea in almost half of patients. Almost 60% had fatigue, and almost 60% had asthenia. Information about the onset of skin symptoms was available in 88 patients; of these patients, lesions were seen an average of almost 10 days after systemic symptoms appeared and, in almost 15%, were the first symptoms noted.

Histopathologic exams were done for only 23 patients and, in all cases, showed “inflammatory features without specific pathological changes, such as lymphocyte infiltration.” In one study, reverse transcription polymerase chain reaction testing of skin biopsy specimens tested negative for SARS-CoV-2.

Expression of ACE2, the receptor of SARS-CoV-2, in the skin was evaluated in six of the studies. “Higher ACE2 expression was identified in keratinocytes, mainly in differentiating keratinocytes and basal cells compared to the other cells of skin tissues,” the authors wrote. These results were confirmed with immunohistochemistry, which, they said, found “ACE2-positive keratinocytes in the stratum basal, the stratum spinosum, and the stratum granulosum of epiderma.” They added that this provides evidence “for percutaneous infection or the entry of virus into patients through skin tissues,” but cautioned that more research is needed.

The authors acknowledged that there are still many unanswered questions about COVID-19, and that more clinical data and research are needed, to improve the understanding of the cutaneous manifestations associated with COVID-19.

Pathogenesis of different cutaneous manifestations may be different, Dr. Femia said. For example, urticaria and morbilliform eruption were described by the authors of the review as more benign eruptions, but pathogenesis may differ from that of so-called COVID toes and from the pathogenesis of purpura and ulcerations seen in patients with more severe disease, she noted. It is plausible, she added, that purpura and ulcerations may be a “direct invasion of SARS-CoV-2 into endothelial cells,” which creates secondary processes “that ultimately destroy the skin.”

Urticaria and morbilliform eruptions, on the other hand, “are more simply that the immune system is recognizing COVID, and in doing so, is also recognizing some antigens in the skin and creating a hypersensitive response to the skin” and has “nothing to do with the SARS-CoV-2 virus actually being in that location,” she said.

It is important to differentiate between patients who have skin manifestations attributed to COVID-19 and those with manifestations independent of COVID-19, which is difficult, Dr. Femia noted. A patient with COVID-19 and a cutaneous manifestation may be having a reaction to a medication. “It’s important to have a critical eye and to remember that, when we see these manifestations, we should always be investigating whether there was an alternative cause so that we can better learn what exactly we should be attributing to this infection,” she said

Adam Friedman, MD, professor and interim chair of dermatology at George Washington University, Washington, said the authors of the review had presented interesting work, but made some “assumptions that need to be proven.” Dr. Friedman also was not involved in the research, but agreed in an interview with the assessment that it is unlikely SARS-CoV-2 would penetrate the skin. While some viruses – such as the poxvirus that causes molluscum contagiosum and the herpes simplex virus – invade keratinocytes specifically, there is a particular clinical phenotype that results that is associated with changes in the epidermis. However, “the skin manifestations of COVID-19 do not fit with direct skin invasion, [but] rather the immune response to systemic disease,” he said.

“[I]n terms of systemic invasion through the skin, it is possible, but this study certainly doesn’t show that. The presence/expression of ACE2 in the epidermis doesn’t translate to route of infection,” Dr. Friedman said..

The study received financial support from Shandong First Medical University, the Innovation Project of Shandong Academy of Medical Sciences and the Shandong Province Taishan Scholar Project. The authors report no relevant financial disclosures. Dr. Femia and Dr. Friedman had no relevant financial disclosures.

SOURCE: Zhao Q et al. J Eur Acad Dermatol Venereol. 2020 Jun 28. doi: 10.1111/jdv.16778.

When the pandemic was just emerging from its infancy and we were just beginning to think about social distancing, I was sitting around enjoying an adult beverage and some gluten free (not my choice) snacks with some friends. A retired nurse who had just celebrated her 80th birthday said, “I can’t wait until they’ve developed a vaccine.” A former electrical engineer sitting just short of 2 meters to her left responded, “Don’t save me a place near the front of the line for something that is being developed in a program called Warp Speed.”

Micah Young/istockphoto.com

How do you feel about the potential SARS-CoV-2 vaccine? Are you going to roll up your sleeve as soon as the vaccine becomes available in your community? What are you going to suggest to your patients, your children? I suspect many of you will answer, “It depends.” What factors will you be considering when you try to decide between what is likely to be several competing SARS-CoV-2 vaccines?

Will it make any difference to you which biochemical-immune-bending strategy is being used to make the vaccine? All of them will probably be the result of a clever sounding but novel technique, all of them with a track record that is measured in months and not years. Will you be swayed by how large the trials were? Or how long the follow-up lasted? How effective must the vaccine be to convince you that it is worth receiving or recommending? Do you have the tools and experience to make a decision like that? I know I don’t. And should you and I even be put in a position to make that decision?

In the past, you and I may have relied on the Centers for Disease Control and Prevention for advice. But given the somewhat murky and stormy relationship between the CDC and the president, the vaccine recommendation may be issued by the White House and not the CDC.

For those of us who were practicing medicine during the Swine Flu fiasco of 1976, the pace and the politics surrounding the development of a SARS-CoV-2 vaccine has a discomforting déjà vu quality about it. The fact that like this year 1976 was an election year that infused the development process with a sense of urgency above and beyond any of the concerns about the pandemic that never happened. Although causality was never proven, there was a surge in Guillain-Barré syndrome cases that had been linked temporally to the vaccine.

Of course, our pandemic is real, and it would be imprudent to wait a year or more to watch for long-term vaccine sequelae. However, I am more than a little concerned that fast tracking the development process may result in unfortunate consequences in the short term that could have been avoided with a more measured approach to trialing the vaccines.

The sad reality is that as a nation we tend to be impatient. We are drawn to quick fixes that come in a vial or a capsule. We are learning that simple measures like mask wearing and social distancing can make a difference in slowing the spread of the virus. It would be tragic to rush a vaccine into production that at best turns out to simply be an expensive alternative to the measures that we know work or at worst injures more of us than it saves.
 

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at [email protected].

When the pandemic was just emerging from its infancy and we were just beginning to think about social distancing, I was sitting around enjoying an adult beverage and some gluten free (not my choice) snacks with some friends. A retired nurse who had just celebrated her 80th birthday said, “I can’t wait until they’ve developed a vaccine.” A former electrical engineer sitting just short of 2 meters to her left responded, “Don’t save me a place near the front of the line for something that is being developed in a program called Warp Speed.”

Micah Young/istockphoto.com

How do you feel about the potential SARS-CoV-2 vaccine? Are you going to roll up your sleeve as soon as the vaccine becomes available in your community? What are you going to suggest to your patients, your children? I suspect many of you will answer, “It depends.” What factors will you be considering when you try to decide between what is likely to be several competing SARS-CoV-2 vaccines?

Will it make any difference to you which biochemical-immune-bending strategy is being used to make the vaccine? All of them will probably be the result of a clever sounding but novel technique, all of them with a track record that is measured in months and not years. Will you be swayed by how large the trials were? Or how long the follow-up lasted? How effective must the vaccine be to convince you that it is worth receiving or recommending? Do you have the tools and experience to make a decision like that? I know I don’t. And should you and I even be put in a position to make that decision?

In the past, you and I may have relied on the Centers for Disease Control and Prevention for advice. But given the somewhat murky and stormy relationship between the CDC and the president, the vaccine recommendation may be issued by the White House and not the CDC.

For those of us who were practicing medicine during the Swine Flu fiasco of 1976, the pace and the politics surrounding the development of a SARS-CoV-2 vaccine has a discomforting déjà vu quality about it. The fact that like this year 1976 was an election year that infused the development process with a sense of urgency above and beyond any of the concerns about the pandemic that never happened. Although causality was never proven, there was a surge in Guillain-Barré syndrome cases that had been linked temporally to the vaccine.

Of course, our pandemic is real, and it would be imprudent to wait a year or more to watch for long-term vaccine sequelae. However, I am more than a little concerned that fast tracking the development process may result in unfortunate consequences in the short term that could have been avoided with a more measured approach to trialing the vaccines.

The sad reality is that as a nation we tend to be impatient. We are drawn to quick fixes that come in a vial or a capsule. We are learning that simple measures like mask wearing and social distancing can make a difference in slowing the spread of the virus. It would be tragic to rush a vaccine into production that at best turns out to simply be an expensive alternative to the measures that we know work or at worst injures more of us than it saves.
 

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at [email protected].

When the pandemic was just emerging from its infancy and we were just beginning to think about social distancing, I was sitting around enjoying an adult beverage and some gluten free (not my choice) snacks with some friends. A retired nurse who had just celebrated her 80th birthday said, “I can’t wait until they’ve developed a vaccine.” A former electrical engineer sitting just short of 2 meters to her left responded, “Don’t save me a place near the front of the line for something that is being developed in a program called Warp Speed.”

Micah Young/istockphoto.com

How do you feel about the potential SARS-CoV-2 vaccine? Are you going to roll up your sleeve as soon as the vaccine becomes available in your community? What are you going to suggest to your patients, your children? I suspect many of you will answer, “It depends.” What factors will you be considering when you try to decide between what is likely to be several competing SARS-CoV-2 vaccines?

Will it make any difference to you which biochemical-immune-bending strategy is being used to make the vaccine? All of them will probably be the result of a clever sounding but novel technique, all of them with a track record that is measured in months and not years. Will you be swayed by how large the trials were? Or how long the follow-up lasted? How effective must the vaccine be to convince you that it is worth receiving or recommending? Do you have the tools and experience to make a decision like that? I know I don’t. And should you and I even be put in a position to make that decision?

In the past, you and I may have relied on the Centers for Disease Control and Prevention for advice. But given the somewhat murky and stormy relationship between the CDC and the president, the vaccine recommendation may be issued by the White House and not the CDC.

For those of us who were practicing medicine during the Swine Flu fiasco of 1976, the pace and the politics surrounding the development of a SARS-CoV-2 vaccine has a discomforting déjà vu quality about it. The fact that like this year 1976 was an election year that infused the development process with a sense of urgency above and beyond any of the concerns about the pandemic that never happened. Although causality was never proven, there was a surge in Guillain-Barré syndrome cases that had been linked temporally to the vaccine.

Of course, our pandemic is real, and it would be imprudent to wait a year or more to watch for long-term vaccine sequelae. However, I am more than a little concerned that fast tracking the development process may result in unfortunate consequences in the short term that could have been avoided with a more measured approach to trialing the vaccines.

The sad reality is that as a nation we tend to be impatient. We are drawn to quick fixes that come in a vial or a capsule. We are learning that simple measures like mask wearing and social distancing can make a difference in slowing the spread of the virus. It would be tragic to rush a vaccine into production that at best turns out to simply be an expensive alternative to the measures that we know work or at worst injures more of us than it saves.
 

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at [email protected].

It turns out that a pandemic, at least this COVID-19 version, can be a challenge for folks like me who are seldom at a loss for words. The pandemic has so overwhelmed every corner of our lives that it is hard to think of another topic on which to pontificate and still not tromp on someone’s political toes. One can always write about the pandemic itself, and I’ve tried that, but as the curtain is gradually being pulled back on this crafty little germ one runs the risk of making an observation today that will be disproved in a week or 2. However, I can’t suppress my urge to write, and so I have decided to share a few brief random observations. Of course they are related to the pandemic. And of course I realize that there is a better than fifty percent chance that they will be proved wrong by the time you read my next Letters from Maine.

Under the radar

Phynart Studio/Getty Images

Two of the many mysteries about SARS-CoV-2 involve young children who as a group appear to be less easily infected than adults and even when infected seem to be less likely to spread the disease to other people, particularly adults. One explanation posited by some researchers in France is that young children are less likely to have symptoms such as cough and are less powerful speakers and so might be less likely to spew out a significant number of infected aerosolized droplets (“How to Reopen Schools: What Science and Other Countries Teach Us.” By Pam Belluck, Apoorva Mandavill, and Benedict Carey. New York Times, July 11, 2020). While there are probably several factors to explain this observation, one may be that young children are short, seldom taller than an adult waistline. I suspect the majority of aerosols they emit fall and inactivate harmlessly to the floor several feet below an adult’s nose and mouth. Regardless of the explanation, it appears to be good news for the opening of schools, at least for the early grades.

Forget the deep cleaning

There has been a glut of news stories about reopening schools, and many of these stories are accompanied by images of school custodians with buckets, mops, spray bottles, and sponges scouring desks and walls. The most recent image in our local newspaper was of someone scrubbing the underside of a desk. I know it’s taking the World Health Organization an unconscionable period of time to acknowledge that SARS-CoV-2 is airborne, but the rest of us should have gotten the message long ago and been directing our attention to air handling and ventilation. The urge to scrub and deep clean is a hard habit to break, but this nasty bug is not like influenza or a flesh eating bacteria in which deep cleaning might help. A better image to attach to a story on school reopening would be one of a custodian with a screwdriver struggling to pry open a classroom window that had been painted shut a decade ago.

Managing the inevitable

Middlebury College in Vermont and Bowdoin College here in Brunswick, Maine, are similar in many respects because they are small and situated in relatively isolated small New England towns with good track records for pandemic management. Middlebury has elected to invite all its 2,750 students back to campus, whereas Bowdoin has decided to allow only incoming first years and transfer students (for a total of about 600) to return. Both schools will institute similar testing and social distancing protocols and restrict students from access to their respective towns (“A Tale of 2 Colleges.” By Bill Burger. Inside Higher Ed, June 29,2020). It will be an interesting experiment. I’m voting for Middlebury and not because my son and daughter-in-law are alums, but because I think Middlebury seems to have acknowledged that no matter how diligent one is in creating a SARS-CoV-2–free environment at the outset, these are college kids and there will be some cases on both campuses. It is on how those inevitable realities are managed and contained that an institution should be judged.

Patience

Unfortunately, the pandemic has exposed some of our weaknesses as a nation. We always have been a restless and impatient population eager to get moving and it has driven us to greatness. Hopefully, patience will be a lesson that we will learn, along with many others.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at [email protected].

It turns out that a pandemic, at least this COVID-19 version, can be a challenge for folks like me who are seldom at a loss for words. The pandemic has so overwhelmed every corner of our lives that it is hard to think of another topic on which to pontificate and still not tromp on someone’s political toes. One can always write about the pandemic itself, and I’ve tried that, but as the curtain is gradually being pulled back on this crafty little germ one runs the risk of making an observation today that will be disproved in a week or 2. However, I can’t suppress my urge to write, and so I have decided to share a few brief random observations. Of course they are related to the pandemic. And of course I realize that there is a better than fifty percent chance that they will be proved wrong by the time you read my next Letters from Maine.

Under the radar

Phynart Studio/Getty Images

Two of the many mysteries about SARS-CoV-2 involve young children who as a group appear to be less easily infected than adults and even when infected seem to be less likely to spread the disease to other people, particularly adults. One explanation posited by some researchers in France is that young children are less likely to have symptoms such as cough and are less powerful speakers and so might be less likely to spew out a significant number of infected aerosolized droplets (“How to Reopen Schools: What Science and Other Countries Teach Us.” By Pam Belluck, Apoorva Mandavill, and Benedict Carey. New York Times, July 11, 2020). While there are probably several factors to explain this observation, one may be that young children are short, seldom taller than an adult waistline. I suspect the majority of aerosols they emit fall and inactivate harmlessly to the floor several feet below an adult’s nose and mouth. Regardless of the explanation, it appears to be good news for the opening of schools, at least for the early grades.

Forget the deep cleaning

There has been a glut of news stories about reopening schools, and many of these stories are accompanied by images of school custodians with buckets, mops, spray bottles, and sponges scouring desks and walls. The most recent image in our local newspaper was of someone scrubbing the underside of a desk. I know it’s taking the World Health Organization an unconscionable period of time to acknowledge that SARS-CoV-2 is airborne, but the rest of us should have gotten the message long ago and been directing our attention to air handling and ventilation. The urge to scrub and deep clean is a hard habit to break, but this nasty bug is not like influenza or a flesh eating bacteria in which deep cleaning might help. A better image to attach to a story on school reopening would be one of a custodian with a screwdriver struggling to pry open a classroom window that had been painted shut a decade ago.

Managing the inevitable

Middlebury College in Vermont and Bowdoin College here in Brunswick, Maine, are similar in many respects because they are small and situated in relatively isolated small New England towns with good track records for pandemic management. Middlebury has elected to invite all its 2,750 students back to campus, whereas Bowdoin has decided to allow only incoming first years and transfer students (for a total of about 600) to return. Both schools will institute similar testing and social distancing protocols and restrict students from access to their respective towns (“A Tale of 2 Colleges.” By Bill Burger. Inside Higher Ed, June 29,2020). It will be an interesting experiment. I’m voting for Middlebury and not because my son and daughter-in-law are alums, but because I think Middlebury seems to have acknowledged that no matter how diligent one is in creating a SARS-CoV-2–free environment at the outset, these are college kids and there will be some cases on both campuses. It is on how those inevitable realities are managed and contained that an institution should be judged.

Patience

Unfortunately, the pandemic has exposed some of our weaknesses as a nation. We always have been a restless and impatient population eager to get moving and it has driven us to greatness. Hopefully, patience will be a lesson that we will learn, along with many others.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at [email protected].

It turns out that a pandemic, at least this COVID-19 version, can be a challenge for folks like me who are seldom at a loss for words. The pandemic has so overwhelmed every corner of our lives that it is hard to think of another topic on which to pontificate and still not tromp on someone’s political toes. One can always write about the pandemic itself, and I’ve tried that, but as the curtain is gradually being pulled back on this crafty little germ one runs the risk of making an observation today that will be disproved in a week or 2. However, I can’t suppress my urge to write, and so I have decided to share a few brief random observations. Of course they are related to the pandemic. And of course I realize that there is a better than fifty percent chance that they will be proved wrong by the time you read my next Letters from Maine.

Under the radar

Phynart Studio/Getty Images

Two of the many mysteries about SARS-CoV-2 involve young children who as a group appear to be less easily infected than adults and even when infected seem to be less likely to spread the disease to other people, particularly adults. One explanation posited by some researchers in France is that young children are less likely to have symptoms such as cough and are less powerful speakers and so might be less likely to spew out a significant number of infected aerosolized droplets (“How to Reopen Schools: What Science and Other Countries Teach Us.” By Pam Belluck, Apoorva Mandavill, and Benedict Carey. New York Times, July 11, 2020). While there are probably several factors to explain this observation, one may be that young children are short, seldom taller than an adult waistline. I suspect the majority of aerosols they emit fall and inactivate harmlessly to the floor several feet below an adult’s nose and mouth. Regardless of the explanation, it appears to be good news for the opening of schools, at least for the early grades.

Forget the deep cleaning

There has been a glut of news stories about reopening schools, and many of these stories are accompanied by images of school custodians with buckets, mops, spray bottles, and sponges scouring desks and walls. The most recent image in our local newspaper was of someone scrubbing the underside of a desk. I know it’s taking the World Health Organization an unconscionable period of time to acknowledge that SARS-CoV-2 is airborne, but the rest of us should have gotten the message long ago and been directing our attention to air handling and ventilation. The urge to scrub and deep clean is a hard habit to break, but this nasty bug is not like influenza or a flesh eating bacteria in which deep cleaning might help. A better image to attach to a story on school reopening would be one of a custodian with a screwdriver struggling to pry open a classroom window that had been painted shut a decade ago.

Managing the inevitable

Middlebury College in Vermont and Bowdoin College here in Brunswick, Maine, are similar in many respects because they are small and situated in relatively isolated small New England towns with good track records for pandemic management. Middlebury has elected to invite all its 2,750 students back to campus, whereas Bowdoin has decided to allow only incoming first years and transfer students (for a total of about 600) to return. Both schools will institute similar testing and social distancing protocols and restrict students from access to their respective towns (“A Tale of 2 Colleges.” By Bill Burger. Inside Higher Ed, June 29,2020). It will be an interesting experiment. I’m voting for Middlebury and not because my son and daughter-in-law are alums, but because I think Middlebury seems to have acknowledged that no matter how diligent one is in creating a SARS-CoV-2–free environment at the outset, these are college kids and there will be some cases on both campuses. It is on how those inevitable realities are managed and contained that an institution should be judged.

Patience

Unfortunately, the pandemic has exposed some of our weaknesses as a nation. We always have been a restless and impatient population eager to get moving and it has driven us to greatness. Hopefully, patience will be a lesson that we will learn, along with many others.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at [email protected].

Hospitalized cancer patients have a high risk of nosocomial COVID-19 that is associated with increased mortality, so these patients should be treated in COVID-free zones, according to researchers.

In an observational study of patients with COVID-19 and cancer, 19% of patients had COVID-19 acquired during a non-COVID-related hospital stay, and 81% had community-acquired COVID-19.

At a median follow-up of 23 days, the overall mortality rate was 28%. However, the all-cause mortality rate in patients with nosocomial COVID-19 was more than double that of patients with community-acquired COVID-19, at 47% and 23%, respectively.

Arielle Elkrief, MD, of the University of Montreal, reported these results during the AACR virtual meeting: COVID-19 and Cancer.

“This is the first report that describes a high rate of hospital-acquired COVID-19 in patients with cancer, at a rate of 19%,” Dr. Elkrief said. “This was associated with high mortality in both univariate and multivariate analyses.”

The study included 250 adults and 3 children with COVID-19 and cancer who were identified between March 3 and May 23, 2020. They ranged in age from 4 to 95 years, but the median age was 73 years.

All patients had either laboratory-confirmed (95%) or presumed COVID-19 (5%) and invasive cancer. The most common cancer types were similar to those seen in the general population. Lung and breast cancer were the most common, followed by lymphoma, prostate cancer, and colorectal cancer. Most patients were on active anticancer therapy, most often chemotherapy.

Most patients (n = 236) were residents of Quebec, but 17 patients were residents of British Columbia.

“It is important to note that Quebec was one of the most heavily affected areas in North America at the time of the study,” Dr. Elkrief said.
 

Outcomes by group

There were 206 patients (81%) who had community-acquired COVID-19 and 47 (19%) who had nosocomial COVID-19. The two groups were similar with respect to sex, performance status, and cancer stage. A small trend toward more patients on active therapy was seen in the nosocomial group, but the difference did not reach statistical significance.

The median overall survival was 27 days in the nosocomial group and 71 days in the community-acquired group (hazard ratio, 2.2; P = .002).

A multivariate analysis showed that nosocomial infection was “strongly and independently associated with death,” Dr. Elkrief said. “Other risk factors for poor prognosis included age, poor [performance] status, and advanced stage of cancer.”

There were no significant differences between the hospital-acquired and community-acquired groups for other outcomes, including oxygen requirements (43% and 47%, respectively), ICU admission (13% and 11%), need for mechanical ventilation (6% and 5%), or length of stay (median, 9.5 days and 8.5 days).

The low rate of ICU admission, considering the mortality rate of 28%, “could reflect that patients with cancer are less likely to be admitted to the ICU,” Dr. Elkrief noted.
 

Applying the findings to practice

The findings reinforce the importance of adherence to stringent infection control guidelines to protect vulnerable patients, such as those with cancer, Dr. Elkrief said.

In ambulatory settings, this means decreasing in-person visits through increased use of teleconsultations, and for those who need to be seen in person, screening for symptoms or use of polymerase chain reaction testing should be used when resources are available, she said.

“Similar principles apply to chemotherapy treatment units,” Dr. Elkrief said. She added that staff must avoid cross-contamination between COVID and COVID-free zones, and that “dedicated personnel and equipment should be maintained and separate between these two zones.

“Adequate protective personal equipment and strict hand hygiene protocols are also of utmost importance,” Dr. Elkrief said. “The threat of COVID-19 is not behind us, and so we continue to enforce these strategies to protect our patients.”

Session moderator Gypsyamber D’Souza, PhD, an infectious disease epidemiologist at Johns Hopkins University in Baltimore, raised the question of whether the high nosocomial infection and death rate in this study was related to patients having more severe disease because of underlying comorbidities.

Dr. Elkrief explained that the overall mortality rate was indeed higher than the 13% reported in other studies, and it may reflect an overrepresentation of hospitalized or more severely ill patients in the cohort.

However, the investigators made every effort to include all patients with both cancer and COVID-19 by using systematic screening of inpatient and outpatients lists and registries.

Further, the multivariate analysis included both inpatients and outpatients and adjusted for known negative prognostic factors for COVID-19 outcomes. These included increasing age, poor performance status, and different comorbidities.

The finding that nosocomial infection was an independent predictor of death “pushed us to look at nosocomial infection as a new independent risk factor,” Dr. Elkrief said.

Dr. Elkrief reported grant support from AstraZeneca. Dr. D’Souza did not report any disclosures.

[email protected]

SOURCE: Elkrief A et al. AACR: COVID and Cancer, Abstract S12-01.

Hospitalized cancer patients have a high risk of nosocomial COVID-19 that is associated with increased mortality, so these patients should be treated in COVID-free zones, according to researchers.

In an observational study of patients with COVID-19 and cancer, 19% of patients had COVID-19 acquired during a non-COVID-related hospital stay, and 81% had community-acquired COVID-19.

At a median follow-up of 23 days, the overall mortality rate was 28%. However, the all-cause mortality rate in patients with nosocomial COVID-19 was more than double that of patients with community-acquired COVID-19, at 47% and 23%, respectively.

Arielle Elkrief, MD, of the University of Montreal, reported these results during the AACR virtual meeting: COVID-19 and Cancer.

“This is the first report that describes a high rate of hospital-acquired COVID-19 in patients with cancer, at a rate of 19%,” Dr. Elkrief said. “This was associated with high mortality in both univariate and multivariate analyses.”

The study included 250 adults and 3 children with COVID-19 and cancer who were identified between March 3 and May 23, 2020. They ranged in age from 4 to 95 years, but the median age was 73 years.

All patients had either laboratory-confirmed (95%) or presumed COVID-19 (5%) and invasive cancer. The most common cancer types were similar to those seen in the general population. Lung and breast cancer were the most common, followed by lymphoma, prostate cancer, and colorectal cancer. Most patients were on active anticancer therapy, most often chemotherapy.

Most patients (n = 236) were residents of Quebec, but 17 patients were residents of British Columbia.

“It is important to note that Quebec was one of the most heavily affected areas in North America at the time of the study,” Dr. Elkrief said.
 

Outcomes by group

There were 206 patients (81%) who had community-acquired COVID-19 and 47 (19%) who had nosocomial COVID-19. The two groups were similar with respect to sex, performance status, and cancer stage. A small trend toward more patients on active therapy was seen in the nosocomial group, but the difference did not reach statistical significance.

The median overall survival was 27 days in the nosocomial group and 71 days in the community-acquired group (hazard ratio, 2.2; P = .002).

A multivariate analysis showed that nosocomial infection was “strongly and independently associated with death,” Dr. Elkrief said. “Other risk factors for poor prognosis included age, poor [performance] status, and advanced stage of cancer.”

There were no significant differences between the hospital-acquired and community-acquired groups for other outcomes, including oxygen requirements (43% and 47%, respectively), ICU admission (13% and 11%), need for mechanical ventilation (6% and 5%), or length of stay (median, 9.5 days and 8.5 days).

The low rate of ICU admission, considering the mortality rate of 28%, “could reflect that patients with cancer are less likely to be admitted to the ICU,” Dr. Elkrief noted.
 

Applying the findings to practice

The findings reinforce the importance of adherence to stringent infection control guidelines to protect vulnerable patients, such as those with cancer, Dr. Elkrief said.

In ambulatory settings, this means decreasing in-person visits through increased use of teleconsultations, and for those who need to be seen in person, screening for symptoms or use of polymerase chain reaction testing should be used when resources are available, she said.

“Similar principles apply to chemotherapy treatment units,” Dr. Elkrief said. She added that staff must avoid cross-contamination between COVID and COVID-free zones, and that “dedicated personnel and equipment should be maintained and separate between these two zones.

“Adequate protective personal equipment and strict hand hygiene protocols are also of utmost importance,” Dr. Elkrief said. “The threat of COVID-19 is not behind us, and so we continue to enforce these strategies to protect our patients.”

Session moderator Gypsyamber D’Souza, PhD, an infectious disease epidemiologist at Johns Hopkins University in Baltimore, raised the question of whether the high nosocomial infection and death rate in this study was related to patients having more severe disease because of underlying comorbidities.

Dr. Elkrief explained that the overall mortality rate was indeed higher than the 13% reported in other studies, and it may reflect an overrepresentation of hospitalized or more severely ill patients in the cohort.

However, the investigators made every effort to include all patients with both cancer and COVID-19 by using systematic screening of inpatient and outpatients lists and registries.

Further, the multivariate analysis included both inpatients and outpatients and adjusted for known negative prognostic factors for COVID-19 outcomes. These included increasing age, poor performance status, and different comorbidities.

The finding that nosocomial infection was an independent predictor of death “pushed us to look at nosocomial infection as a new independent risk factor,” Dr. Elkrief said.

Dr. Elkrief reported grant support from AstraZeneca. Dr. D’Souza did not report any disclosures.

[email protected]

SOURCE: Elkrief A et al. AACR: COVID and Cancer, Abstract S12-01.

Hospitalized cancer patients have a high risk of nosocomial COVID-19 that is associated with increased mortality, so these patients should be treated in COVID-free zones, according to researchers.

In an observational study of patients with COVID-19 and cancer, 19% of patients had COVID-19 acquired during a non-COVID-related hospital stay, and 81% had community-acquired COVID-19.

At a median follow-up of 23 days, the overall mortality rate was 28%. However, the all-cause mortality rate in patients with nosocomial COVID-19 was more than double that of patients with community-acquired COVID-19, at 47% and 23%, respectively.

Arielle Elkrief, MD, of the University of Montreal, reported these results during the AACR virtual meeting: COVID-19 and Cancer.

“This is the first report that describes a high rate of hospital-acquired COVID-19 in patients with cancer, at a rate of 19%,” Dr. Elkrief said. “This was associated with high mortality in both univariate and multivariate analyses.”

The study included 250 adults and 3 children with COVID-19 and cancer who were identified between March 3 and May 23, 2020. They ranged in age from 4 to 95 years, but the median age was 73 years.

All patients had either laboratory-confirmed (95%) or presumed COVID-19 (5%) and invasive cancer. The most common cancer types were similar to those seen in the general population. Lung and breast cancer were the most common, followed by lymphoma, prostate cancer, and colorectal cancer. Most patients were on active anticancer therapy, most often chemotherapy.

Most patients (n = 236) were residents of Quebec, but 17 patients were residents of British Columbia.

“It is important to note that Quebec was one of the most heavily affected areas in North America at the time of the study,” Dr. Elkrief said.
 

Outcomes by group

There were 206 patients (81%) who had community-acquired COVID-19 and 47 (19%) who had nosocomial COVID-19. The two groups were similar with respect to sex, performance status, and cancer stage. A small trend toward more patients on active therapy was seen in the nosocomial group, but the difference did not reach statistical significance.

The median overall survival was 27 days in the nosocomial group and 71 days in the community-acquired group (hazard ratio, 2.2; P = .002).

A multivariate analysis showed that nosocomial infection was “strongly and independently associated with death,” Dr. Elkrief said. “Other risk factors for poor prognosis included age, poor [performance] status, and advanced stage of cancer.”

There were no significant differences between the hospital-acquired and community-acquired groups for other outcomes, including oxygen requirements (43% and 47%, respectively), ICU admission (13% and 11%), need for mechanical ventilation (6% and 5%), or length of stay (median, 9.5 days and 8.5 days).

The low rate of ICU admission, considering the mortality rate of 28%, “could reflect that patients with cancer are less likely to be admitted to the ICU,” Dr. Elkrief noted.
 

Applying the findings to practice

The findings reinforce the importance of adherence to stringent infection control guidelines to protect vulnerable patients, such as those with cancer, Dr. Elkrief said.

In ambulatory settings, this means decreasing in-person visits through increased use of teleconsultations, and for those who need to be seen in person, screening for symptoms or use of polymerase chain reaction testing should be used when resources are available, she said.

“Similar principles apply to chemotherapy treatment units,” Dr. Elkrief said. She added that staff must avoid cross-contamination between COVID and COVID-free zones, and that “dedicated personnel and equipment should be maintained and separate between these two zones.

“Adequate protective personal equipment and strict hand hygiene protocols are also of utmost importance,” Dr. Elkrief said. “The threat of COVID-19 is not behind us, and so we continue to enforce these strategies to protect our patients.”

Session moderator Gypsyamber D’Souza, PhD, an infectious disease epidemiologist at Johns Hopkins University in Baltimore, raised the question of whether the high nosocomial infection and death rate in this study was related to patients having more severe disease because of underlying comorbidities.

Dr. Elkrief explained that the overall mortality rate was indeed higher than the 13% reported in other studies, and it may reflect an overrepresentation of hospitalized or more severely ill patients in the cohort.

However, the investigators made every effort to include all patients with both cancer and COVID-19 by using systematic screening of inpatient and outpatients lists and registries.

Further, the multivariate analysis included both inpatients and outpatients and adjusted for known negative prognostic factors for COVID-19 outcomes. These included increasing age, poor performance status, and different comorbidities.

The finding that nosocomial infection was an independent predictor of death “pushed us to look at nosocomial infection as a new independent risk factor,” Dr. Elkrief said.

Dr. Elkrief reported grant support from AstraZeneca. Dr. D’Souza did not report any disclosures.

[email protected]

SOURCE: Elkrief A et al. AACR: COVID and Cancer, Abstract S12-01.