Federal Practitioner

In December, at a major breast cancer conference, some attendees couldn’t find a seat and were told to leave an overcrowded session on immunotherapy for metastatic triple-negative breast cancer (TNBC). They refused, and pushed in to hear what was being said.

The crowd might have been surprised to learn that the main draw of the event, a successful new drug, was not all it might have been for women with the disease, being handicapped by a test that determines who is eligible for it.

“That room was overpacked ― there were five people deep against the wall. ... It was amazing,” said Janice Cowden of Bradenton, Florida. She attended the meeting, the San Antonio Breast Cancer Symposium, as a patient advocate.

Cowden lives with metastatic TNBC, which is known for poor prognoses, aggressiveness, and a lack of targeted treatment options. “Stage IV is a state of desperation. We just want something to work,” she said.

That’s why the conference room was packed – the session was focused on something that had been found to work – the immunotherapy atezolizumab (Tecentriq, Genentech/Roche).

Atezolizumab had recently been conditionally approved for first-line use in advanced TNBC, having been shown to significantly slow disease progression and, in some patients, to possibly improve survival. A pair of medical oncologists reviewed the clinical trial data during the session.

One important point from the trial data was that the benefit was greater in patients whose tumors had the biomarker PD-L1, and so the Food and Drug Administration approval of the drug specified that it should be used only in those patients.

The drug approval was accompanied by approval of a companion diagnostic test used to identify this PD-L1-positive subgroup of patients, the Ventana SP142 Assay (Roche Diagnostics).

At the meeting, pathologist David Rimm, MD, of Yale University, New Haven, Connecticut, discussed the biomarker PD-L1 and the test. Rimm had a subtle but unsettling message about the crucial test: that the SP142 diagnostic assay, when used by increasing numbers of pathologists, resulted in increasing rates of PD-L1 scores that were not concordant.

A related meeting poster, presented the next day with Rimm as senior author, was more explicit and concluded that “more than half of the pathologists in real-world situations may mis- assign” patient scores with SP142 (and another Roche assay) because of wide variability in readouts.

“They’ve made a test that is inadequate – it just doesn’t work. It’s like flipping a coin,” he told Medscape Medical News about Roche’s SP142 assay in everyday practice.

The general problem is not a new one – for some years there have been problems with the use of PD-L1 as a biomarker for immunotherapy and with assays for that biomarker, with many groups questioning both accuracy and reproducibility. But the problems with SP142 are “the most egregious,” said Rimm, who has served as a paid consultant to Roche Diagnostics in the past.

In clinical practice, Rimm’s overall message is that because of the difficulty of reading SP142 assay results, some TNBC patients who were PD-L1-positive would not get the drug, and some who were not positive would get the drug.

Patient advocate Cowden was not worried about overtreatment. She was concerned about patients who “might die without receiving a potentially life-extending treatment.”

In an essay in the Pathologist, Rimm echoed that sentiment about undertreatment (as well as overtreatment) with atezolizumab for breast cancer: “In all cases, the patients are the potential victims, but this appears to be completely under the radar of the hype surrounding this new drug.”
 

Roche Disputes Problems With Assay

Roche, manufacturer of both atezolizumab and the companion diagnostic test, disputes that there is a problem.

The FDA and multiple health authorities worldwide have approved atezolizumab and the companion diagnostic SP142 assay for use in TNBC, points out Eslie Dennis, MD, vice president of medical affairs at Roche Tissue Diagnostics.

“The role of a companion diagnostic assay is to discriminate between responders and non-responders for a specific therapeutic product in a specific indication, with a cut-off based on clinical outcomes,” she wrote in an email to Medscape Medical News.

Data from the pivotal IMpassion130 trial show that the assay was effective at that task. Among the 369 patients in the 902-patient trial whose tumors were ≥1% positive for PD-L1, those treated with atezolizumab (and nab-paclitaxel; n = 185) had a median progression-free survival (PFS) of 7.4 months, vs. 4.8 months among those treated with placebo (and nab-paclitaxel; n = 184) (P < .0001).

“Exploratory analysis showed no [PFS] benefit in PD-L1-negative patients as tested by the SP142 assay [in IMpassion130],” Dennis and three other physicians write in a reply to Rimm in a letter published in July 2019 in the Pathologist.

The same held true for overall survival in exploratory analysis – there was no benefit with atezolizumab among the PD-L1-negative patients, they write.

Notably, overall survival benefit for patients who were PD-L1 positive was about 10 months (at the first interim analysis; at the second analysis, the benefit dropped to 7 months and was not statistically significant).

But Rimm points out that the pivotal trial used only one pathologist in a central lab to determine PD-L1 status, who was undoubtedly an expert with the SP142 assay.

Further, Rimm observes that additional data submitted to the FDA to show that SP142 test results are reproducible outside of the pivotal trial setting were performed with only three pathologists and thus unsurprisingly yielded high rates of agreement – all above 90%.

The data from both of these circumstances are problematic, Rimm said, because in the real world, hundreds of pathologists will score the SP142 assay – all in the context of a busy day reading a variety of other tests for other diseases.

It’s one thing to get an FDA approval for an assay, and it’s another thing to be a reliable, well-functioning assay in the real world, he summarized.

Last year, Roberto Salgado, MD, PhD, a pathologist at the Université Libre de Bruxelles, Belgium, commented that “a positive phase III trial should not be taken as a guarantee that the assay used in the trial can be implemented in daily practice” in an opinion piece in the Pathologist.
 

SP142 Identifies the “Fewest Possible Patients”

The SP142 assay has been shown in multiple studies to have lower sensitivity for PD-L1 than other competing PD-L1 assays, said Rimm, citing examples such as a 2017 study and a 2018 study.

Angela DeMichele, MD, a medical oncologist at the University of Pennsylvania in Philadelphia, agreed and explained what that meant in practical terms for women whose tumors are tested with SP142. “It means that the test is going to identify the fewest possible PD-L1-positive patients [relative to the other available assays],” she said. “It [the SP142 assay] is far from a perfect test for this situation,” added DeMichele, an expert on biomarkers in breast cancer clinical trials.

She said that biomarker tests, like many products of science, tend to become dated with the passage of time, as more is learned about the target and new assays are developed. “Unfortunately, you can’t change assays midstream,” said DeMichele. She has received a grant from Roche and Stand Up to Cancer to study atezolizumab and another drug in a clinical trial among patients with metastatic TNBC who have minimal residual disease.

DeMichele also said that “David Rimm is one of the most knowledgeable people in the world about this issue.”

But DeMichelle also points out the practical: “We’re stuck as clinicians” because regulatory bodies and insurance companies only pay for atezolizumab when the SP142 assay indicates PD-L1 positivity. That’s not the case in Europe, where health authorities do not specify which PD-L1 assay is to be used with atezolizumab for breast cancer, pointed out Belgium’s Salgado last year.
 

Another Level of Complexity

At the immunotherapy session in San Antonio, Rimm discussed the results of a study of 68 TNBC archived cases in which specimens were stained with the SP142 assay at Yale and were distributed via electronic images to 19 pathologists at 14 institutions across the United States for PD-L1 scoring.

The study, coauthored by academics from Iowa, Texas A&M, UC San Diego, Mayo Clinic, Memorial Sloan Kettering, and others, used a novel method to determine the minimum number of evaluators needed to estimate “concordance” or agreement about a test result among large numbers of readers. The consensus/agreement was as high as 80% when eight or fewer pathologists’ scores were compared, but was as low as 40% when results from more than eight pathologists were included, said Rimm.

These are some of the data that led him to declare that using the assay is no better than flipping a coin.

Yes, PD-L1 testing is a challenge, and it has “introduced another level of complexity” for pathologists in reading assays, write experts Emina Torlakovic, MD, University of Saskatchewan, Canada, and Allen Gown, MD, PhenoPath Laboratories, Seattle, in response to Rimm last year.

But there is “poor” consensus among pathologists, they point out, “for many scoring systems that are still clinically applied (such as Gleason grading).” Consensus “improves with education and training,” the pair add. To that end, Roche has initiated a global training program for pathologists using the SP142 assay for TNBC. At San Antonio, Roche’s Dennis reported that among 432 pathologists from 58 countries, there was overall agreement of 98.2% in scoring assays.

Rimm commented that such high agreement would not be a surprise if testing took place soon after any such training program.

In an email to Medscape Medical News, Torlakovic encouraged pathologists who wish to practice their skill in interpreting assays, including SP142, to visit CBQAReadout.ca, a testing site. The site, which was founded by Torlakovic and may be one of a kind, offers CME credits and is sponsored by independent pathology organizations, such as CAP-ACP and the Saskatchewan Health Authority, as well as pharmaceutical companies, including Roche.

No Clue

Patient advocate Cowden believes the controversy about PD-L1 testing for atezolizumab is largely unknown among breast cancer patients. She learned about SP142 assay ambiguities in San Antonio, when the Florida Breast Cancer Foundation funded her trip to the meeting and the Alamo Breast Cancer Foundation asked her to write a report on Rimm’s presentation.

Cowden is a member of a Facebook group for stage IV TNBC, which has about 1500 members. She estimates that 75%-80% would be willing to try atezolizumab “no matter what,” meaning they don’t care about PD-L1 positivity being associated with efficacy.

The Facebook group members “know there is a test and if you are positive, there is an immunotherapy for their breast cancer,” said Cowden.

None know that women may be excluded from treatment because of shortcomings with the SP142 test. “They have no clue,” she said.

Rimm and DeMichele have financial ties to Roche and other companies. Dennis is an employee of Roche. Torlakovic has ties to multiple companies, including Roche, for whom she has acted as a paid consultant, grant recipient, and paid lecturer. Gown did not respond to a request for financial disclosures. Cowden reports no relevant financial relationships.

This article first appeared on Medscape.com.

In December, at a major breast cancer conference, some attendees couldn’t find a seat and were told to leave an overcrowded session on immunotherapy for metastatic triple-negative breast cancer (TNBC). They refused, and pushed in to hear what was being said.

The crowd might have been surprised to learn that the main draw of the event, a successful new drug, was not all it might have been for women with the disease, being handicapped by a test that determines who is eligible for it.

“That room was overpacked ― there were five people deep against the wall. ... It was amazing,” said Janice Cowden of Bradenton, Florida. She attended the meeting, the San Antonio Breast Cancer Symposium, as a patient advocate.

Cowden lives with metastatic TNBC, which is known for poor prognoses, aggressiveness, and a lack of targeted treatment options. “Stage IV is a state of desperation. We just want something to work,” she said.

That’s why the conference room was packed – the session was focused on something that had been found to work – the immunotherapy atezolizumab (Tecentriq, Genentech/Roche).

Atezolizumab had recently been conditionally approved for first-line use in advanced TNBC, having been shown to significantly slow disease progression and, in some patients, to possibly improve survival. A pair of medical oncologists reviewed the clinical trial data during the session.

One important point from the trial data was that the benefit was greater in patients whose tumors had the biomarker PD-L1, and so the Food and Drug Administration approval of the drug specified that it should be used only in those patients.

The drug approval was accompanied by approval of a companion diagnostic test used to identify this PD-L1-positive subgroup of patients, the Ventana SP142 Assay (Roche Diagnostics).

At the meeting, pathologist David Rimm, MD, of Yale University, New Haven, Connecticut, discussed the biomarker PD-L1 and the test. Rimm had a subtle but unsettling message about the crucial test: that the SP142 diagnostic assay, when used by increasing numbers of pathologists, resulted in increasing rates of PD-L1 scores that were not concordant.

A related meeting poster, presented the next day with Rimm as senior author, was more explicit and concluded that “more than half of the pathologists in real-world situations may mis- assign” patient scores with SP142 (and another Roche assay) because of wide variability in readouts.

“They’ve made a test that is inadequate – it just doesn’t work. It’s like flipping a coin,” he told Medscape Medical News about Roche’s SP142 assay in everyday practice.

The general problem is not a new one – for some years there have been problems with the use of PD-L1 as a biomarker for immunotherapy and with assays for that biomarker, with many groups questioning both accuracy and reproducibility. But the problems with SP142 are “the most egregious,” said Rimm, who has served as a paid consultant to Roche Diagnostics in the past.

In clinical practice, Rimm’s overall message is that because of the difficulty of reading SP142 assay results, some TNBC patients who were PD-L1-positive would not get the drug, and some who were not positive would get the drug.

Patient advocate Cowden was not worried about overtreatment. She was concerned about patients who “might die without receiving a potentially life-extending treatment.”

In an essay in the Pathologist, Rimm echoed that sentiment about undertreatment (as well as overtreatment) with atezolizumab for breast cancer: “In all cases, the patients are the potential victims, but this appears to be completely under the radar of the hype surrounding this new drug.”
 

Roche Disputes Problems With Assay

Roche, manufacturer of both atezolizumab and the companion diagnostic test, disputes that there is a problem.

The FDA and multiple health authorities worldwide have approved atezolizumab and the companion diagnostic SP142 assay for use in TNBC, points out Eslie Dennis, MD, vice president of medical affairs at Roche Tissue Diagnostics.

“The role of a companion diagnostic assay is to discriminate between responders and non-responders for a specific therapeutic product in a specific indication, with a cut-off based on clinical outcomes,” she wrote in an email to Medscape Medical News.

Data from the pivotal IMpassion130 trial show that the assay was effective at that task. Among the 369 patients in the 902-patient trial whose tumors were ≥1% positive for PD-L1, those treated with atezolizumab (and nab-paclitaxel; n = 185) had a median progression-free survival (PFS) of 7.4 months, vs. 4.8 months among those treated with placebo (and nab-paclitaxel; n = 184) (P < .0001).

“Exploratory analysis showed no [PFS] benefit in PD-L1-negative patients as tested by the SP142 assay [in IMpassion130],” Dennis and three other physicians write in a reply to Rimm in a letter published in July 2019 in the Pathologist.

The same held true for overall survival in exploratory analysis – there was no benefit with atezolizumab among the PD-L1-negative patients, they write.

Notably, overall survival benefit for patients who were PD-L1 positive was about 10 months (at the first interim analysis; at the second analysis, the benefit dropped to 7 months and was not statistically significant).

But Rimm points out that the pivotal trial used only one pathologist in a central lab to determine PD-L1 status, who was undoubtedly an expert with the SP142 assay.

Further, Rimm observes that additional data submitted to the FDA to show that SP142 test results are reproducible outside of the pivotal trial setting were performed with only three pathologists and thus unsurprisingly yielded high rates of agreement – all above 90%.

The data from both of these circumstances are problematic, Rimm said, because in the real world, hundreds of pathologists will score the SP142 assay – all in the context of a busy day reading a variety of other tests for other diseases.

It’s one thing to get an FDA approval for an assay, and it’s another thing to be a reliable, well-functioning assay in the real world, he summarized.

Last year, Roberto Salgado, MD, PhD, a pathologist at the Université Libre de Bruxelles, Belgium, commented that “a positive phase III trial should not be taken as a guarantee that the assay used in the trial can be implemented in daily practice” in an opinion piece in the Pathologist.
 

SP142 Identifies the “Fewest Possible Patients”

The SP142 assay has been shown in multiple studies to have lower sensitivity for PD-L1 than other competing PD-L1 assays, said Rimm, citing examples such as a 2017 study and a 2018 study.

Angela DeMichele, MD, a medical oncologist at the University of Pennsylvania in Philadelphia, agreed and explained what that meant in practical terms for women whose tumors are tested with SP142. “It means that the test is going to identify the fewest possible PD-L1-positive patients [relative to the other available assays],” she said. “It [the SP142 assay] is far from a perfect test for this situation,” added DeMichele, an expert on biomarkers in breast cancer clinical trials.

She said that biomarker tests, like many products of science, tend to become dated with the passage of time, as more is learned about the target and new assays are developed. “Unfortunately, you can’t change assays midstream,” said DeMichele. She has received a grant from Roche and Stand Up to Cancer to study atezolizumab and another drug in a clinical trial among patients with metastatic TNBC who have minimal residual disease.

DeMichele also said that “David Rimm is one of the most knowledgeable people in the world about this issue.”

But DeMichelle also points out the practical: “We’re stuck as clinicians” because regulatory bodies and insurance companies only pay for atezolizumab when the SP142 assay indicates PD-L1 positivity. That’s not the case in Europe, where health authorities do not specify which PD-L1 assay is to be used with atezolizumab for breast cancer, pointed out Belgium’s Salgado last year.
 

Another Level of Complexity

At the immunotherapy session in San Antonio, Rimm discussed the results of a study of 68 TNBC archived cases in which specimens were stained with the SP142 assay at Yale and were distributed via electronic images to 19 pathologists at 14 institutions across the United States for PD-L1 scoring.

The study, coauthored by academics from Iowa, Texas A&M, UC San Diego, Mayo Clinic, Memorial Sloan Kettering, and others, used a novel method to determine the minimum number of evaluators needed to estimate “concordance” or agreement about a test result among large numbers of readers. The consensus/agreement was as high as 80% when eight or fewer pathologists’ scores were compared, but was as low as 40% when results from more than eight pathologists were included, said Rimm.

These are some of the data that led him to declare that using the assay is no better than flipping a coin.

Yes, PD-L1 testing is a challenge, and it has “introduced another level of complexity” for pathologists in reading assays, write experts Emina Torlakovic, MD, University of Saskatchewan, Canada, and Allen Gown, MD, PhenoPath Laboratories, Seattle, in response to Rimm last year.

But there is “poor” consensus among pathologists, they point out, “for many scoring systems that are still clinically applied (such as Gleason grading).” Consensus “improves with education and training,” the pair add. To that end, Roche has initiated a global training program for pathologists using the SP142 assay for TNBC. At San Antonio, Roche’s Dennis reported that among 432 pathologists from 58 countries, there was overall agreement of 98.2% in scoring assays.

Rimm commented that such high agreement would not be a surprise if testing took place soon after any such training program.

In an email to Medscape Medical News, Torlakovic encouraged pathologists who wish to practice their skill in interpreting assays, including SP142, to visit CBQAReadout.ca, a testing site. The site, which was founded by Torlakovic and may be one of a kind, offers CME credits and is sponsored by independent pathology organizations, such as CAP-ACP and the Saskatchewan Health Authority, as well as pharmaceutical companies, including Roche.

No Clue

Patient advocate Cowden believes the controversy about PD-L1 testing for atezolizumab is largely unknown among breast cancer patients. She learned about SP142 assay ambiguities in San Antonio, when the Florida Breast Cancer Foundation funded her trip to the meeting and the Alamo Breast Cancer Foundation asked her to write a report on Rimm’s presentation.

Cowden is a member of a Facebook group for stage IV TNBC, which has about 1500 members. She estimates that 75%-80% would be willing to try atezolizumab “no matter what,” meaning they don’t care about PD-L1 positivity being associated with efficacy.

The Facebook group members “know there is a test and if you are positive, there is an immunotherapy for their breast cancer,” said Cowden.

None know that women may be excluded from treatment because of shortcomings with the SP142 test. “They have no clue,” she said.

Rimm and DeMichele have financial ties to Roche and other companies. Dennis is an employee of Roche. Torlakovic has ties to multiple companies, including Roche, for whom she has acted as a paid consultant, grant recipient, and paid lecturer. Gown did not respond to a request for financial disclosures. Cowden reports no relevant financial relationships.

This article first appeared on Medscape.com.

In December, at a major breast cancer conference, some attendees couldn’t find a seat and were told to leave an overcrowded session on immunotherapy for metastatic triple-negative breast cancer (TNBC). They refused, and pushed in to hear what was being said.

The crowd might have been surprised to learn that the main draw of the event, a successful new drug, was not all it might have been for women with the disease, being handicapped by a test that determines who is eligible for it.

“That room was overpacked ― there were five people deep against the wall. ... It was amazing,” said Janice Cowden of Bradenton, Florida. She attended the meeting, the San Antonio Breast Cancer Symposium, as a patient advocate.

Cowden lives with metastatic TNBC, which is known for poor prognoses, aggressiveness, and a lack of targeted treatment options. “Stage IV is a state of desperation. We just want something to work,” she said.

That’s why the conference room was packed – the session was focused on something that had been found to work – the immunotherapy atezolizumab (Tecentriq, Genentech/Roche).

Atezolizumab had recently been conditionally approved for first-line use in advanced TNBC, having been shown to significantly slow disease progression and, in some patients, to possibly improve survival. A pair of medical oncologists reviewed the clinical trial data during the session.

One important point from the trial data was that the benefit was greater in patients whose tumors had the biomarker PD-L1, and so the Food and Drug Administration approval of the drug specified that it should be used only in those patients.

The drug approval was accompanied by approval of a companion diagnostic test used to identify this PD-L1-positive subgroup of patients, the Ventana SP142 Assay (Roche Diagnostics).

At the meeting, pathologist David Rimm, MD, of Yale University, New Haven, Connecticut, discussed the biomarker PD-L1 and the test. Rimm had a subtle but unsettling message about the crucial test: that the SP142 diagnostic assay, when used by increasing numbers of pathologists, resulted in increasing rates of PD-L1 scores that were not concordant.

A related meeting poster, presented the next day with Rimm as senior author, was more explicit and concluded that “more than half of the pathologists in real-world situations may mis- assign” patient scores with SP142 (and another Roche assay) because of wide variability in readouts.

“They’ve made a test that is inadequate – it just doesn’t work. It’s like flipping a coin,” he told Medscape Medical News about Roche’s SP142 assay in everyday practice.

The general problem is not a new one – for some years there have been problems with the use of PD-L1 as a biomarker for immunotherapy and with assays for that biomarker, with many groups questioning both accuracy and reproducibility. But the problems with SP142 are “the most egregious,” said Rimm, who has served as a paid consultant to Roche Diagnostics in the past.

In clinical practice, Rimm’s overall message is that because of the difficulty of reading SP142 assay results, some TNBC patients who were PD-L1-positive would not get the drug, and some who were not positive would get the drug.

Patient advocate Cowden was not worried about overtreatment. She was concerned about patients who “might die without receiving a potentially life-extending treatment.”

In an essay in the Pathologist, Rimm echoed that sentiment about undertreatment (as well as overtreatment) with atezolizumab for breast cancer: “In all cases, the patients are the potential victims, but this appears to be completely under the radar of the hype surrounding this new drug.”
 

Roche Disputes Problems With Assay

Roche, manufacturer of both atezolizumab and the companion diagnostic test, disputes that there is a problem.

The FDA and multiple health authorities worldwide have approved atezolizumab and the companion diagnostic SP142 assay for use in TNBC, points out Eslie Dennis, MD, vice president of medical affairs at Roche Tissue Diagnostics.

“The role of a companion diagnostic assay is to discriminate between responders and non-responders for a specific therapeutic product in a specific indication, with a cut-off based on clinical outcomes,” she wrote in an email to Medscape Medical News.

Data from the pivotal IMpassion130 trial show that the assay was effective at that task. Among the 369 patients in the 902-patient trial whose tumors were ≥1% positive for PD-L1, those treated with atezolizumab (and nab-paclitaxel; n = 185) had a median progression-free survival (PFS) of 7.4 months, vs. 4.8 months among those treated with placebo (and nab-paclitaxel; n = 184) (P < .0001).

“Exploratory analysis showed no [PFS] benefit in PD-L1-negative patients as tested by the SP142 assay [in IMpassion130],” Dennis and three other physicians write in a reply to Rimm in a letter published in July 2019 in the Pathologist.

The same held true for overall survival in exploratory analysis – there was no benefit with atezolizumab among the PD-L1-negative patients, they write.

Notably, overall survival benefit for patients who were PD-L1 positive was about 10 months (at the first interim analysis; at the second analysis, the benefit dropped to 7 months and was not statistically significant).

But Rimm points out that the pivotal trial used only one pathologist in a central lab to determine PD-L1 status, who was undoubtedly an expert with the SP142 assay.

Further, Rimm observes that additional data submitted to the FDA to show that SP142 test results are reproducible outside of the pivotal trial setting were performed with only three pathologists and thus unsurprisingly yielded high rates of agreement – all above 90%.

The data from both of these circumstances are problematic, Rimm said, because in the real world, hundreds of pathologists will score the SP142 assay – all in the context of a busy day reading a variety of other tests for other diseases.

It’s one thing to get an FDA approval for an assay, and it’s another thing to be a reliable, well-functioning assay in the real world, he summarized.

Last year, Roberto Salgado, MD, PhD, a pathologist at the Université Libre de Bruxelles, Belgium, commented that “a positive phase III trial should not be taken as a guarantee that the assay used in the trial can be implemented in daily practice” in an opinion piece in the Pathologist.
 

SP142 Identifies the “Fewest Possible Patients”

The SP142 assay has been shown in multiple studies to have lower sensitivity for PD-L1 than other competing PD-L1 assays, said Rimm, citing examples such as a 2017 study and a 2018 study.

Angela DeMichele, MD, a medical oncologist at the University of Pennsylvania in Philadelphia, agreed and explained what that meant in practical terms for women whose tumors are tested with SP142. “It means that the test is going to identify the fewest possible PD-L1-positive patients [relative to the other available assays],” she said. “It [the SP142 assay] is far from a perfect test for this situation,” added DeMichele, an expert on biomarkers in breast cancer clinical trials.

She said that biomarker tests, like many products of science, tend to become dated with the passage of time, as more is learned about the target and new assays are developed. “Unfortunately, you can’t change assays midstream,” said DeMichele. She has received a grant from Roche and Stand Up to Cancer to study atezolizumab and another drug in a clinical trial among patients with metastatic TNBC who have minimal residual disease.

DeMichele also said that “David Rimm is one of the most knowledgeable people in the world about this issue.”

But DeMichelle also points out the practical: “We’re stuck as clinicians” because regulatory bodies and insurance companies only pay for atezolizumab when the SP142 assay indicates PD-L1 positivity. That’s not the case in Europe, where health authorities do not specify which PD-L1 assay is to be used with atezolizumab for breast cancer, pointed out Belgium’s Salgado last year.
 

Another Level of Complexity

At the immunotherapy session in San Antonio, Rimm discussed the results of a study of 68 TNBC archived cases in which specimens were stained with the SP142 assay at Yale and were distributed via electronic images to 19 pathologists at 14 institutions across the United States for PD-L1 scoring.

The study, coauthored by academics from Iowa, Texas A&M, UC San Diego, Mayo Clinic, Memorial Sloan Kettering, and others, used a novel method to determine the minimum number of evaluators needed to estimate “concordance” or agreement about a test result among large numbers of readers. The consensus/agreement was as high as 80% when eight or fewer pathologists’ scores were compared, but was as low as 40% when results from more than eight pathologists were included, said Rimm.

These are some of the data that led him to declare that using the assay is no better than flipping a coin.

Yes, PD-L1 testing is a challenge, and it has “introduced another level of complexity” for pathologists in reading assays, write experts Emina Torlakovic, MD, University of Saskatchewan, Canada, and Allen Gown, MD, PhenoPath Laboratories, Seattle, in response to Rimm last year.

But there is “poor” consensus among pathologists, they point out, “for many scoring systems that are still clinically applied (such as Gleason grading).” Consensus “improves with education and training,” the pair add. To that end, Roche has initiated a global training program for pathologists using the SP142 assay for TNBC. At San Antonio, Roche’s Dennis reported that among 432 pathologists from 58 countries, there was overall agreement of 98.2% in scoring assays.

Rimm commented that such high agreement would not be a surprise if testing took place soon after any such training program.

In an email to Medscape Medical News, Torlakovic encouraged pathologists who wish to practice their skill in interpreting assays, including SP142, to visit CBQAReadout.ca, a testing site. The site, which was founded by Torlakovic and may be one of a kind, offers CME credits and is sponsored by independent pathology organizations, such as CAP-ACP and the Saskatchewan Health Authority, as well as pharmaceutical companies, including Roche.

No Clue

Patient advocate Cowden believes the controversy about PD-L1 testing for atezolizumab is largely unknown among breast cancer patients. She learned about SP142 assay ambiguities in San Antonio, when the Florida Breast Cancer Foundation funded her trip to the meeting and the Alamo Breast Cancer Foundation asked her to write a report on Rimm’s presentation.

Cowden is a member of a Facebook group for stage IV TNBC, which has about 1500 members. She estimates that 75%-80% would be willing to try atezolizumab “no matter what,” meaning they don’t care about PD-L1 positivity being associated with efficacy.

The Facebook group members “know there is a test and if you are positive, there is an immunotherapy for their breast cancer,” said Cowden.

None know that women may be excluded from treatment because of shortcomings with the SP142 test. “They have no clue,” she said.

Rimm and DeMichele have financial ties to Roche and other companies. Dennis is an employee of Roche. Torlakovic has ties to multiple companies, including Roche, for whom she has acted as a paid consultant, grant recipient, and paid lecturer. Gown did not respond to a request for financial disclosures. Cowden reports no relevant financial relationships.

This article first appeared on Medscape.com.

The novel coronavirus, SARS-CoV-2, remains viable in aerosols for hours and on surfaces for days, according to a new study.

The data indicate that the stability of the new virus is similar to that of SARS-CoV-1, which caused the SARS epidemic, researchers report in an article published on the medRxivpreprint server. (The posted article has been submitted for journal publication but has not been peer reviewed.)

Transmission of SARS-CoV-2, which causes COVID-19, has quickly outstripped the pace of the 2003 SARS epidemic. “Superspread” of the earlier disease arose from infection during medical procedures, in which a single infected individual seeded many secondary cases. In contrast, the novel coronavirus appears to be spread more through human-to-human transmission in a variety of settings.

However, it’s not yet known the extent to which asymptomatic or presymptomatic individuals spread the new virus through daily routine.

To investigate how long SARS-CoV-2 remains infective in the environment, Neeltje van Doremalen, PhD, of the Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, in Hamilton, Montana, and colleagues conducted simulation experiments in which they compared the viability of SARS-CoV-2 with that of SARS-CoV-1 in aerosols and on surfaces.

Among patients infected with SARS-CoV-2, viral loads in the upper respiratory tract are high; as a consequence, respiratory secretion in the form of aerosols (<5 μm) or droplets (>5 mcm) is likely, the authors note.

van Doremalen and colleagues used nebulizers to generate aerosols. Samples of SARS-CoV-1 and SARS-CoV-2 were collecting at 0, 30, 60, 120, and 180 minutes on a gelatin filter. The researchers then tested the infectivity of the viruses on Vero cells grown in culture.

They found that SARS-CoV-2 was largely stable through the full 180-minute test, with only a slight decline at 3 hours. This time course is similar to that of SARS-CoV-1; both viruses have a median half-life in aerosols of 2.7 hours (range, 1.65 hr for SARS-CoV-1, vs 7.24 hr for SARS-CoV-2).

The researchers then tested the viruses on a variety of surfaces for up to 7 days, using humidity values and temperatures designed to mimic “a variety of household and hospital situations.” The volumes of viral exposures that the team used were consistent with amounts found in the human upper and lower respiratory tracts.

For example, they applied 50 mcL of virus-containing solution to a piece of cardboard and then swabbed the surface, at different times, with an additional 1 mcL of medium. Each surface assay was replicated three times.

The novel coronavirus was most stable on plastic and stainless steel, with some virus remaining viable up to 72 hours. However, by that time the viral load had fallen by about three orders of magnitude, indicating exponential decay. This profile was remarkably similar to that of SARS-CoV-1, according to the authors.

However, the two viruses differed in staying power on copper and cardboard. No viable SARS-CoV-2 was detectable on copper after 4 hours or on cardboard after 24 hours. In contrast, SARS-CoV-1 was not viable beyond 8 hours for either copper or cardboard.

“Taken together, our results indicate that aerosol and fomite transmission of HCoV-19 [SARS-CoV-2] are plausible, as the virus can remain viable in aerosols for multiple hours and on surfaces up to days,” the authors conclude.

Andrew Pekosz, PhD, codirector of the Center of Excellence in Influenza Research and Surveillance and director of the Center for Emerging Viruses and Infectious Diseases at the Johns Hopkins Center for Global Health, Baltimore, Maryland, applauds the real-world value of the experiments.

“The PCR [polymerase chain reaction] test used [in other studies] to detect SARS-CoV-2 just detects the virus genome. It doesn’t tell you if the virus was still infectious, or ‘viable.’ That’s why this study is interesting,” Pekosz said. “It focuses on infectious virus, which is the virus that has the potential to transmit and infect another person. What we don’t know yet is how much infectious (viable) virus is needed to initiate infection in another person.”

He suggests that further investigations evaluate other types of environmental surfaces, including lacquered wood that is made into desks and ceramic tiles found in bathrooms and kitchens.

One limitation of the study is that the data for experiments on cardboard were more variable than the data for other surfaces tested.

The investigators and Pekosz have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

The novel coronavirus, SARS-CoV-2, remains viable in aerosols for hours and on surfaces for days, according to a new study.

The data indicate that the stability of the new virus is similar to that of SARS-CoV-1, which caused the SARS epidemic, researchers report in an article published on the medRxivpreprint server. (The posted article has been submitted for journal publication but has not been peer reviewed.)

Transmission of SARS-CoV-2, which causes COVID-19, has quickly outstripped the pace of the 2003 SARS epidemic. “Superspread” of the earlier disease arose from infection during medical procedures, in which a single infected individual seeded many secondary cases. In contrast, the novel coronavirus appears to be spread more through human-to-human transmission in a variety of settings.

However, it’s not yet known the extent to which asymptomatic or presymptomatic individuals spread the new virus through daily routine.

To investigate how long SARS-CoV-2 remains infective in the environment, Neeltje van Doremalen, PhD, of the Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, in Hamilton, Montana, and colleagues conducted simulation experiments in which they compared the viability of SARS-CoV-2 with that of SARS-CoV-1 in aerosols and on surfaces.

Among patients infected with SARS-CoV-2, viral loads in the upper respiratory tract are high; as a consequence, respiratory secretion in the form of aerosols (<5 μm) or droplets (>5 mcm) is likely, the authors note.

van Doremalen and colleagues used nebulizers to generate aerosols. Samples of SARS-CoV-1 and SARS-CoV-2 were collecting at 0, 30, 60, 120, and 180 minutes on a gelatin filter. The researchers then tested the infectivity of the viruses on Vero cells grown in culture.

They found that SARS-CoV-2 was largely stable through the full 180-minute test, with only a slight decline at 3 hours. This time course is similar to that of SARS-CoV-1; both viruses have a median half-life in aerosols of 2.7 hours (range, 1.65 hr for SARS-CoV-1, vs 7.24 hr for SARS-CoV-2).

The researchers then tested the viruses on a variety of surfaces for up to 7 days, using humidity values and temperatures designed to mimic “a variety of household and hospital situations.” The volumes of viral exposures that the team used were consistent with amounts found in the human upper and lower respiratory tracts.

For example, they applied 50 mcL of virus-containing solution to a piece of cardboard and then swabbed the surface, at different times, with an additional 1 mcL of medium. Each surface assay was replicated three times.

The novel coronavirus was most stable on plastic and stainless steel, with some virus remaining viable up to 72 hours. However, by that time the viral load had fallen by about three orders of magnitude, indicating exponential decay. This profile was remarkably similar to that of SARS-CoV-1, according to the authors.

However, the two viruses differed in staying power on copper and cardboard. No viable SARS-CoV-2 was detectable on copper after 4 hours or on cardboard after 24 hours. In contrast, SARS-CoV-1 was not viable beyond 8 hours for either copper or cardboard.

“Taken together, our results indicate that aerosol and fomite transmission of HCoV-19 [SARS-CoV-2] are plausible, as the virus can remain viable in aerosols for multiple hours and on surfaces up to days,” the authors conclude.

Andrew Pekosz, PhD, codirector of the Center of Excellence in Influenza Research and Surveillance and director of the Center for Emerging Viruses and Infectious Diseases at the Johns Hopkins Center for Global Health, Baltimore, Maryland, applauds the real-world value of the experiments.

“The PCR [polymerase chain reaction] test used [in other studies] to detect SARS-CoV-2 just detects the virus genome. It doesn’t tell you if the virus was still infectious, or ‘viable.’ That’s why this study is interesting,” Pekosz said. “It focuses on infectious virus, which is the virus that has the potential to transmit and infect another person. What we don’t know yet is how much infectious (viable) virus is needed to initiate infection in another person.”

He suggests that further investigations evaluate other types of environmental surfaces, including lacquered wood that is made into desks and ceramic tiles found in bathrooms and kitchens.

One limitation of the study is that the data for experiments on cardboard were more variable than the data for other surfaces tested.

The investigators and Pekosz have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

The novel coronavirus, SARS-CoV-2, remains viable in aerosols for hours and on surfaces for days, according to a new study.

The data indicate that the stability of the new virus is similar to that of SARS-CoV-1, which caused the SARS epidemic, researchers report in an article published on the medRxivpreprint server. (The posted article has been submitted for journal publication but has not been peer reviewed.)

Transmission of SARS-CoV-2, which causes COVID-19, has quickly outstripped the pace of the 2003 SARS epidemic. “Superspread” of the earlier disease arose from infection during medical procedures, in which a single infected individual seeded many secondary cases. In contrast, the novel coronavirus appears to be spread more through human-to-human transmission in a variety of settings.

However, it’s not yet known the extent to which asymptomatic or presymptomatic individuals spread the new virus through daily routine.

To investigate how long SARS-CoV-2 remains infective in the environment, Neeltje van Doremalen, PhD, of the Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, in Hamilton, Montana, and colleagues conducted simulation experiments in which they compared the viability of SARS-CoV-2 with that of SARS-CoV-1 in aerosols and on surfaces.

Among patients infected with SARS-CoV-2, viral loads in the upper respiratory tract are high; as a consequence, respiratory secretion in the form of aerosols (<5 μm) or droplets (>5 mcm) is likely, the authors note.

van Doremalen and colleagues used nebulizers to generate aerosols. Samples of SARS-CoV-1 and SARS-CoV-2 were collecting at 0, 30, 60, 120, and 180 minutes on a gelatin filter. The researchers then tested the infectivity of the viruses on Vero cells grown in culture.

They found that SARS-CoV-2 was largely stable through the full 180-minute test, with only a slight decline at 3 hours. This time course is similar to that of SARS-CoV-1; both viruses have a median half-life in aerosols of 2.7 hours (range, 1.65 hr for SARS-CoV-1, vs 7.24 hr for SARS-CoV-2).

The researchers then tested the viruses on a variety of surfaces for up to 7 days, using humidity values and temperatures designed to mimic “a variety of household and hospital situations.” The volumes of viral exposures that the team used were consistent with amounts found in the human upper and lower respiratory tracts.

For example, they applied 50 mcL of virus-containing solution to a piece of cardboard and then swabbed the surface, at different times, with an additional 1 mcL of medium. Each surface assay was replicated three times.

The novel coronavirus was most stable on plastic and stainless steel, with some virus remaining viable up to 72 hours. However, by that time the viral load had fallen by about three orders of magnitude, indicating exponential decay. This profile was remarkably similar to that of SARS-CoV-1, according to the authors.

However, the two viruses differed in staying power on copper and cardboard. No viable SARS-CoV-2 was detectable on copper after 4 hours or on cardboard after 24 hours. In contrast, SARS-CoV-1 was not viable beyond 8 hours for either copper or cardboard.

“Taken together, our results indicate that aerosol and fomite transmission of HCoV-19 [SARS-CoV-2] are plausible, as the virus can remain viable in aerosols for multiple hours and on surfaces up to days,” the authors conclude.

Andrew Pekosz, PhD, codirector of the Center of Excellence in Influenza Research and Surveillance and director of the Center for Emerging Viruses and Infectious Diseases at the Johns Hopkins Center for Global Health, Baltimore, Maryland, applauds the real-world value of the experiments.

“The PCR [polymerase chain reaction] test used [in other studies] to detect SARS-CoV-2 just detects the virus genome. It doesn’t tell you if the virus was still infectious, or ‘viable.’ That’s why this study is interesting,” Pekosz said. “It focuses on infectious virus, which is the virus that has the potential to transmit and infect another person. What we don’t know yet is how much infectious (viable) virus is needed to initiate infection in another person.”

He suggests that further investigations evaluate other types of environmental surfaces, including lacquered wood that is made into desks and ceramic tiles found in bathrooms and kitchens.

One limitation of the study is that the data for experiments on cardboard were more variable than the data for other surfaces tested.

The investigators and Pekosz have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

The novel coronavirus (2019-nCoV) shows evidence of causing gastrointestinal symptoms and has the potential to be transmitted by the fecal-oral route, according to a new report from physicians at Shanghai Jiao Tong University, published online (Gastroenterology. 2020 March 3. doi: 10.1053/j.gastro.2020.02.054).

The virus’s respiratory symptoms are well documented and suggest primary transmission by droplet or contact, while other symptoms such as diarrhea, nausea, vomiting, and abdominal discomfort are less common and appear to vary between populations. The SARS coronavirus showed up in stool, even sometimes in patients discharged from the hospital. In a study of hospitalized patients in Wuhan, China, 10.1% of coronavirus patients had diarrhea and nausea in the 1-2 days before onset of fever and dyspnea. The first U.S. patient to be diagnosed had a 2-day history of nausea and vomiting, and had a loose bowel movement on the second day in the hospital. Clinicians later confirmed the presence of viral RNA in both the patient’s stool and airway.

The authors say that researchers in China have isolated viral RNA from the stool of two patients (unpublished), and it has been found in saliva, suggesting the possibility of the salivary gland as an infection or transmission route.

The authors maintain that previous studies likely overlooked or neglected patients who had mild intestinal symptoms. “Many efforts should be made to be alert on the initial digestive symptoms of COVID-19 for early detection, early diagnosis, early isolation and early intervention,” the authors wrote.

Like other coronaviruses, it appears that 2019-nCoV infects cells through an interaction between viral transmembrane spike glycoprotein (S-protein) receptor-binding domain, and the cell receptors angiotensin-converting enzyme 2 (ACE-2) and host cellular transmembrane serine protease (TMPRSS). Transcriptome analysis has shown that human lung AT2 cells express ACE-2 and TMPRSS, but esophagus upper and stratified epithelial cells also express both factors, as do stratified epithelial cells and absorptive enterocytes in the ileum and colon.

The researchers call for investigation into ACE-2 fusion proteins and TMPRSS inhibitors for diagnosis, prophylaxis, or treatment of COVID-19.

The authors also noted that COVID-19 has been linked to mild to moderate liver injury as revealed by elevated aminotransferases, hypoproteinemia and prothrombin time prolongation. This also has precedent in that the SARS coronavirus can infect the liver, and biopsies revealed mitoses and apoptosis, along with other abnormalities. SARS-associated hepatitis may be the result of viral hepatitis, immune overreaction, or a secondary effect of antiviral medications or other drugs. Little is known to date about the ability of 2019-nCoV to infect the liver, but single-cell RNA sequencing data from two distinct cohorts showed more ACE-2 expression in cholangiocytes (59.7%) than hepatocytes (2.6%), which indicates that the virus might directly affect intrahepatic bile ducts.

The authors had no sources of funding or financial conflicts.

SOURCE: GU J et al. Gastroenterology. 2020 March 3. doi: 10.1053/j.gastro.2020.02.054.

*This story was updated on 4/10.2020.

The novel coronavirus (2019-nCoV) shows evidence of causing gastrointestinal symptoms and has the potential to be transmitted by the fecal-oral route, according to a new report from physicians at Shanghai Jiao Tong University, published online (Gastroenterology. 2020 March 3. doi: 10.1053/j.gastro.2020.02.054).

The virus’s respiratory symptoms are well documented and suggest primary transmission by droplet or contact, while other symptoms such as diarrhea, nausea, vomiting, and abdominal discomfort are less common and appear to vary between populations. The SARS coronavirus showed up in stool, even sometimes in patients discharged from the hospital. In a study of hospitalized patients in Wuhan, China, 10.1% of coronavirus patients had diarrhea and nausea in the 1-2 days before onset of fever and dyspnea. The first U.S. patient to be diagnosed had a 2-day history of nausea and vomiting, and had a loose bowel movement on the second day in the hospital. Clinicians later confirmed the presence of viral RNA in both the patient’s stool and airway.

The authors say that researchers in China have isolated viral RNA from the stool of two patients (unpublished), and it has been found in saliva, suggesting the possibility of the salivary gland as an infection or transmission route.

The authors maintain that previous studies likely overlooked or neglected patients who had mild intestinal symptoms. “Many efforts should be made to be alert on the initial digestive symptoms of COVID-19 for early detection, early diagnosis, early isolation and early intervention,” the authors wrote.

Like other coronaviruses, it appears that 2019-nCoV infects cells through an interaction between viral transmembrane spike glycoprotein (S-protein) receptor-binding domain, and the cell receptors angiotensin-converting enzyme 2 (ACE-2) and host cellular transmembrane serine protease (TMPRSS). Transcriptome analysis has shown that human lung AT2 cells express ACE-2 and TMPRSS, but esophagus upper and stratified epithelial cells also express both factors, as do stratified epithelial cells and absorptive enterocytes in the ileum and colon.

The researchers call for investigation into ACE-2 fusion proteins and TMPRSS inhibitors for diagnosis, prophylaxis, or treatment of COVID-19.

The authors also noted that COVID-19 has been linked to mild to moderate liver injury as revealed by elevated aminotransferases, hypoproteinemia and prothrombin time prolongation. This also has precedent in that the SARS coronavirus can infect the liver, and biopsies revealed mitoses and apoptosis, along with other abnormalities. SARS-associated hepatitis may be the result of viral hepatitis, immune overreaction, or a secondary effect of antiviral medications or other drugs. Little is known to date about the ability of 2019-nCoV to infect the liver, but single-cell RNA sequencing data from two distinct cohorts showed more ACE-2 expression in cholangiocytes (59.7%) than hepatocytes (2.6%), which indicates that the virus might directly affect intrahepatic bile ducts.

The authors had no sources of funding or financial conflicts.

SOURCE: GU J et al. Gastroenterology. 2020 March 3. doi: 10.1053/j.gastro.2020.02.054.

*This story was updated on 4/10.2020.

The novel coronavirus (2019-nCoV) shows evidence of causing gastrointestinal symptoms and has the potential to be transmitted by the fecal-oral route, according to a new report from physicians at Shanghai Jiao Tong University, published online (Gastroenterology. 2020 March 3. doi: 10.1053/j.gastro.2020.02.054).

The virus’s respiratory symptoms are well documented and suggest primary transmission by droplet or contact, while other symptoms such as diarrhea, nausea, vomiting, and abdominal discomfort are less common and appear to vary between populations. The SARS coronavirus showed up in stool, even sometimes in patients discharged from the hospital. In a study of hospitalized patients in Wuhan, China, 10.1% of coronavirus patients had diarrhea and nausea in the 1-2 days before onset of fever and dyspnea. The first U.S. patient to be diagnosed had a 2-day history of nausea and vomiting, and had a loose bowel movement on the second day in the hospital. Clinicians later confirmed the presence of viral RNA in both the patient’s stool and airway.

The authors say that researchers in China have isolated viral RNA from the stool of two patients (unpublished), and it has been found in saliva, suggesting the possibility of the salivary gland as an infection or transmission route.

The authors maintain that previous studies likely overlooked or neglected patients who had mild intestinal symptoms. “Many efforts should be made to be alert on the initial digestive symptoms of COVID-19 for early detection, early diagnosis, early isolation and early intervention,” the authors wrote.

Like other coronaviruses, it appears that 2019-nCoV infects cells through an interaction between viral transmembrane spike glycoprotein (S-protein) receptor-binding domain, and the cell receptors angiotensin-converting enzyme 2 (ACE-2) and host cellular transmembrane serine protease (TMPRSS). Transcriptome analysis has shown that human lung AT2 cells express ACE-2 and TMPRSS, but esophagus upper and stratified epithelial cells also express both factors, as do stratified epithelial cells and absorptive enterocytes in the ileum and colon.

The researchers call for investigation into ACE-2 fusion proteins and TMPRSS inhibitors for diagnosis, prophylaxis, or treatment of COVID-19.

The authors also noted that COVID-19 has been linked to mild to moderate liver injury as revealed by elevated aminotransferases, hypoproteinemia and prothrombin time prolongation. This also has precedent in that the SARS coronavirus can infect the liver, and biopsies revealed mitoses and apoptosis, along with other abnormalities. SARS-associated hepatitis may be the result of viral hepatitis, immune overreaction, or a secondary effect of antiviral medications or other drugs. Little is known to date about the ability of 2019-nCoV to infect the liver, but single-cell RNA sequencing data from two distinct cohorts showed more ACE-2 expression in cholangiocytes (59.7%) than hepatocytes (2.6%), which indicates that the virus might directly affect intrahepatic bile ducts.

The authors had no sources of funding or financial conflicts.

SOURCE: GU J et al. Gastroenterology. 2020 March 3. doi: 10.1053/j.gastro.2020.02.054.

*This story was updated on 4/10.2020.

The Get With the Guidelines – Stroke program is finally turning its attention to hemorrhagic strokes after having spurred improved patient management performance from participating U.S. stroke centers since its start in 2003 with a focus on acute ischemic stroke.

The advisers who craft policy for Get With the Guidelines – Stroke (GWTG–S) are planning to launch a pilot program later in 2020 that will initiate data monitoring and quality improvement aimed at optimizing care for patients following an intracerebral hemorrhage (ICH) starting at 15 U.S. stroke centers, with announcement of these 15 participating centers expected later in 2020. The program will start by targeting nine specific, evidence-based, key aspects of the acute management of ICH patients, said Kevin N. Sheth, MD, professor of neurology and neurosurgery, and chief of neurocritical care and emergency neurology at Yale University in New Haven, Conn, and a volunteer expert who is part of the team developing the ICH initiative.

According to Dr. Sheth, the nine imperatives of acute ICH care that the program plans to monitor at participating centers are:

• Obtain a baseline severity score.
• Identify etiology as spontaneous or treatment related.
• Perform coagulopathy reversal or anticoagulant reversal.
• Administer venous thromboembolism prophylaxis.
• Apply dysphagia screening within 24 hours, and delay oral intake until patient passes dysphagia screen.
• Provide patient management in a multidisciplinary stroke or ICU unit.
• Prescribe appropriate blood pressure treatment at discharge.
• Perform assessment for rehabilitation.
• Avoid prescribing corticosteroids and other contraindicated drugs.

GWTG–S is adopting these metrics for assessing the acute care of ICH patients based largely on the recommendations of an expert 2018 panel organized by the American Heart Association and American Stroke. Association that proposed a set of performance measures for the care of ICH patients. This set of performance measures served as the primary basis for designing the new GWTG–S program, along with considerations of feasibility for collecting data on these measures, Dr. Sheth said in an interview. “We hope to make it easy” for centers to collect the data needed to participate.

The existing GWTG–S program is now 17-years old, and has spread to nearly 2,400 U.S. stroke centers as of early 2020, but the time has come to broaden its reach to patients with ICH and the programs that treat these patients, Dr. Sheth said. After years of nihilism about the prospects for patients following an ICH stroke, survival rates have increased, presenting “an opportunity to optimize care, for quality improvement,” he explained. “It’s a huge shift.” ICH patients “do better than we used to think.”

[email protected]

The Get With the Guidelines – Stroke program is finally turning its attention to hemorrhagic strokes after having spurred improved patient management performance from participating U.S. stroke centers since its start in 2003 with a focus on acute ischemic stroke.

The advisers who craft policy for Get With the Guidelines – Stroke (GWTG–S) are planning to launch a pilot program later in 2020 that will initiate data monitoring and quality improvement aimed at optimizing care for patients following an intracerebral hemorrhage (ICH) starting at 15 U.S. stroke centers, with announcement of these 15 participating centers expected later in 2020. The program will start by targeting nine specific, evidence-based, key aspects of the acute management of ICH patients, said Kevin N. Sheth, MD, professor of neurology and neurosurgery, and chief of neurocritical care and emergency neurology at Yale University in New Haven, Conn, and a volunteer expert who is part of the team developing the ICH initiative.

According to Dr. Sheth, the nine imperatives of acute ICH care that the program plans to monitor at participating centers are:

• Obtain a baseline severity score.
• Identify etiology as spontaneous or treatment related.
• Perform coagulopathy reversal or anticoagulant reversal.
• Administer venous thromboembolism prophylaxis.
• Apply dysphagia screening within 24 hours, and delay oral intake until patient passes dysphagia screen.
• Provide patient management in a multidisciplinary stroke or ICU unit.
• Prescribe appropriate blood pressure treatment at discharge.
• Perform assessment for rehabilitation.
• Avoid prescribing corticosteroids and other contraindicated drugs.

GWTG–S is adopting these metrics for assessing the acute care of ICH patients based largely on the recommendations of an expert 2018 panel organized by the American Heart Association and American Stroke. Association that proposed a set of performance measures for the care of ICH patients. This set of performance measures served as the primary basis for designing the new GWTG–S program, along with considerations of feasibility for collecting data on these measures, Dr. Sheth said in an interview. “We hope to make it easy” for centers to collect the data needed to participate.

The existing GWTG–S program is now 17-years old, and has spread to nearly 2,400 U.S. stroke centers as of early 2020, but the time has come to broaden its reach to patients with ICH and the programs that treat these patients, Dr. Sheth said. After years of nihilism about the prospects for patients following an ICH stroke, survival rates have increased, presenting “an opportunity to optimize care, for quality improvement,” he explained. “It’s a huge shift.” ICH patients “do better than we used to think.”

[email protected]

The Get With the Guidelines – Stroke program is finally turning its attention to hemorrhagic strokes after having spurred improved patient management performance from participating U.S. stroke centers since its start in 2003 with a focus on acute ischemic stroke.

The advisers who craft policy for Get With the Guidelines – Stroke (GWTG–S) are planning to launch a pilot program later in 2020 that will initiate data monitoring and quality improvement aimed at optimizing care for patients following an intracerebral hemorrhage (ICH) starting at 15 U.S. stroke centers, with announcement of these 15 participating centers expected later in 2020. The program will start by targeting nine specific, evidence-based, key aspects of the acute management of ICH patients, said Kevin N. Sheth, MD, professor of neurology and neurosurgery, and chief of neurocritical care and emergency neurology at Yale University in New Haven, Conn, and a volunteer expert who is part of the team developing the ICH initiative.

According to Dr. Sheth, the nine imperatives of acute ICH care that the program plans to monitor at participating centers are:

• Obtain a baseline severity score.
• Identify etiology as spontaneous or treatment related.
• Perform coagulopathy reversal or anticoagulant reversal.
• Administer venous thromboembolism prophylaxis.
• Apply dysphagia screening within 24 hours, and delay oral intake until patient passes dysphagia screen.
• Provide patient management in a multidisciplinary stroke or ICU unit.
• Prescribe appropriate blood pressure treatment at discharge.
• Perform assessment for rehabilitation.
• Avoid prescribing corticosteroids and other contraindicated drugs.

GWTG–S is adopting these metrics for assessing the acute care of ICH patients based largely on the recommendations of an expert 2018 panel organized by the American Heart Association and American Stroke. Association that proposed a set of performance measures for the care of ICH patients. This set of performance measures served as the primary basis for designing the new GWTG–S program, along with considerations of feasibility for collecting data on these measures, Dr. Sheth said in an interview. “We hope to make it easy” for centers to collect the data needed to participate.

The existing GWTG–S program is now 17-years old, and has spread to nearly 2,400 U.S. stroke centers as of early 2020, but the time has come to broaden its reach to patients with ICH and the programs that treat these patients, Dr. Sheth said. After years of nihilism about the prospects for patients following an ICH stroke, survival rates have increased, presenting “an opportunity to optimize care, for quality improvement,” he explained. “It’s a huge shift.” ICH patients “do better than we used to think.”

[email protected]

Ideally, all cases of colorectal cancer would be detected at an early and curable stage, but, as new guidelines for late-stage colorectal cancer suggest, the world is far from perfect.

“Different regions of the world, both among and within countries, differ with respect to access to early detection,” the guideline authors wrote in JCO Global Oncology. “Many regions do not have mass or even opportunistic screening, and even within regions with mass screening, subpopulations may not have access to screening.”

The guidelines were developed by the American Society of Clinical Oncology’s Resource-Stratified Guidelines Advisory Group. Based on and adapted from existing guidelines developed by four international agencies, the ASCO guidelines take into account economic and social realities and offer recommendations for diagnosis, staging, and treatment by resource level: basic, limited, enhanced, or maximal.

“We made these guidelines to apply to countries or regions that have basic resources,” lead author E. Gabriela Chiorean, MD, of the University of Washington, Seattle, and the Seattle Cancer Care Alliance, said in an interview.

“We decided what should be the most basic resources – diagnostics, imaging, and treatment – that should be available to patients, and we make recommendations for the use of limited resources and supplies,” she added.

The guidelines pose and answer seven questions about optimal initial symptom management, diagnosis, and staging; optimal first and later lines of therapy; liver-directed therapy options for patients with late-stage colorectal cancer and liver metastases; and optimal on-treatment surveillance and follow-up strategies for patients treated for metastatic colorectal cancer.

For each question, the document offers guidance based on the availability of resources. As defined by the authors, the recommendations are stratified according to the following categories:

• Basic resources – “Core resources or fundamental services that are absolutely necessary for any cancer health care system to function.”
• Limited resources – “Second-tier resources or services that are intended to produce major improvements in outcome, such as increased survival and cost effectiveness, and are attainable with limited financial means and modest infrastructure.”
• Enhanced resources – “Third-tier resources or services that are optional but important; enhanced-level resources should produce further improvements in outcome and increase the number and quality of options and patient choice.”
• Maximal resources – “High-level/state-of-the art resources or services that may be used/available in some high-resource regions and/or may be recommended by high-resource setting guidelines that do not adapt to resource constraints but that nonetheless should be considered a lower priority than those resources or services listed in the other categories on the basis of extreme cost and/or impracticality for broad use in a resource-limited environment.”

The guidelines address common elements of symptom management for patients with acute disease, such as diagnosis involving the primary tumor, endoscopy when possible, and staging to include digital rectal exam and/or imaging when possible. The guidelines also include information tailored to resource level about chemotherapy and surgical resection.

“If, for example, a patient presents with bleeding and you suspect it to be of colorectal origin, we make recommendations that if the patient has symptoms of obstruction and bleeding and is resectable, they should undergo surgery, which should be available in countries of all resource levels,” Dr. Chiorean said.

The guidelines also recommend following the ASCO palliative care guidelines (J Clin Oncol. 2017 Jan;35[1]:96-112) for those patients who present with clinically unstable disease because of bowel obstruction, uncontrolled bleeding, or uncontrolled pain. Patients with clinically stable disease and ongoing bleeding from the primary tumor site are recommended to undergo transfusion and primary-site resection if only basic resources are available or transfusion plus multidisciplinary specialized evaluation when higher-level resources are available.

The ASCO guidelines are adapted from guidelines developed by Cancer Council Australia; the European Society for Medical Oncology; the National Institute for Health and Care Excellence, including separate recommendation for therapy combinations (https://www.nice.org.uk/guidance/ta212, https://www.nice.org.uk/guidance/ta439); and the National Comprehensive Cancer Network. Some of these guidelines have been updated since the creation of the ASCO guidelines.

ASCO funds the guideline development process. Dr. Chiorean and other authors disclosed relationships with multiple companies.

SOURCE: Chiorean EG et al. JCO Glob Oncol. 2020 Mar;6:414-38.

Ideally, all cases of colorectal cancer would be detected at an early and curable stage, but, as new guidelines for late-stage colorectal cancer suggest, the world is far from perfect.

“Different regions of the world, both among and within countries, differ with respect to access to early detection,” the guideline authors wrote in JCO Global Oncology. “Many regions do not have mass or even opportunistic screening, and even within regions with mass screening, subpopulations may not have access to screening.”

The guidelines were developed by the American Society of Clinical Oncology’s Resource-Stratified Guidelines Advisory Group. Based on and adapted from existing guidelines developed by four international agencies, the ASCO guidelines take into account economic and social realities and offer recommendations for diagnosis, staging, and treatment by resource level: basic, limited, enhanced, or maximal.

“We made these guidelines to apply to countries or regions that have basic resources,” lead author E. Gabriela Chiorean, MD, of the University of Washington, Seattle, and the Seattle Cancer Care Alliance, said in an interview.

“We decided what should be the most basic resources – diagnostics, imaging, and treatment – that should be available to patients, and we make recommendations for the use of limited resources and supplies,” she added.

The guidelines pose and answer seven questions about optimal initial symptom management, diagnosis, and staging; optimal first and later lines of therapy; liver-directed therapy options for patients with late-stage colorectal cancer and liver metastases; and optimal on-treatment surveillance and follow-up strategies for patients treated for metastatic colorectal cancer.

For each question, the document offers guidance based on the availability of resources. As defined by the authors, the recommendations are stratified according to the following categories:

• Basic resources – “Core resources or fundamental services that are absolutely necessary for any cancer health care system to function.”
• Limited resources – “Second-tier resources or services that are intended to produce major improvements in outcome, such as increased survival and cost effectiveness, and are attainable with limited financial means and modest infrastructure.”
• Enhanced resources – “Third-tier resources or services that are optional but important; enhanced-level resources should produce further improvements in outcome and increase the number and quality of options and patient choice.”
• Maximal resources – “High-level/state-of-the art resources or services that may be used/available in some high-resource regions and/or may be recommended by high-resource setting guidelines that do not adapt to resource constraints but that nonetheless should be considered a lower priority than those resources or services listed in the other categories on the basis of extreme cost and/or impracticality for broad use in a resource-limited environment.”

The guidelines address common elements of symptom management for patients with acute disease, such as diagnosis involving the primary tumor, endoscopy when possible, and staging to include digital rectal exam and/or imaging when possible. The guidelines also include information tailored to resource level about chemotherapy and surgical resection.

“If, for example, a patient presents with bleeding and you suspect it to be of colorectal origin, we make recommendations that if the patient has symptoms of obstruction and bleeding and is resectable, they should undergo surgery, which should be available in countries of all resource levels,” Dr. Chiorean said.

The guidelines also recommend following the ASCO palliative care guidelines (J Clin Oncol. 2017 Jan;35[1]:96-112) for those patients who present with clinically unstable disease because of bowel obstruction, uncontrolled bleeding, or uncontrolled pain. Patients with clinically stable disease and ongoing bleeding from the primary tumor site are recommended to undergo transfusion and primary-site resection if only basic resources are available or transfusion plus multidisciplinary specialized evaluation when higher-level resources are available.

The ASCO guidelines are adapted from guidelines developed by Cancer Council Australia; the European Society for Medical Oncology; the National Institute for Health and Care Excellence, including separate recommendation for therapy combinations (https://www.nice.org.uk/guidance/ta212, https://www.nice.org.uk/guidance/ta439); and the National Comprehensive Cancer Network. Some of these guidelines have been updated since the creation of the ASCO guidelines.

ASCO funds the guideline development process. Dr. Chiorean and other authors disclosed relationships with multiple companies.

SOURCE: Chiorean EG et al. JCO Glob Oncol. 2020 Mar;6:414-38.

Ideally, all cases of colorectal cancer would be detected at an early and curable stage, but, as new guidelines for late-stage colorectal cancer suggest, the world is far from perfect.

“Different regions of the world, both among and within countries, differ with respect to access to early detection,” the guideline authors wrote in JCO Global Oncology. “Many regions do not have mass or even opportunistic screening, and even within regions with mass screening, subpopulations may not have access to screening.”

The guidelines were developed by the American Society of Clinical Oncology’s Resource-Stratified Guidelines Advisory Group. Based on and adapted from existing guidelines developed by four international agencies, the ASCO guidelines take into account economic and social realities and offer recommendations for diagnosis, staging, and treatment by resource level: basic, limited, enhanced, or maximal.

“We made these guidelines to apply to countries or regions that have basic resources,” lead author E. Gabriela Chiorean, MD, of the University of Washington, Seattle, and the Seattle Cancer Care Alliance, said in an interview.

“We decided what should be the most basic resources – diagnostics, imaging, and treatment – that should be available to patients, and we make recommendations for the use of limited resources and supplies,” she added.

The guidelines pose and answer seven questions about optimal initial symptom management, diagnosis, and staging; optimal first and later lines of therapy; liver-directed therapy options for patients with late-stage colorectal cancer and liver metastases; and optimal on-treatment surveillance and follow-up strategies for patients treated for metastatic colorectal cancer.

For each question, the document offers guidance based on the availability of resources. As defined by the authors, the recommendations are stratified according to the following categories:

• Basic resources – “Core resources or fundamental services that are absolutely necessary for any cancer health care system to function.”
• Limited resources – “Second-tier resources or services that are intended to produce major improvements in outcome, such as increased survival and cost effectiveness, and are attainable with limited financial means and modest infrastructure.”
• Enhanced resources – “Third-tier resources or services that are optional but important; enhanced-level resources should produce further improvements in outcome and increase the number and quality of options and patient choice.”
• Maximal resources – “High-level/state-of-the art resources or services that may be used/available in some high-resource regions and/or may be recommended by high-resource setting guidelines that do not adapt to resource constraints but that nonetheless should be considered a lower priority than those resources or services listed in the other categories on the basis of extreme cost and/or impracticality for broad use in a resource-limited environment.”

The guidelines address common elements of symptom management for patients with acute disease, such as diagnosis involving the primary tumor, endoscopy when possible, and staging to include digital rectal exam and/or imaging when possible. The guidelines also include information tailored to resource level about chemotherapy and surgical resection.

“If, for example, a patient presents with bleeding and you suspect it to be of colorectal origin, we make recommendations that if the patient has symptoms of obstruction and bleeding and is resectable, they should undergo surgery, which should be available in countries of all resource levels,” Dr. Chiorean said.

The guidelines also recommend following the ASCO palliative care guidelines (J Clin Oncol. 2017 Jan;35[1]:96-112) for those patients who present with clinically unstable disease because of bowel obstruction, uncontrolled bleeding, or uncontrolled pain. Patients with clinically stable disease and ongoing bleeding from the primary tumor site are recommended to undergo transfusion and primary-site resection if only basic resources are available or transfusion plus multidisciplinary specialized evaluation when higher-level resources are available.

The ASCO guidelines are adapted from guidelines developed by Cancer Council Australia; the European Society for Medical Oncology; the National Institute for Health and Care Excellence, including separate recommendation for therapy combinations (https://www.nice.org.uk/guidance/ta212, https://www.nice.org.uk/guidance/ta439); and the National Comprehensive Cancer Network. Some of these guidelines have been updated since the creation of the ASCO guidelines.

ASCO funds the guideline development process. Dr. Chiorean and other authors disclosed relationships with multiple companies.

SOURCE: Chiorean EG et al. JCO Glob Oncol. 2020 Mar;6:414-38.

Patients with diabetes may be at extra risk for coronavirus disease (COVID-19) mortality, and doctors treating them need to keep up with the latest guidelines and expert advice.

Most health advisories about COVID-19 mention diabetes as one of the high-risk categories for the disease, likely because early data coming out of China, where the disease was first reported, indicated an elevated case-fatality rate for COVID-19 patients who also had diabetes.

In an article published in JAMA, Zunyou Wu, MD, and Jennifer M. McGoogan, PhD, summarized the findings from a February report on 44,672 confirmed cases of the disease from the Chinese Center for Disease Control and Prevention. The overall case-fatality rate (CFR) at that stage was 2.3% (1,023 deaths of the 44,672 confirmed cases). The data indicated that the CFR was elevated among COVID-19 patients with preexisting comorbid conditions, specifically, cardiovascular disease (CFR, 10.5%), diabetes (7.3%), chronic respiratory disease (6.3%), hypertension (6%), and cancer (5.6%).

The data also showed an aged-related trend in the CFR, with patients aged 80 years or older having a CFR of 14.8% and those aged 70-79 years, a rate of 8.0%, while there were no fatal cases reported in patients aged 9 years or younger (JAMA. 2020 Feb 24. doi: 10.1001/jama.2020.2648).

Those findings have been echoed by the U.S. Centers of Disease Control and Prevention. The American Diabetes Association and the American Association of Clinical Endocrinologists have in turn referenced the CDC in their COVID-19 guidance recommendations for patients with diabetes.

Guidelines were already in place for treatment of infections in patients with diabetes, and at this stage, it seems that the same guidelines would extend to those patients who are also diagnosed with COVID-19, which is caused by the novel coronavirus, SARS-CoV-2.

In general, patients with diabetes – especially those whose disease is not controlled, or not well controlled – can be more susceptible to more common infections, such as influenza and pneumonia, possibly because hyperglycemia can subdue immunity by disrupting function of the white blood cells.
 

Glucose control is key

An important factor in any form of infection control in patients with diabetes seems to be whether or not a patient’s glucose levels are well controlled, according to comments from members of the editorial advisory board for Clinical Endocrinology News. Good glucose control, therefore, could be instrumental in reducing both the risk for and severity of infection.

Paul Jellinger, MD, of the Center for Diabetes & Endocrine Care, Hollywood, Fla., said that, over the years, he had not observed higher infection rates in general in patients with hemoglobin A_1c levels below 7, or even higher. However, “a bigger question for me, given the broad category of ‘diabetes’ listed as a risk for serious coronavirus complications by the CDC, has been: Just which individuals with diabetes are really at risk? Are patients with well-controlled diabetes at increased risk as much as those with significant hyperglycemia and uncontrolled diabetes? In my view, not likely.”

Alan Jay Cohen, MD, agreed with Dr. Jellinger. “Many patients have called the office in the last 10 days to ask if there are special precautions they should take because they are reading that they are in the high-risk group because they have diabetes. Many of them are in superb, or at least pretty good, control. I have not seen where they have had a higher incidence of infection than the general population, and I have not seen data with COVID-19 that specifically demonstrates that a person with diabetes in good control has an increased risk,” he said.

“My recommendations to these patients have been the same as those given to the general population,” added Dr. Cohen, medical director at Baptist Medical Group: The Endocrine Clinic, Memphis.

Herbert I. Rettinger, MD, also conceded that poorly controlled blood sugars and confounding illnesses, such as renal and cardiac conditions, are common in patients with long-standing diabetes, but “there is a huge population of patients with type 1 diabetes, and very few seem to be more susceptible to infection. Perhaps I am missing those with poor diet and glucose control.”

Philip Levy, MD, picked up on that latter point, emphasizing that “endocrinologists take care of fewer patients with diabetes than do primary care physicians. Most patients with type 2 diabetes are not seen by us unless the PCP has problems [treating them],” so it could be that PCPs may see a higher number of patients who are at a greater risk for infections.

Ultimately, “good glucose control is very helpful in avoiding infections,” said Dr. Levy, of the Banner University Medical Group Endocrinology & Diabetes, Phoenix.
 

For sick patients

Guidelines for patients at the Joslin Diabetes Center in Boston advise patients who are feeling sick to continue taking their diabetes medications, unless instructed otherwise by their providers, and to monitor their glucose more frequently because it can spike suddenly.

Patients with type 1 diabetes should check for ketones if their glucose passes 250 mg/dL, according to the guidelines, and patients should remain hydrated at all times and get plenty of rest.

“Sick-day guidelines definitely apply, but patients should be advised to get tested if they have any symptoms they are concerned about,” said Dr. Rettinger, of the Endocrinology Medical Group of Orange County, Orange, Calif.

If patients with diabetes develop COVID-19, then home management may still be possible, according to Ritesh Gupta, MD, of Fortis C-DOC Hospital, New Delhi, and colleagues (Diabetes Metab Syndr. 2020 Mar 10;14[3]:211-2. doi: 10.1016/j.dsx.2020.03.002).

Dr. Rettinger agreed, noting that home management would be feasible as long as “everything is going well, that is, the patient is not experiencing respiratory problems or difficulties in controlling glucose levels. Consider patients with type 1 diabetes who have COVID-19 as you would a nursing home patient – ever vigilant.”

Dr. Gupta and coauthors also recommended basic treatment measures such as maintaining hydration and managing symptoms with acetaminophen and steam inhalation, and home isolation for 14 days or until the symptoms resolve. However, the ADA warns in its guidelines that patients should “be aware that some constant glucose monitoring sensors (Dexcom G5, Medtronic Enlite, and Guardian) are impacted by acetaminophen (Tylenol), and that patients should check with finger sticks to ensure accuracy [if they are taking acetaminophen].”

In the event of hyperglycemia with fever in patients with type 1 diabetes, blood glucose and urinary ketones should be monitored often, the authors wrote, cautioning that “frequent changes in dosage and correctional bolus may be required to maintain normoglycemia.” Dr Rettinger emphasized that “hyperglycemia, as always, is best treated with fluids and insulin and frequent checks of sugars to be sure the treatment regimen is successful.”

In regard to diabetic drug regimens, patients with type 1 or 2 disease should continue on their current medications, advised Yehuda Handelsman, MD. “Some, especially those on insulin, may require more of it. And the patient should increase fluid intake to prevent fluid depletion. We do not reduce antihyperglycemic medication to preserve fluids.

Preventive measures

In the interest of maintaining good glucose control, patients also should monitor their glucose levels more frequently so that fluctuations can be detected early and quickly addressed with the appropriate medication adjustments, according to guidelines from the ADA and AACE. They should continue to follow a healthy diet that includes adequate protein and they should exercise regularly.

Patients should ensure that they have enough medication and testing supplies – for at least 14 days, and longer, if costs permit – in case they have to go into quarantine.

General preventive measures, such as frequent hand washing with soap and water, practicing good respiratory hygiene by sneezing or coughing into a facial tissue or bent elbow, also apply for reducing the risk of infection. Touching of the face should be avoided, as should nonessential travel and contact with infected individuals.

Patients with diabetes should always be current with their influenza and pneumonia shots.

Dr. Rettinger said that he always recommends the following preventative measures to his patients and he is using the current health crisis to reinforce them:

• Eat lots of multicolored fruits and vegetables.
• Eat yogurt and take probiotics to keep the intestinal biome strong and functional.
• Be extra vigilant regarding sugars and sugar control to avoid peaks and valleys wherever possible.
• Keep the immune system strong with at least 7-8 hours sleep and reduce stress levels whenever possible.
• Avoid crowds and handshaking.
• Wash hands regularly.

Possible therapies

There are currently no drugs that have been approved specifically for the treatment of COVID-19, although a vaccine against the disease is currently under development.

Dr. Gupta and his colleagues noted in their article that there have been reports of the anecdotal use of antiviral drugs such as lopinavir, ritonavir, interferon-beta, the RNA polymerase inhibitor remdesivir, and chloroquine.

However, Dr. Handelsman said that, as far as he knows, none of these drugs has been shown to be beneficial for COVID-19. “Some [providers] have tried Tamiflu, but with no clear outcomes, and for severely sick patients, they tried medications for anti-HIV, hepatitis C, and malaria, but so far, there has been no breakthrough.”

Dr. Cohen, Dr. Handelsman, Dr. Jellinger, Dr. Levy, and Dr. Rettinger are members of the editorial advisory board of Clinical Endocrinology News. Dr. Gupta and Dr. Wu, and their colleagues, reported no conflicts of interest.

[email protected]

Patients with diabetes may be at extra risk for coronavirus disease (COVID-19) mortality, and doctors treating them need to keep up with the latest guidelines and expert advice.

Most health advisories about COVID-19 mention diabetes as one of the high-risk categories for the disease, likely because early data coming out of China, where the disease was first reported, indicated an elevated case-fatality rate for COVID-19 patients who also had diabetes.

In an article published in JAMA, Zunyou Wu, MD, and Jennifer M. McGoogan, PhD, summarized the findings from a February report on 44,672 confirmed cases of the disease from the Chinese Center for Disease Control and Prevention. The overall case-fatality rate (CFR) at that stage was 2.3% (1,023 deaths of the 44,672 confirmed cases). The data indicated that the CFR was elevated among COVID-19 patients with preexisting comorbid conditions, specifically, cardiovascular disease (CFR, 10.5%), diabetes (7.3%), chronic respiratory disease (6.3%), hypertension (6%), and cancer (5.6%).

The data also showed an aged-related trend in the CFR, with patients aged 80 years or older having a CFR of 14.8% and those aged 70-79 years, a rate of 8.0%, while there were no fatal cases reported in patients aged 9 years or younger (JAMA. 2020 Feb 24. doi: 10.1001/jama.2020.2648).

Those findings have been echoed by the U.S. Centers of Disease Control and Prevention. The American Diabetes Association and the American Association of Clinical Endocrinologists have in turn referenced the CDC in their COVID-19 guidance recommendations for patients with diabetes.

Guidelines were already in place for treatment of infections in patients with diabetes, and at this stage, it seems that the same guidelines would extend to those patients who are also diagnosed with COVID-19, which is caused by the novel coronavirus, SARS-CoV-2.

In general, patients with diabetes – especially those whose disease is not controlled, or not well controlled – can be more susceptible to more common infections, such as influenza and pneumonia, possibly because hyperglycemia can subdue immunity by disrupting function of the white blood cells.
 

Glucose control is key

An important factor in any form of infection control in patients with diabetes seems to be whether or not a patient’s glucose levels are well controlled, according to comments from members of the editorial advisory board for Clinical Endocrinology News. Good glucose control, therefore, could be instrumental in reducing both the risk for and severity of infection.

Paul Jellinger, MD, of the Center for Diabetes & Endocrine Care, Hollywood, Fla., said that, over the years, he had not observed higher infection rates in general in patients with hemoglobin A_1c levels below 7, or even higher. However, “a bigger question for me, given the broad category of ‘diabetes’ listed as a risk for serious coronavirus complications by the CDC, has been: Just which individuals with diabetes are really at risk? Are patients with well-controlled diabetes at increased risk as much as those with significant hyperglycemia and uncontrolled diabetes? In my view, not likely.”

Alan Jay Cohen, MD, agreed with Dr. Jellinger. “Many patients have called the office in the last 10 days to ask if there are special precautions they should take because they are reading that they are in the high-risk group because they have diabetes. Many of them are in superb, or at least pretty good, control. I have not seen where they have had a higher incidence of infection than the general population, and I have not seen data with COVID-19 that specifically demonstrates that a person with diabetes in good control has an increased risk,” he said.

“My recommendations to these patients have been the same as those given to the general population,” added Dr. Cohen, medical director at Baptist Medical Group: The Endocrine Clinic, Memphis.

Herbert I. Rettinger, MD, also conceded that poorly controlled blood sugars and confounding illnesses, such as renal and cardiac conditions, are common in patients with long-standing diabetes, but “there is a huge population of patients with type 1 diabetes, and very few seem to be more susceptible to infection. Perhaps I am missing those with poor diet and glucose control.”

Philip Levy, MD, picked up on that latter point, emphasizing that “endocrinologists take care of fewer patients with diabetes than do primary care physicians. Most patients with type 2 diabetes are not seen by us unless the PCP has problems [treating them],” so it could be that PCPs may see a higher number of patients who are at a greater risk for infections.

Ultimately, “good glucose control is very helpful in avoiding infections,” said Dr. Levy, of the Banner University Medical Group Endocrinology & Diabetes, Phoenix.
 

For sick patients

Guidelines for patients at the Joslin Diabetes Center in Boston advise patients who are feeling sick to continue taking their diabetes medications, unless instructed otherwise by their providers, and to monitor their glucose more frequently because it can spike suddenly.

Patients with type 1 diabetes should check for ketones if their glucose passes 250 mg/dL, according to the guidelines, and patients should remain hydrated at all times and get plenty of rest.

“Sick-day guidelines definitely apply, but patients should be advised to get tested if they have any symptoms they are concerned about,” said Dr. Rettinger, of the Endocrinology Medical Group of Orange County, Orange, Calif.

If patients with diabetes develop COVID-19, then home management may still be possible, according to Ritesh Gupta, MD, of Fortis C-DOC Hospital, New Delhi, and colleagues (Diabetes Metab Syndr. 2020 Mar 10;14[3]:211-2. doi: 10.1016/j.dsx.2020.03.002).

Dr. Rettinger agreed, noting that home management would be feasible as long as “everything is going well, that is, the patient is not experiencing respiratory problems or difficulties in controlling glucose levels. Consider patients with type 1 diabetes who have COVID-19 as you would a nursing home patient – ever vigilant.”

Dr. Gupta and coauthors also recommended basic treatment measures such as maintaining hydration and managing symptoms with acetaminophen and steam inhalation, and home isolation for 14 days or until the symptoms resolve. However, the ADA warns in its guidelines that patients should “be aware that some constant glucose monitoring sensors (Dexcom G5, Medtronic Enlite, and Guardian) are impacted by acetaminophen (Tylenol), and that patients should check with finger sticks to ensure accuracy [if they are taking acetaminophen].”

In the event of hyperglycemia with fever in patients with type 1 diabetes, blood glucose and urinary ketones should be monitored often, the authors wrote, cautioning that “frequent changes in dosage and correctional bolus may be required to maintain normoglycemia.” Dr Rettinger emphasized that “hyperglycemia, as always, is best treated with fluids and insulin and frequent checks of sugars to be sure the treatment regimen is successful.”

In regard to diabetic drug regimens, patients with type 1 or 2 disease should continue on their current medications, advised Yehuda Handelsman, MD. “Some, especially those on insulin, may require more of it. And the patient should increase fluid intake to prevent fluid depletion. We do not reduce antihyperglycemic medication to preserve fluids.

Preventive measures

In the interest of maintaining good glucose control, patients also should monitor their glucose levels more frequently so that fluctuations can be detected early and quickly addressed with the appropriate medication adjustments, according to guidelines from the ADA and AACE. They should continue to follow a healthy diet that includes adequate protein and they should exercise regularly.

Patients should ensure that they have enough medication and testing supplies – for at least 14 days, and longer, if costs permit – in case they have to go into quarantine.

General preventive measures, such as frequent hand washing with soap and water, practicing good respiratory hygiene by sneezing or coughing into a facial tissue or bent elbow, also apply for reducing the risk of infection. Touching of the face should be avoided, as should nonessential travel and contact with infected individuals.

Patients with diabetes should always be current with their influenza and pneumonia shots.

Dr. Rettinger said that he always recommends the following preventative measures to his patients and he is using the current health crisis to reinforce them:

• Eat lots of multicolored fruits and vegetables.
• Eat yogurt and take probiotics to keep the intestinal biome strong and functional.
• Be extra vigilant regarding sugars and sugar control to avoid peaks and valleys wherever possible.
• Keep the immune system strong with at least 7-8 hours sleep and reduce stress levels whenever possible.
• Avoid crowds and handshaking.
• Wash hands regularly.

Possible therapies

There are currently no drugs that have been approved specifically for the treatment of COVID-19, although a vaccine against the disease is currently under development.

Dr. Gupta and his colleagues noted in their article that there have been reports of the anecdotal use of antiviral drugs such as lopinavir, ritonavir, interferon-beta, the RNA polymerase inhibitor remdesivir, and chloroquine.

However, Dr. Handelsman said that, as far as he knows, none of these drugs has been shown to be beneficial for COVID-19. “Some [providers] have tried Tamiflu, but with no clear outcomes, and for severely sick patients, they tried medications for anti-HIV, hepatitis C, and malaria, but so far, there has been no breakthrough.”

Dr. Cohen, Dr. Handelsman, Dr. Jellinger, Dr. Levy, and Dr. Rettinger are members of the editorial advisory board of Clinical Endocrinology News. Dr. Gupta and Dr. Wu, and their colleagues, reported no conflicts of interest.

[email protected]

Patients with diabetes may be at extra risk for coronavirus disease (COVID-19) mortality, and doctors treating them need to keep up with the latest guidelines and expert advice.

Most health advisories about COVID-19 mention diabetes as one of the high-risk categories for the disease, likely because early data coming out of China, where the disease was first reported, indicated an elevated case-fatality rate for COVID-19 patients who also had diabetes.

In an article published in JAMA, Zunyou Wu, MD, and Jennifer M. McGoogan, PhD, summarized the findings from a February report on 44,672 confirmed cases of the disease from the Chinese Center for Disease Control and Prevention. The overall case-fatality rate (CFR) at that stage was 2.3% (1,023 deaths of the 44,672 confirmed cases). The data indicated that the CFR was elevated among COVID-19 patients with preexisting comorbid conditions, specifically, cardiovascular disease (CFR, 10.5%), diabetes (7.3%), chronic respiratory disease (6.3%), hypertension (6%), and cancer (5.6%).

The data also showed an aged-related trend in the CFR, with patients aged 80 years or older having a CFR of 14.8% and those aged 70-79 years, a rate of 8.0%, while there were no fatal cases reported in patients aged 9 years or younger (JAMA. 2020 Feb 24. doi: 10.1001/jama.2020.2648).

Those findings have been echoed by the U.S. Centers of Disease Control and Prevention. The American Diabetes Association and the American Association of Clinical Endocrinologists have in turn referenced the CDC in their COVID-19 guidance recommendations for patients with diabetes.

Guidelines were already in place for treatment of infections in patients with diabetes, and at this stage, it seems that the same guidelines would extend to those patients who are also diagnosed with COVID-19, which is caused by the novel coronavirus, SARS-CoV-2.

In general, patients with diabetes – especially those whose disease is not controlled, or not well controlled – can be more susceptible to more common infections, such as influenza and pneumonia, possibly because hyperglycemia can subdue immunity by disrupting function of the white blood cells.
 

Glucose control is key

An important factor in any form of infection control in patients with diabetes seems to be whether or not a patient’s glucose levels are well controlled, according to comments from members of the editorial advisory board for Clinical Endocrinology News. Good glucose control, therefore, could be instrumental in reducing both the risk for and severity of infection.

Paul Jellinger, MD, of the Center for Diabetes & Endocrine Care, Hollywood, Fla., said that, over the years, he had not observed higher infection rates in general in patients with hemoglobin A_1c levels below 7, or even higher. However, “a bigger question for me, given the broad category of ‘diabetes’ listed as a risk for serious coronavirus complications by the CDC, has been: Just which individuals with diabetes are really at risk? Are patients with well-controlled diabetes at increased risk as much as those with significant hyperglycemia and uncontrolled diabetes? In my view, not likely.”

Alan Jay Cohen, MD, agreed with Dr. Jellinger. “Many patients have called the office in the last 10 days to ask if there are special precautions they should take because they are reading that they are in the high-risk group because they have diabetes. Many of them are in superb, or at least pretty good, control. I have not seen where they have had a higher incidence of infection than the general population, and I have not seen data with COVID-19 that specifically demonstrates that a person with diabetes in good control has an increased risk,” he said.

“My recommendations to these patients have been the same as those given to the general population,” added Dr. Cohen, medical director at Baptist Medical Group: The Endocrine Clinic, Memphis.

Herbert I. Rettinger, MD, also conceded that poorly controlled blood sugars and confounding illnesses, such as renal and cardiac conditions, are common in patients with long-standing diabetes, but “there is a huge population of patients with type 1 diabetes, and very few seem to be more susceptible to infection. Perhaps I am missing those with poor diet and glucose control.”

Philip Levy, MD, picked up on that latter point, emphasizing that “endocrinologists take care of fewer patients with diabetes than do primary care physicians. Most patients with type 2 diabetes are not seen by us unless the PCP has problems [treating them],” so it could be that PCPs may see a higher number of patients who are at a greater risk for infections.

Ultimately, “good glucose control is very helpful in avoiding infections,” said Dr. Levy, of the Banner University Medical Group Endocrinology & Diabetes, Phoenix.
 

For sick patients

Guidelines for patients at the Joslin Diabetes Center in Boston advise patients who are feeling sick to continue taking their diabetes medications, unless instructed otherwise by their providers, and to monitor their glucose more frequently because it can spike suddenly.

Patients with type 1 diabetes should check for ketones if their glucose passes 250 mg/dL, according to the guidelines, and patients should remain hydrated at all times and get plenty of rest.

“Sick-day guidelines definitely apply, but patients should be advised to get tested if they have any symptoms they are concerned about,” said Dr. Rettinger, of the Endocrinology Medical Group of Orange County, Orange, Calif.

If patients with diabetes develop COVID-19, then home management may still be possible, according to Ritesh Gupta, MD, of Fortis C-DOC Hospital, New Delhi, and colleagues (Diabetes Metab Syndr. 2020 Mar 10;14[3]:211-2. doi: 10.1016/j.dsx.2020.03.002).

Dr. Rettinger agreed, noting that home management would be feasible as long as “everything is going well, that is, the patient is not experiencing respiratory problems or difficulties in controlling glucose levels. Consider patients with type 1 diabetes who have COVID-19 as you would a nursing home patient – ever vigilant.”

Dr. Gupta and coauthors also recommended basic treatment measures such as maintaining hydration and managing symptoms with acetaminophen and steam inhalation, and home isolation for 14 days or until the symptoms resolve. However, the ADA warns in its guidelines that patients should “be aware that some constant glucose monitoring sensors (Dexcom G5, Medtronic Enlite, and Guardian) are impacted by acetaminophen (Tylenol), and that patients should check with finger sticks to ensure accuracy [if they are taking acetaminophen].”

In the event of hyperglycemia with fever in patients with type 1 diabetes, blood glucose and urinary ketones should be monitored often, the authors wrote, cautioning that “frequent changes in dosage and correctional bolus may be required to maintain normoglycemia.” Dr Rettinger emphasized that “hyperglycemia, as always, is best treated with fluids and insulin and frequent checks of sugars to be sure the treatment regimen is successful.”

In regard to diabetic drug regimens, patients with type 1 or 2 disease should continue on their current medications, advised Yehuda Handelsman, MD. “Some, especially those on insulin, may require more of it. And the patient should increase fluid intake to prevent fluid depletion. We do not reduce antihyperglycemic medication to preserve fluids.

Preventive measures

In the interest of maintaining good glucose control, patients also should monitor their glucose levels more frequently so that fluctuations can be detected early and quickly addressed with the appropriate medication adjustments, according to guidelines from the ADA and AACE. They should continue to follow a healthy diet that includes adequate protein and they should exercise regularly.

Patients should ensure that they have enough medication and testing supplies – for at least 14 days, and longer, if costs permit – in case they have to go into quarantine.

General preventive measures, such as frequent hand washing with soap and water, practicing good respiratory hygiene by sneezing or coughing into a facial tissue or bent elbow, also apply for reducing the risk of infection. Touching of the face should be avoided, as should nonessential travel and contact with infected individuals.

Patients with diabetes should always be current with their influenza and pneumonia shots.

Dr. Rettinger said that he always recommends the following preventative measures to his patients and he is using the current health crisis to reinforce them:

• Eat lots of multicolored fruits and vegetables.
• Eat yogurt and take probiotics to keep the intestinal biome strong and functional.
• Be extra vigilant regarding sugars and sugar control to avoid peaks and valleys wherever possible.
• Keep the immune system strong with at least 7-8 hours sleep and reduce stress levels whenever possible.
• Avoid crowds and handshaking.
• Wash hands regularly.

Possible therapies

There are currently no drugs that have been approved specifically for the treatment of COVID-19, although a vaccine against the disease is currently under development.

Dr. Gupta and his colleagues noted in their article that there have been reports of the anecdotal use of antiviral drugs such as lopinavir, ritonavir, interferon-beta, the RNA polymerase inhibitor remdesivir, and chloroquine.

However, Dr. Handelsman said that, as far as he knows, none of these drugs has been shown to be beneficial for COVID-19. “Some [providers] have tried Tamiflu, but with no clear outcomes, and for severely sick patients, they tried medications for anti-HIV, hepatitis C, and malaria, but so far, there has been no breakthrough.”

Dr. Cohen, Dr. Handelsman, Dr. Jellinger, Dr. Levy, and Dr. Rettinger are members of the editorial advisory board of Clinical Endocrinology News. Dr. Gupta and Dr. Wu, and their colleagues, reported no conflicts of interest.

[email protected]

Patients with diabetes may have an increased risk of developing coronavirus infection (COVID-19), along with increased risks of morbidity and mortality, according to researchers writing in Diabetes & Metabolic Syndrome.

Although relevant clinical data remain scarce, patients with diabetes should take extra precautions to avoid infection and, if infected, may require special care, reported Ritesh Gupta, MD, of Fortis C-DOC Hospital, New Delhi, and colleagues.

“The disease severity [with COVID-19] has varied from mild, self-limiting, flu-like illness to fulminant pneumonia, respiratory failure, and death,” the authors wrote.

As of March 16, 2020, the World Health Organization reported 167,515 confirmed cases of COVID-19 and 6,606 deaths from around the world, with a mortality rate of 3.9%. But the actual mortality rate may be lower, the authors suggested, because a study involving more than 1,000 confirmed cases reported a mortality rate of 1.4%.

“Considering that the number of unreported and unconfirmed cases is likely to be much higher than the reported cases, the actual mortality may be less than 1%, which is similar to that of severe seasonal influenza,” the authors said, in reference to an editorial by Anthony S. Fauci, MD, and colleagues in the New England Journal of Medicine. In addition, they noted, mortality rates may vary by region.

The largest study relevant to patients with diabetes, which involved 72,314 cases of COVID-19, showed that patients with diabetes had a threefold higher mortality rate than did those without diabetes (7.3% vs. 2.3%, respectively). These figures were reported by the Chinese Centre for Disease Control and Prevention.

However, data from smaller cohorts with diabetes and COVID-19 have yielded mixed results. For instance, one study, involving 140 patients from Wuhan, suggested that diabetes was not a risk factor for severe disease, and in an analysis of 11 studies reporting on laboratory abnormalities in patients with a diagnosis of COVID-19, raised blood sugar levels or diabetes were not mentioned among the predictors of severe disease.

“Our knowledge about the prevalence of COVID-19 and disease course in people with diabetes will evolve as more detailed analyses are carried out,” the authors wrote. “For now, it is reasonable to assume that people with diabetes are at increased risk of developing infection. Coexisting heart disease, kidney disease, advanced age, and frailty are likely to further increase the severity of disease.”
 

Prevention first

“It is important that people with diabetes maintain good glycemic control, because it might help in reducing the risk of infection and the severity,” the authors wrote.

In addition to more frequent monitoring of blood glucose levels, they recommended other preventive measures, such as getting adequate nutrition, exercising, and being current with vaccinations for influenza and pneumonia. The latter, they said, may also reduce the risk of secondary bacterial pneumonia after a respiratory viral infection.

In regard to nutrition, adequate protein intake is important and “any deficiencies of minerals and vitamins need to be taken care of,” they advised. Likewise, exercise is known to improve immunity and should continue, but they suggest avoiding gyms and swimming pools.

For patients with coexisting heart and/or kidney disease, they also recommended efforts to stabilize cardiac/renal status.

In addition, the general preventive measures, such as regular and thorough hand washing with soap and water, practicing good respiratory hygiene by sneezing and coughing into a bent elbow or a facial tissue, and avoiding contact with anyone who is infected, should be observed.

As with other patients with chronic diseases that are managed long-term medications, patients with diabetes should always ensure that they have a sufficient supply of their medications and refills, if possible.
 

After a diagnosis

If patients with diabetes develop COVID-19, then home management may still be possible, wrote the authors, who recommended basic treatment measures such as maintaining hydration and managing symptoms with acetaminophen and steam inhalation, and home isolation for 14 days or until the symptoms resolve.

In the event of hyperglycemia with fever in patients with type 1 diabetes, blood glucose and urinary ketones should be monitored often. “Frequent changes in dosage and correctional bolus may be required to maintain normoglycemia,” they cautioned.

Concerning diabetic drug regimens, they suggest patients avoid antihyperglycemic agents that can cause volume depletion or hypoglycemia and, if necessary, that they reduce oral antidiabetic drugs and follow sick-day guidelines.

For hospitalized patients, the investigators strengthened that statement, advising that oral agents need to be stopped, particularly sodium-glucose cotransporter 2 inhibitors and metformin. “Insulin is the preferred agent for control of hyperglycemia in hospitalized sick patients,” they wrote.

Untested therapies

The authors also discussed a range of untested therapies that may help fight COVID-19, such as antiviral drugs (such as lopinavir and ritonavir), zinc nanoparticles, and vitamin C. Supplementing those recommendations, Dr. Gupta and colleagues provided a concise review of COVID-19 epidemiology and extant data relevant to patients with diabetes.

The investigators reported no conflicts of interest.

SOURCE: Gupta et al. Diabetes Metab Syndr. 2020;14(3):211-12.

Patients with diabetes may have an increased risk of developing coronavirus infection (COVID-19), along with increased risks of morbidity and mortality, according to researchers writing in Diabetes & Metabolic Syndrome.

Although relevant clinical data remain scarce, patients with diabetes should take extra precautions to avoid infection and, if infected, may require special care, reported Ritesh Gupta, MD, of Fortis C-DOC Hospital, New Delhi, and colleagues.

“The disease severity [with COVID-19] has varied from mild, self-limiting, flu-like illness to fulminant pneumonia, respiratory failure, and death,” the authors wrote.

As of March 16, 2020, the World Health Organization reported 167,515 confirmed cases of COVID-19 and 6,606 deaths from around the world, with a mortality rate of 3.9%. But the actual mortality rate may be lower, the authors suggested, because a study involving more than 1,000 confirmed cases reported a mortality rate of 1.4%.

“Considering that the number of unreported and unconfirmed cases is likely to be much higher than the reported cases, the actual mortality may be less than 1%, which is similar to that of severe seasonal influenza,” the authors said, in reference to an editorial by Anthony S. Fauci, MD, and colleagues in the New England Journal of Medicine. In addition, they noted, mortality rates may vary by region.

The largest study relevant to patients with diabetes, which involved 72,314 cases of COVID-19, showed that patients with diabetes had a threefold higher mortality rate than did those without diabetes (7.3% vs. 2.3%, respectively). These figures were reported by the Chinese Centre for Disease Control and Prevention.

However, data from smaller cohorts with diabetes and COVID-19 have yielded mixed results. For instance, one study, involving 140 patients from Wuhan, suggested that diabetes was not a risk factor for severe disease, and in an analysis of 11 studies reporting on laboratory abnormalities in patients with a diagnosis of COVID-19, raised blood sugar levels or diabetes were not mentioned among the predictors of severe disease.

“Our knowledge about the prevalence of COVID-19 and disease course in people with diabetes will evolve as more detailed analyses are carried out,” the authors wrote. “For now, it is reasonable to assume that people with diabetes are at increased risk of developing infection. Coexisting heart disease, kidney disease, advanced age, and frailty are likely to further increase the severity of disease.”
 

Prevention first

“It is important that people with diabetes maintain good glycemic control, because it might help in reducing the risk of infection and the severity,” the authors wrote.

In addition to more frequent monitoring of blood glucose levels, they recommended other preventive measures, such as getting adequate nutrition, exercising, and being current with vaccinations for influenza and pneumonia. The latter, they said, may also reduce the risk of secondary bacterial pneumonia after a respiratory viral infection.

In regard to nutrition, adequate protein intake is important and “any deficiencies of minerals and vitamins need to be taken care of,” they advised. Likewise, exercise is known to improve immunity and should continue, but they suggest avoiding gyms and swimming pools.

For patients with coexisting heart and/or kidney disease, they also recommended efforts to stabilize cardiac/renal status.

In addition, the general preventive measures, such as regular and thorough hand washing with soap and water, practicing good respiratory hygiene by sneezing and coughing into a bent elbow or a facial tissue, and avoiding contact with anyone who is infected, should be observed.

As with other patients with chronic diseases that are managed long-term medications, patients with diabetes should always ensure that they have a sufficient supply of their medications and refills, if possible.
 

After a diagnosis

If patients with diabetes develop COVID-19, then home management may still be possible, wrote the authors, who recommended basic treatment measures such as maintaining hydration and managing symptoms with acetaminophen and steam inhalation, and home isolation for 14 days or until the symptoms resolve.

In the event of hyperglycemia with fever in patients with type 1 diabetes, blood glucose and urinary ketones should be monitored often. “Frequent changes in dosage and correctional bolus may be required to maintain normoglycemia,” they cautioned.

Concerning diabetic drug regimens, they suggest patients avoid antihyperglycemic agents that can cause volume depletion or hypoglycemia and, if necessary, that they reduce oral antidiabetic drugs and follow sick-day guidelines.

For hospitalized patients, the investigators strengthened that statement, advising that oral agents need to be stopped, particularly sodium-glucose cotransporter 2 inhibitors and metformin. “Insulin is the preferred agent for control of hyperglycemia in hospitalized sick patients,” they wrote.

Untested therapies

The authors also discussed a range of untested therapies that may help fight COVID-19, such as antiviral drugs (such as lopinavir and ritonavir), zinc nanoparticles, and vitamin C. Supplementing those recommendations, Dr. Gupta and colleagues provided a concise review of COVID-19 epidemiology and extant data relevant to patients with diabetes.

The investigators reported no conflicts of interest.

SOURCE: Gupta et al. Diabetes Metab Syndr. 2020;14(3):211-12.

Patients with diabetes may have an increased risk of developing coronavirus infection (COVID-19), along with increased risks of morbidity and mortality, according to researchers writing in Diabetes & Metabolic Syndrome.

Although relevant clinical data remain scarce, patients with diabetes should take extra precautions to avoid infection and, if infected, may require special care, reported Ritesh Gupta, MD, of Fortis C-DOC Hospital, New Delhi, and colleagues.

“The disease severity [with COVID-19] has varied from mild, self-limiting, flu-like illness to fulminant pneumonia, respiratory failure, and death,” the authors wrote.

As of March 16, 2020, the World Health Organization reported 167,515 confirmed cases of COVID-19 and 6,606 deaths from around the world, with a mortality rate of 3.9%. But the actual mortality rate may be lower, the authors suggested, because a study involving more than 1,000 confirmed cases reported a mortality rate of 1.4%.

“Considering that the number of unreported and unconfirmed cases is likely to be much higher than the reported cases, the actual mortality may be less than 1%, which is similar to that of severe seasonal influenza,” the authors said, in reference to an editorial by Anthony S. Fauci, MD, and colleagues in the New England Journal of Medicine. In addition, they noted, mortality rates may vary by region.

The largest study relevant to patients with diabetes, which involved 72,314 cases of COVID-19, showed that patients with diabetes had a threefold higher mortality rate than did those without diabetes (7.3% vs. 2.3%, respectively). These figures were reported by the Chinese Centre for Disease Control and Prevention.

However, data from smaller cohorts with diabetes and COVID-19 have yielded mixed results. For instance, one study, involving 140 patients from Wuhan, suggested that diabetes was not a risk factor for severe disease, and in an analysis of 11 studies reporting on laboratory abnormalities in patients with a diagnosis of COVID-19, raised blood sugar levels or diabetes were not mentioned among the predictors of severe disease.

“Our knowledge about the prevalence of COVID-19 and disease course in people with diabetes will evolve as more detailed analyses are carried out,” the authors wrote. “For now, it is reasonable to assume that people with diabetes are at increased risk of developing infection. Coexisting heart disease, kidney disease, advanced age, and frailty are likely to further increase the severity of disease.”
 

Prevention first

“It is important that people with diabetes maintain good glycemic control, because it might help in reducing the risk of infection and the severity,” the authors wrote.

In addition to more frequent monitoring of blood glucose levels, they recommended other preventive measures, such as getting adequate nutrition, exercising, and being current with vaccinations for influenza and pneumonia. The latter, they said, may also reduce the risk of secondary bacterial pneumonia after a respiratory viral infection.

In regard to nutrition, adequate protein intake is important and “any deficiencies of minerals and vitamins need to be taken care of,” they advised. Likewise, exercise is known to improve immunity and should continue, but they suggest avoiding gyms and swimming pools.

For patients with coexisting heart and/or kidney disease, they also recommended efforts to stabilize cardiac/renal status.

In addition, the general preventive measures, such as regular and thorough hand washing with soap and water, practicing good respiratory hygiene by sneezing and coughing into a bent elbow or a facial tissue, and avoiding contact with anyone who is infected, should be observed.

As with other patients with chronic diseases that are managed long-term medications, patients with diabetes should always ensure that they have a sufficient supply of their medications and refills, if possible.
 

After a diagnosis

If patients with diabetes develop COVID-19, then home management may still be possible, wrote the authors, who recommended basic treatment measures such as maintaining hydration and managing symptoms with acetaminophen and steam inhalation, and home isolation for 14 days or until the symptoms resolve.

In the event of hyperglycemia with fever in patients with type 1 diabetes, blood glucose and urinary ketones should be monitored often. “Frequent changes in dosage and correctional bolus may be required to maintain normoglycemia,” they cautioned.

Concerning diabetic drug regimens, they suggest patients avoid antihyperglycemic agents that can cause volume depletion or hypoglycemia and, if necessary, that they reduce oral antidiabetic drugs and follow sick-day guidelines.

For hospitalized patients, the investigators strengthened that statement, advising that oral agents need to be stopped, particularly sodium-glucose cotransporter 2 inhibitors and metformin. “Insulin is the preferred agent for control of hyperglycemia in hospitalized sick patients,” they wrote.

Untested therapies

The authors also discussed a range of untested therapies that may help fight COVID-19, such as antiviral drugs (such as lopinavir and ritonavir), zinc nanoparticles, and vitamin C. Supplementing those recommendations, Dr. Gupta and colleagues provided a concise review of COVID-19 epidemiology and extant data relevant to patients with diabetes.

The investigators reported no conflicts of interest.

SOURCE: Gupta et al. Diabetes Metab Syndr. 2020;14(3):211-12.

The Food and Drug Administration announced three measures aimed at improving the testing capacity for COVID-19.

Wikimedia Commons/FitzColinGerald/ Creative Commons License

First, the FDA is giving states more flexibility to approve and implement testing for COVID-19.

“States can set up a system in which they take responsibility for authorizing such tests and the laboratories will not engage with the FDA,” agency Commissioner Stephen Hahn, MD, said in a March 16 statement announcing the policy updates. “Laboratories developing tests in these states can engage directly with the appropriate state authorities, instead of with the FDA.”

A copy of the updated guidance document can be found here.

Dr. Hahn added that laboratories working within this authority granted to states will not have to pursue an emergency use authorization (EUA). New York state was previously granted a waiver to allow for more state oversight over the introduction of diagnostic testing.

Second, the FDA is expanding guidance issued on Feb. 29 on who can develop diagnostic tests. Originally, the Feb. 29 guidance was aimed at labs certified to perform high-complexity testing consistent with requirements outlined in the Clinical Laboratory Improvement Amendments.

“Under the update published today, the agency does not intend to object to commercial manufacturers distributing and labs using new commercially developed tests prior to the FDA granting an EUA, under certain circumstances,” Commissioner Hahn said, adding that a number of commercial manufacturers are developing tests for the coronavirus with the intent of submitting an EUA request.

“During this public health emergency, the FDA does not intend to object to the distribution and use of these tests for specimen testing for a reasonable period of time after the manufacturer’s validation of the test while the manufacturer is preparing its EUA request,” he added.

The updated guidance also provides recommendations for test developers working on serologic tests for COVID-19.

During a March 16 conference call with reporters, Commissioner Hahn said the flexibility would add a “significant number of tests and we believe this will be a surge to meet the demand that we expect to see, although it is somewhat difficult” to quantify the number of tests this new flexibility will bring to the market.

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The Food and Drug Administration announced three measures aimed at improving the testing capacity for COVID-19.

Wikimedia Commons/FitzColinGerald/ Creative Commons License

First, the FDA is giving states more flexibility to approve and implement testing for COVID-19.

“States can set up a system in which they take responsibility for authorizing such tests and the laboratories will not engage with the FDA,” agency Commissioner Stephen Hahn, MD, said in a March 16 statement announcing the policy updates. “Laboratories developing tests in these states can engage directly with the appropriate state authorities, instead of with the FDA.”

A copy of the updated guidance document can be found here.

Dr. Hahn added that laboratories working within this authority granted to states will not have to pursue an emergency use authorization (EUA). New York state was previously granted a waiver to allow for more state oversight over the introduction of diagnostic testing.

Second, the FDA is expanding guidance issued on Feb. 29 on who can develop diagnostic tests. Originally, the Feb. 29 guidance was aimed at labs certified to perform high-complexity testing consistent with requirements outlined in the Clinical Laboratory Improvement Amendments.

“Under the update published today, the agency does not intend to object to commercial manufacturers distributing and labs using new commercially developed tests prior to the FDA granting an EUA, under certain circumstances,” Commissioner Hahn said, adding that a number of commercial manufacturers are developing tests for the coronavirus with the intent of submitting an EUA request.

“During this public health emergency, the FDA does not intend to object to the distribution and use of these tests for specimen testing for a reasonable period of time after the manufacturer’s validation of the test while the manufacturer is preparing its EUA request,” he added.

The updated guidance also provides recommendations for test developers working on serologic tests for COVID-19.

During a March 16 conference call with reporters, Commissioner Hahn said the flexibility would add a “significant number of tests and we believe this will be a surge to meet the demand that we expect to see, although it is somewhat difficult” to quantify the number of tests this new flexibility will bring to the market.