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Graduates of international medical schools died from COVID-19 in disproportionate numbers in the United States in 2020, researchers report.

“I’ve always felt that international medical graduates [IMGs] in America are largely invisible,” said senior author Abraham Verghese, MD, MFA, an infectious disease specialist at Stanford (Calif.) University. “Everyone is aware that there are foreign doctors, but very few are aware of how many there are and also how vital they are to providing health care in America.”

IMGs made up 25% of all U.S. physicians in 2020 but accounted for 45% of those whose deaths had been attributed to COVID-19 through Nov. 23, 2020, Deendayal Dinakarpandian, MD, PhD, clinical associate professor of medicine at Stanford (Calif.) University, and colleagues report in JAMA Network Open.

IMGs are more likely to work in places where the incidence of COVID-19 is high and in facilities with fewer resources, Dr. Verghese said in an interview. “So, it’s not surprising that they were on the front lines when this thing came along,” he said.

To see whether their vulnerability affected their risk for death, Dr. Dinakarpandian and colleagues collected data from Nov. 23, 2020, from three sources of information regarding deaths among physicians: MedPage Today, which used investigative and voluntary reporting; Medscape, which used voluntary reporting of verifiable information; and a collaboration of The Guardian and Kaiser Health News, which used investigative reporting.

The Medscape project was launched on April 1, 2020. The MedPage Today and The Guardian/Kaiser Health News projects were launched on April 8, 2020.

Dr. Verghese and colleagues researched obituaries and news articles referenced by the three projects to verify their data. They used DocInfo to ascertain the deceased physicians’ medical schools.

After eliminating duplications from the lists, the researchers counted 132 physician deaths in 28 states. Of these, 59 physicians had graduated from medical schools outside the United States, a death toll 1.8 times higher than the proportion of IMGs among U.S. physicians (95% confidence interval, 1.52-2.21; P < .001).

New York, New Jersey, and Florida accounted for 66% of the deaths among IMGs but for only 45% of the deaths among U.S. medical school graduates.

Within each state, the proportion of IMGs among deceased physicians was not statistically different from their proportion among physicians in those states, with the exception of New York.

Two-thirds of the physicians’ deaths occurred in states where IMGs make up a larger proportion of physicians than in the nation as a whole. In these states, the incidence of COVID-19 was high at the start of the pandemic.

In New York, IMGs accounted for 60% of physician deaths, which was 1.62 times higher (95% CI, 1.26-2.09; P = .005) than the 37% among New York physicians overall.

Physicians who were trained abroad frequently can’t get into the most prestigious residency programs or into the highest paid specialties and are more likely to serve in primary care, Dr. Verghese said. Overall, 60% of the physicians who died of COVID-19 worked in primary care.

IMGs often staff hospitals serving low-income communities and communities of color, which were hardest hit by the pandemic and where personal protective equipment was hard to obtain, said Dr. Verghese.

In addition to these risks, IMGs sometimes endure racism, said Dr. Verghese, who obtained his medical degree at Madras Medical College, Chennai, India. “We’ve actually seen in the COVID era, in keeping with the sort of political tone that was set in Washington, that there’s been a lot more abuses of both foreign physicians and foreign looking physicians – even if they’re not foreign trained – and nurses by patients who have been given license. And I want to acknowledge the heroism of all these physicians.”

The study was partially funded by the Presence Center at Stanford. Dr. Verghese is a regular contributor to Medscape. He served on the advisory board for Gilead Sciences, serves as a speaker or a member of a speakers bureau for Leigh Bureau, and receives royalties from Penguin Random House and Simon & Schuster.

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

Graduates of international medical schools died from COVID-19 in disproportionate numbers in the United States in 2020, researchers report.

“I’ve always felt that international medical graduates [IMGs] in America are largely invisible,” said senior author Abraham Verghese, MD, MFA, an infectious disease specialist at Stanford (Calif.) University. “Everyone is aware that there are foreign doctors, but very few are aware of how many there are and also how vital they are to providing health care in America.”

IMGs made up 25% of all U.S. physicians in 2020 but accounted for 45% of those whose deaths had been attributed to COVID-19 through Nov. 23, 2020, Deendayal Dinakarpandian, MD, PhD, clinical associate professor of medicine at Stanford (Calif.) University, and colleagues report in JAMA Network Open.

IMGs are more likely to work in places where the incidence of COVID-19 is high and in facilities with fewer resources, Dr. Verghese said in an interview. “So, it’s not surprising that they were on the front lines when this thing came along,” he said.

To see whether their vulnerability affected their risk for death, Dr. Dinakarpandian and colleagues collected data from Nov. 23, 2020, from three sources of information regarding deaths among physicians: MedPage Today, which used investigative and voluntary reporting; Medscape, which used voluntary reporting of verifiable information; and a collaboration of The Guardian and Kaiser Health News, which used investigative reporting.

The Medscape project was launched on April 1, 2020. The MedPage Today and The Guardian/Kaiser Health News projects were launched on April 8, 2020.

Dr. Verghese and colleagues researched obituaries and news articles referenced by the three projects to verify their data. They used DocInfo to ascertain the deceased physicians’ medical schools.

After eliminating duplications from the lists, the researchers counted 132 physician deaths in 28 states. Of these, 59 physicians had graduated from medical schools outside the United States, a death toll 1.8 times higher than the proportion of IMGs among U.S. physicians (95% confidence interval, 1.52-2.21; P < .001).

New York, New Jersey, and Florida accounted for 66% of the deaths among IMGs but for only 45% of the deaths among U.S. medical school graduates.

Within each state, the proportion of IMGs among deceased physicians was not statistically different from their proportion among physicians in those states, with the exception of New York.

Two-thirds of the physicians’ deaths occurred in states where IMGs make up a larger proportion of physicians than in the nation as a whole. In these states, the incidence of COVID-19 was high at the start of the pandemic.

In New York, IMGs accounted for 60% of physician deaths, which was 1.62 times higher (95% CI, 1.26-2.09; P = .005) than the 37% among New York physicians overall.

Physicians who were trained abroad frequently can’t get into the most prestigious residency programs or into the highest paid specialties and are more likely to serve in primary care, Dr. Verghese said. Overall, 60% of the physicians who died of COVID-19 worked in primary care.

IMGs often staff hospitals serving low-income communities and communities of color, which were hardest hit by the pandemic and where personal protective equipment was hard to obtain, said Dr. Verghese.

In addition to these risks, IMGs sometimes endure racism, said Dr. Verghese, who obtained his medical degree at Madras Medical College, Chennai, India. “We’ve actually seen in the COVID era, in keeping with the sort of political tone that was set in Washington, that there’s been a lot more abuses of both foreign physicians and foreign looking physicians – even if they’re not foreign trained – and nurses by patients who have been given license. And I want to acknowledge the heroism of all these physicians.”

The study was partially funded by the Presence Center at Stanford. Dr. Verghese is a regular contributor to Medscape. He served on the advisory board for Gilead Sciences, serves as a speaker or a member of a speakers bureau for Leigh Bureau, and receives royalties from Penguin Random House and Simon & Schuster.

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

Graduates of international medical schools died from COVID-19 in disproportionate numbers in the United States in 2020, researchers report.

“I’ve always felt that international medical graduates [IMGs] in America are largely invisible,” said senior author Abraham Verghese, MD, MFA, an infectious disease specialist at Stanford (Calif.) University. “Everyone is aware that there are foreign doctors, but very few are aware of how many there are and also how vital they are to providing health care in America.”

IMGs made up 25% of all U.S. physicians in 2020 but accounted for 45% of those whose deaths had been attributed to COVID-19 through Nov. 23, 2020, Deendayal Dinakarpandian, MD, PhD, clinical associate professor of medicine at Stanford (Calif.) University, and colleagues report in JAMA Network Open.

IMGs are more likely to work in places where the incidence of COVID-19 is high and in facilities with fewer resources, Dr. Verghese said in an interview. “So, it’s not surprising that they were on the front lines when this thing came along,” he said.

To see whether their vulnerability affected their risk for death, Dr. Dinakarpandian and colleagues collected data from Nov. 23, 2020, from three sources of information regarding deaths among physicians: MedPage Today, which used investigative and voluntary reporting; Medscape, which used voluntary reporting of verifiable information; and a collaboration of The Guardian and Kaiser Health News, which used investigative reporting.

The Medscape project was launched on April 1, 2020. The MedPage Today and The Guardian/Kaiser Health News projects were launched on April 8, 2020.

Dr. Verghese and colleagues researched obituaries and news articles referenced by the three projects to verify their data. They used DocInfo to ascertain the deceased physicians’ medical schools.

After eliminating duplications from the lists, the researchers counted 132 physician deaths in 28 states. Of these, 59 physicians had graduated from medical schools outside the United States, a death toll 1.8 times higher than the proportion of IMGs among U.S. physicians (95% confidence interval, 1.52-2.21; P < .001).

New York, New Jersey, and Florida accounted for 66% of the deaths among IMGs but for only 45% of the deaths among U.S. medical school graduates.

Within each state, the proportion of IMGs among deceased physicians was not statistically different from their proportion among physicians in those states, with the exception of New York.

Two-thirds of the physicians’ deaths occurred in states where IMGs make up a larger proportion of physicians than in the nation as a whole. In these states, the incidence of COVID-19 was high at the start of the pandemic.

In New York, IMGs accounted for 60% of physician deaths, which was 1.62 times higher (95% CI, 1.26-2.09; P = .005) than the 37% among New York physicians overall.

Physicians who were trained abroad frequently can’t get into the most prestigious residency programs or into the highest paid specialties and are more likely to serve in primary care, Dr. Verghese said. Overall, 60% of the physicians who died of COVID-19 worked in primary care.

IMGs often staff hospitals serving low-income communities and communities of color, which were hardest hit by the pandemic and where personal protective equipment was hard to obtain, said Dr. Verghese.

In addition to these risks, IMGs sometimes endure racism, said Dr. Verghese, who obtained his medical degree at Madras Medical College, Chennai, India. “We’ve actually seen in the COVID era, in keeping with the sort of political tone that was set in Washington, that there’s been a lot more abuses of both foreign physicians and foreign looking physicians – even if they’re not foreign trained – and nurses by patients who have been given license. And I want to acknowledge the heroism of all these physicians.”

The study was partially funded by the Presence Center at Stanford. Dr. Verghese is a regular contributor to Medscape. He served on the advisory board for Gilead Sciences, serves as a speaker or a member of a speakers bureau for Leigh Bureau, and receives royalties from Penguin Random House and Simon & Schuster.

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

A new clinical score has been developed, and externally validated, to identify patients at risk of bleeding after transcatheter aortic valve replacement (TAVR).

“Despite the TAVR iterations, we recognize that bleeding remains a very important and perhaps also neglected issue. Indeed, no specifically developed standard algorithm existed before this to assess bleeding risk post-TAVR,” lead author Eliano Pio Navarese, MD, PhD, said in an interview.

Although bleeding rates can be as high as 9% at 30 days and between 3% and 11% in the first year, only a few studies have applied existing scores to TAVR patients, he noted.

The PREDICT-TAVR score includes six common variables and can be calculated by hand using a simple nomogram or a web-based calculator, with a dedicated website in the works, said Dr. Navarese, Nicolaus Copernicus University and SIRO MEDICINE Network, Bydgoszcz, Poland, and the University of Alberta, Edmonton.

A strength of the score is that machine-learning methods were used and the choice of variables optimized through recursive feature elimination and cross validation to remove the weakest variables, he said. Artificial intelligence, including use of random forest, naïve Bayes, and logistic regression classifiers, was also applied to the algorithms and the results cross-checked with standard multivariate analysis.

“It was a tremendous effort in terms of the analytics conducted,” Dr. Navarese said. “This is not a simple score but the integration of the most sophisticated machine learning methods and algorithms.”

Details are published in the June 14 issue of JACC: Cardiovascular Interventions.

The six variables used to calculate 30-day bleeding risk after TAVR and the points assigned to each are:

• blood hemoglobin (0-10 points)
• serum iron concentration (0-5 points)
• common femoral artery diameter (0-3 points)
•  (0-3 points)
• dual antiplatelet therapy (DAPT; 0-2 points)
• oral anticoagulation therapy (0-2 points)

The six items were selected among 104 baseline variables from 5,185 consecutive patients undergoing transfemoral TAVR in the prospective RISPEVA (Registro Italiano GISE sull’Impianto di Valvola Aortica Percutanea) registry between March 2012 and December 2019, then validated in 5,043 patients in the prospective POL-TAVI (Polish Registry of Transcatheter Aortic Valve Implantation) between January 2013 and December 2019.

In the derivation cohort, 216 patients (4.2%) experienced bleeding events at 1 year, with 169 events (78%) occurring during the first 30 days.

PREDICT-TAVR exhibited high discriminatory power for bleeding events at 30 days, as reflected by an area under the curve (AUC) of 0.80 (95% confidence interval, 0.75-0.83). Internal validation by optimism bootstrap-corrected AUC was consistent at 0.79 (95% CI, 0.75-0.83).

PREDICT-TAVR also outperformed scores not developed for TAVR, such as the PARIS score for patients undergoing percutaneous coronary intervention (AUC, 0.69) and the well-validated HAS-BLED for patients receiving anticoagulation (AUC, 0.58; P < .001 for both).

In the validation cohort, the AUC for bleeding complications at 30 days was 0.78 (95% CI, 0.72-0.82) versus an AUC of 0.68 for PARIS and 0.66 for HAS-BLED.

A HAS-BLED score of 4 predicted a higher rate of severe bleeding and mortality in the year after transfemoral TAVR in the 2018 Japanese OCEAN-TAVI study.
 

Bleeding events by risk categories

Risk score quartiles identified as low risk were 8 points or less, as moderate risk were 8 to less than 10 points, as high risk were 10 to less than 12 points, and as very-high-risk score were above 12 points.

In the derivation cohort, 30-day bleeding events across quartiles were 0.8%, 1.1%, 2.5%, and 8.5%, respectively (overall P < .001).

Compared with the lowest quartile, bleeding risk was numerically higher for the second quartile (odds ratio, 1.75) and significantly higher in the third (OR, 2.0) and fourth (OR, 2.49) quartiles (P < .001 for both).

A landmark cumulative-event analysis showed a significantly greater risk of bleeding for the two highest quartiles up to 30 days; however, these differences were no longer significant from 30 days to 1 year, likely because of a limited number of events, the authors suggest. Similar results were seen in the validation cohort.

The number of patients in the high- and very-high-risk groups isn’t trivial, and bleeding rates reached as high as 12.6% in the highest quartile, Dr. Navarese observed. Guidelines recommend DAPT for 3 to 6 months after TAVR; however, emerging data, including a recent meta-analysis, suggest monotherapy may be a very good option.

“So, if you had a high bleeding risk and are considering postprocedural DAPT or anticoagulation, I would think twice rather than administering dual antiplatelet therapy or anticoagulation for a long time, or at least, I would consider the impact of this score on this choice,” he said.

Subgroup analyses showed AUCs ranging from 0.77 to 0.81 for subgroups such as age older than 80 years, diabetes, obesity, female sex, previous PCI, and New York Heart Association class III or IV.

Serum iron showed the highest AUC in the primary PREDICT-TAVR model; however, should iron levels be unavailable, a simplified score modeled without iron levels retained predictive power, yielding AUCs for 30-day bleeding of 0.78 in the derivation cohort and 0.75 in the validation cohort.

“PREDICT-TAVR score can impact clinical practice, not only selecting the optimal thrombotic regimen in certain high bleeding-risk populations but also to treat pre-TAVR anemia and iron deficiencies, which may affect outcomes,” Dr. Navarese said. “Of course, future prospective biological and clinical investigations are needed to elucidate the score and the role of the score’s treatable risk traits in reducing post-TAVR bleeding complications.”

Commenting for this news organization, Sunil Rao, MD, Duke University, Durham, N.C., said anemia is a covariant in many risk models for bleeding and vascular complications in PCI and acute coronary syndrome, but hemoglobin and iron levels are collinear.

“The problem I think is when you throw hemoglobin and iron in the same model, just by play of chance, one variable can knock out the other one,” he said. “So I don’t know necessarily if we need to start measuring iron on everyone. We certainly should be measuring hemoglobin, which I think most people will have, and if a patient has pre-existing anemia, that should be a red flag for us.”

Age and Society of Thoracic Surgeons (STS) risk score did not reach statistical significance in the model – likely reflecting the high-/extremely-high-risk patient population with an average STS score of 7.7 and average age of 82 years – but may become more important as TAVR is applied more widely, Dr. Rao and Zachary Wegermann, MD, Duke Clinical Research Institute, write in an accompanying editorial.

They also point out that the study was limited by a low rate of bleeding events, and, importantly, the score can’t distinguish between minor or major bleeding.

“It’s worth trying to repeat the analyses in lower-risk patients because we may find other covariates that are important,” Dr. Rao said in an interview. “The other thing we need to get to is probably being a little bit more sophisticated. The variables included in these models are the ones that are measured; they’re also the ones that are clinically apparent.”

“But there’s a whole area of genomic medicine, proteomic medicine, metabolomic medicine that, as it starts developing and becomes more and more sophisticated, my suspicion is that we’re going to get even more precise and accurate about patients’ risk, and it’s going to become more individualized, rather than just measuring variables like age and lab values,” he said.

In the meantime, having variables documented in the electronic health record, with hard stops deployed if variables aren’t measured, is “a step in the right direction,” he added.

Dr. Navarese has received research grants from Abbott, Amgen, and Medtronic and received lecture fees and honoraria from Amgen, AstraZeneca, Bayer, Pfizer, and Sanofi-Regeneron, outside the submitted work. Dr. Rao and Dr. Wegermann report no relevant financial disclosures.

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

A new clinical score has been developed, and externally validated, to identify patients at risk of bleeding after transcatheter aortic valve replacement (TAVR).

“Despite the TAVR iterations, we recognize that bleeding remains a very important and perhaps also neglected issue. Indeed, no specifically developed standard algorithm existed before this to assess bleeding risk post-TAVR,” lead author Eliano Pio Navarese, MD, PhD, said in an interview.

Although bleeding rates can be as high as 9% at 30 days and between 3% and 11% in the first year, only a few studies have applied existing scores to TAVR patients, he noted.

The PREDICT-TAVR score includes six common variables and can be calculated by hand using a simple nomogram or a web-based calculator, with a dedicated website in the works, said Dr. Navarese, Nicolaus Copernicus University and SIRO MEDICINE Network, Bydgoszcz, Poland, and the University of Alberta, Edmonton.

A strength of the score is that machine-learning methods were used and the choice of variables optimized through recursive feature elimination and cross validation to remove the weakest variables, he said. Artificial intelligence, including use of random forest, naïve Bayes, and logistic regression classifiers, was also applied to the algorithms and the results cross-checked with standard multivariate analysis.

“It was a tremendous effort in terms of the analytics conducted,” Dr. Navarese said. “This is not a simple score but the integration of the most sophisticated machine learning methods and algorithms.”

Details are published in the June 14 issue of JACC: Cardiovascular Interventions.

The six variables used to calculate 30-day bleeding risk after TAVR and the points assigned to each are:

• blood hemoglobin (0-10 points)
• serum iron concentration (0-5 points)
• common femoral artery diameter (0-3 points)
•  (0-3 points)
• dual antiplatelet therapy (DAPT; 0-2 points)
• oral anticoagulation therapy (0-2 points)

The six items were selected among 104 baseline variables from 5,185 consecutive patients undergoing transfemoral TAVR in the prospective RISPEVA (Registro Italiano GISE sull’Impianto di Valvola Aortica Percutanea) registry between March 2012 and December 2019, then validated in 5,043 patients in the prospective POL-TAVI (Polish Registry of Transcatheter Aortic Valve Implantation) between January 2013 and December 2019.

In the derivation cohort, 216 patients (4.2%) experienced bleeding events at 1 year, with 169 events (78%) occurring during the first 30 days.

PREDICT-TAVR exhibited high discriminatory power for bleeding events at 30 days, as reflected by an area under the curve (AUC) of 0.80 (95% confidence interval, 0.75-0.83). Internal validation by optimism bootstrap-corrected AUC was consistent at 0.79 (95% CI, 0.75-0.83).

PREDICT-TAVR also outperformed scores not developed for TAVR, such as the PARIS score for patients undergoing percutaneous coronary intervention (AUC, 0.69) and the well-validated HAS-BLED for patients receiving anticoagulation (AUC, 0.58; P < .001 for both).

In the validation cohort, the AUC for bleeding complications at 30 days was 0.78 (95% CI, 0.72-0.82) versus an AUC of 0.68 for PARIS and 0.66 for HAS-BLED.

A HAS-BLED score of 4 predicted a higher rate of severe bleeding and mortality in the year after transfemoral TAVR in the 2018 Japanese OCEAN-TAVI study.
 

Bleeding events by risk categories

Risk score quartiles identified as low risk were 8 points or less, as moderate risk were 8 to less than 10 points, as high risk were 10 to less than 12 points, and as very-high-risk score were above 12 points.

In the derivation cohort, 30-day bleeding events across quartiles were 0.8%, 1.1%, 2.5%, and 8.5%, respectively (overall P < .001).

Compared with the lowest quartile, bleeding risk was numerically higher for the second quartile (odds ratio, 1.75) and significantly higher in the third (OR, 2.0) and fourth (OR, 2.49) quartiles (P < .001 for both).

A landmark cumulative-event analysis showed a significantly greater risk of bleeding for the two highest quartiles up to 30 days; however, these differences were no longer significant from 30 days to 1 year, likely because of a limited number of events, the authors suggest. Similar results were seen in the validation cohort.

The number of patients in the high- and very-high-risk groups isn’t trivial, and bleeding rates reached as high as 12.6% in the highest quartile, Dr. Navarese observed. Guidelines recommend DAPT for 3 to 6 months after TAVR; however, emerging data, including a recent meta-analysis, suggest monotherapy may be a very good option.

“So, if you had a high bleeding risk and are considering postprocedural DAPT or anticoagulation, I would think twice rather than administering dual antiplatelet therapy or anticoagulation for a long time, or at least, I would consider the impact of this score on this choice,” he said.

Subgroup analyses showed AUCs ranging from 0.77 to 0.81 for subgroups such as age older than 80 years, diabetes, obesity, female sex, previous PCI, and New York Heart Association class III or IV.

Serum iron showed the highest AUC in the primary PREDICT-TAVR model; however, should iron levels be unavailable, a simplified score modeled without iron levels retained predictive power, yielding AUCs for 30-day bleeding of 0.78 in the derivation cohort and 0.75 in the validation cohort.

“PREDICT-TAVR score can impact clinical practice, not only selecting the optimal thrombotic regimen in certain high bleeding-risk populations but also to treat pre-TAVR anemia and iron deficiencies, which may affect outcomes,” Dr. Navarese said. “Of course, future prospective biological and clinical investigations are needed to elucidate the score and the role of the score’s treatable risk traits in reducing post-TAVR bleeding complications.”

Commenting for this news organization, Sunil Rao, MD, Duke University, Durham, N.C., said anemia is a covariant in many risk models for bleeding and vascular complications in PCI and acute coronary syndrome, but hemoglobin and iron levels are collinear.

“The problem I think is when you throw hemoglobin and iron in the same model, just by play of chance, one variable can knock out the other one,” he said. “So I don’t know necessarily if we need to start measuring iron on everyone. We certainly should be measuring hemoglobin, which I think most people will have, and if a patient has pre-existing anemia, that should be a red flag for us.”

Age and Society of Thoracic Surgeons (STS) risk score did not reach statistical significance in the model – likely reflecting the high-/extremely-high-risk patient population with an average STS score of 7.7 and average age of 82 years – but may become more important as TAVR is applied more widely, Dr. Rao and Zachary Wegermann, MD, Duke Clinical Research Institute, write in an accompanying editorial.

They also point out that the study was limited by a low rate of bleeding events, and, importantly, the score can’t distinguish between minor or major bleeding.

“It’s worth trying to repeat the analyses in lower-risk patients because we may find other covariates that are important,” Dr. Rao said in an interview. “The other thing we need to get to is probably being a little bit more sophisticated. The variables included in these models are the ones that are measured; they’re also the ones that are clinically apparent.”

“But there’s a whole area of genomic medicine, proteomic medicine, metabolomic medicine that, as it starts developing and becomes more and more sophisticated, my suspicion is that we’re going to get even more precise and accurate about patients’ risk, and it’s going to become more individualized, rather than just measuring variables like age and lab values,” he said.

In the meantime, having variables documented in the electronic health record, with hard stops deployed if variables aren’t measured, is “a step in the right direction,” he added.

Dr. Navarese has received research grants from Abbott, Amgen, and Medtronic and received lecture fees and honoraria from Amgen, AstraZeneca, Bayer, Pfizer, and Sanofi-Regeneron, outside the submitted work. Dr. Rao and Dr. Wegermann report no relevant financial disclosures.

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

A new clinical score has been developed, and externally validated, to identify patients at risk of bleeding after transcatheter aortic valve replacement (TAVR).

“Despite the TAVR iterations, we recognize that bleeding remains a very important and perhaps also neglected issue. Indeed, no specifically developed standard algorithm existed before this to assess bleeding risk post-TAVR,” lead author Eliano Pio Navarese, MD, PhD, said in an interview.

Although bleeding rates can be as high as 9% at 30 days and between 3% and 11% in the first year, only a few studies have applied existing scores to TAVR patients, he noted.

The PREDICT-TAVR score includes six common variables and can be calculated by hand using a simple nomogram or a web-based calculator, with a dedicated website in the works, said Dr. Navarese, Nicolaus Copernicus University and SIRO MEDICINE Network, Bydgoszcz, Poland, and the University of Alberta, Edmonton.

A strength of the score is that machine-learning methods were used and the choice of variables optimized through recursive feature elimination and cross validation to remove the weakest variables, he said. Artificial intelligence, including use of random forest, naïve Bayes, and logistic regression classifiers, was also applied to the algorithms and the results cross-checked with standard multivariate analysis.

“It was a tremendous effort in terms of the analytics conducted,” Dr. Navarese said. “This is not a simple score but the integration of the most sophisticated machine learning methods and algorithms.”

Details are published in the June 14 issue of JACC: Cardiovascular Interventions.

The six variables used to calculate 30-day bleeding risk after TAVR and the points assigned to each are:

• blood hemoglobin (0-10 points)
• serum iron concentration (0-5 points)
• common femoral artery diameter (0-3 points)
•  (0-3 points)
• dual antiplatelet therapy (DAPT; 0-2 points)
• oral anticoagulation therapy (0-2 points)

The six items were selected among 104 baseline variables from 5,185 consecutive patients undergoing transfemoral TAVR in the prospective RISPEVA (Registro Italiano GISE sull’Impianto di Valvola Aortica Percutanea) registry between March 2012 and December 2019, then validated in 5,043 patients in the prospective POL-TAVI (Polish Registry of Transcatheter Aortic Valve Implantation) between January 2013 and December 2019.

In the derivation cohort, 216 patients (4.2%) experienced bleeding events at 1 year, with 169 events (78%) occurring during the first 30 days.

PREDICT-TAVR exhibited high discriminatory power for bleeding events at 30 days, as reflected by an area under the curve (AUC) of 0.80 (95% confidence interval, 0.75-0.83). Internal validation by optimism bootstrap-corrected AUC was consistent at 0.79 (95% CI, 0.75-0.83).

PREDICT-TAVR also outperformed scores not developed for TAVR, such as the PARIS score for patients undergoing percutaneous coronary intervention (AUC, 0.69) and the well-validated HAS-BLED for patients receiving anticoagulation (AUC, 0.58; P < .001 for both).

In the validation cohort, the AUC for bleeding complications at 30 days was 0.78 (95% CI, 0.72-0.82) versus an AUC of 0.68 for PARIS and 0.66 for HAS-BLED.

A HAS-BLED score of 4 predicted a higher rate of severe bleeding and mortality in the year after transfemoral TAVR in the 2018 Japanese OCEAN-TAVI study.
 

Bleeding events by risk categories

Risk score quartiles identified as low risk were 8 points or less, as moderate risk were 8 to less than 10 points, as high risk were 10 to less than 12 points, and as very-high-risk score were above 12 points.

In the derivation cohort, 30-day bleeding events across quartiles were 0.8%, 1.1%, 2.5%, and 8.5%, respectively (overall P < .001).

Compared with the lowest quartile, bleeding risk was numerically higher for the second quartile (odds ratio, 1.75) and significantly higher in the third (OR, 2.0) and fourth (OR, 2.49) quartiles (P < .001 for both).

A landmark cumulative-event analysis showed a significantly greater risk of bleeding for the two highest quartiles up to 30 days; however, these differences were no longer significant from 30 days to 1 year, likely because of a limited number of events, the authors suggest. Similar results were seen in the validation cohort.

The number of patients in the high- and very-high-risk groups isn’t trivial, and bleeding rates reached as high as 12.6% in the highest quartile, Dr. Navarese observed. Guidelines recommend DAPT for 3 to 6 months after TAVR; however, emerging data, including a recent meta-analysis, suggest monotherapy may be a very good option.

“So, if you had a high bleeding risk and are considering postprocedural DAPT or anticoagulation, I would think twice rather than administering dual antiplatelet therapy or anticoagulation for a long time, or at least, I would consider the impact of this score on this choice,” he said.

Subgroup analyses showed AUCs ranging from 0.77 to 0.81 for subgroups such as age older than 80 years, diabetes, obesity, female sex, previous PCI, and New York Heart Association class III or IV.

Serum iron showed the highest AUC in the primary PREDICT-TAVR model; however, should iron levels be unavailable, a simplified score modeled without iron levels retained predictive power, yielding AUCs for 30-day bleeding of 0.78 in the derivation cohort and 0.75 in the validation cohort.

“PREDICT-TAVR score can impact clinical practice, not only selecting the optimal thrombotic regimen in certain high bleeding-risk populations but also to treat pre-TAVR anemia and iron deficiencies, which may affect outcomes,” Dr. Navarese said. “Of course, future prospective biological and clinical investigations are needed to elucidate the score and the role of the score’s treatable risk traits in reducing post-TAVR bleeding complications.”

Commenting for this news organization, Sunil Rao, MD, Duke University, Durham, N.C., said anemia is a covariant in many risk models for bleeding and vascular complications in PCI and acute coronary syndrome, but hemoglobin and iron levels are collinear.

“The problem I think is when you throw hemoglobin and iron in the same model, just by play of chance, one variable can knock out the other one,” he said. “So I don’t know necessarily if we need to start measuring iron on everyone. We certainly should be measuring hemoglobin, which I think most people will have, and if a patient has pre-existing anemia, that should be a red flag for us.”

Age and Society of Thoracic Surgeons (STS) risk score did not reach statistical significance in the model – likely reflecting the high-/extremely-high-risk patient population with an average STS score of 7.7 and average age of 82 years – but may become more important as TAVR is applied more widely, Dr. Rao and Zachary Wegermann, MD, Duke Clinical Research Institute, write in an accompanying editorial.

They also point out that the study was limited by a low rate of bleeding events, and, importantly, the score can’t distinguish between minor or major bleeding.

“It’s worth trying to repeat the analyses in lower-risk patients because we may find other covariates that are important,” Dr. Rao said in an interview. “The other thing we need to get to is probably being a little bit more sophisticated. The variables included in these models are the ones that are measured; they’re also the ones that are clinically apparent.”

“But there’s a whole area of genomic medicine, proteomic medicine, metabolomic medicine that, as it starts developing and becomes more and more sophisticated, my suspicion is that we’re going to get even more precise and accurate about patients’ risk, and it’s going to become more individualized, rather than just measuring variables like age and lab values,” he said.

In the meantime, having variables documented in the electronic health record, with hard stops deployed if variables aren’t measured, is “a step in the right direction,” he added.

Dr. Navarese has received research grants from Abbott, Amgen, and Medtronic and received lecture fees and honoraria from Amgen, AstraZeneca, Bayer, Pfizer, and Sanofi-Regeneron, outside the submitted work. Dr. Rao and Dr. Wegermann report no relevant financial disclosures.

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

Background: Critically ill patients are often vitamin D deficient, but no large randomized trials have investigated whether early vitamin D supplementation can affect clinical outcomes.

Study design: Multicenter, randomized, double-blind, placebo-controlled phase 3 trial.Setting: 44 U.S. hospitals, during April 2017–July 2018.

Synopsis: The study enrolled 1,078 patients with 25-hydroxyvitamin D levels < 20 ng/mL who were critically ill (defined as patients being admitted to the ICU with one or more risk factor for lung injury or death). Participants were randomized to early administration of a single dose of 540,000 IUs of enteral vitamin D₃ or placebo. The authors did not identify a statistically significant difference in the 90-day all-cause mortality between the two groups. Additionally, there were no significant differences in length of stay, ventilator-free days or serious adverse outcomes between the two groups.

Bottom line: Early administration of high-dose enteral vitamin D₃ did not decrease 90-day all-cause mortality in critically ill, vitamin D–deficient patients.

Citation: Ginde A et al. Early high-dose vitamin D₃ for critically ill, vitamin D–deficient patients. N Engl J Med. 2019 Dec 26; 281:2529-40.

Dr. Persaud is a hospitalist, Beth Israel Deaconess Medical Center, and instructor in medicine, Harvard Medical School, both in Boston.

Background: Critically ill patients are often vitamin D deficient, but no large randomized trials have investigated whether early vitamin D supplementation can affect clinical outcomes.

Study design: Multicenter, randomized, double-blind, placebo-controlled phase 3 trial.Setting: 44 U.S. hospitals, during April 2017–July 2018.

Synopsis: The study enrolled 1,078 patients with 25-hydroxyvitamin D levels < 20 ng/mL who were critically ill (defined as patients being admitted to the ICU with one or more risk factor for lung injury or death). Participants were randomized to early administration of a single dose of 540,000 IUs of enteral vitamin D₃ or placebo. The authors did not identify a statistically significant difference in the 90-day all-cause mortality between the two groups. Additionally, there were no significant differences in length of stay, ventilator-free days or serious adverse outcomes between the two groups.

Bottom line: Early administration of high-dose enteral vitamin D₃ did not decrease 90-day all-cause mortality in critically ill, vitamin D–deficient patients.

Citation: Ginde A et al. Early high-dose vitamin D₃ for critically ill, vitamin D–deficient patients. N Engl J Med. 2019 Dec 26; 281:2529-40.

Dr. Persaud is a hospitalist, Beth Israel Deaconess Medical Center, and instructor in medicine, Harvard Medical School, both in Boston.

Background: Critically ill patients are often vitamin D deficient, but no large randomized trials have investigated whether early vitamin D supplementation can affect clinical outcomes.

Study design: Multicenter, randomized, double-blind, placebo-controlled phase 3 trial.Setting: 44 U.S. hospitals, during April 2017–July 2018.

Synopsis: The study enrolled 1,078 patients with 25-hydroxyvitamin D levels < 20 ng/mL who were critically ill (defined as patients being admitted to the ICU with one or more risk factor for lung injury or death). Participants were randomized to early administration of a single dose of 540,000 IUs of enteral vitamin D₃ or placebo. The authors did not identify a statistically significant difference in the 90-day all-cause mortality between the two groups. Additionally, there were no significant differences in length of stay, ventilator-free days or serious adverse outcomes between the two groups.

Bottom line: Early administration of high-dose enteral vitamin D₃ did not decrease 90-day all-cause mortality in critically ill, vitamin D–deficient patients.

Citation: Ginde A et al. Early high-dose vitamin D₃ for critically ill, vitamin D–deficient patients. N Engl J Med. 2019 Dec 26; 281:2529-40.

Dr. Persaud is a hospitalist, Beth Israel Deaconess Medical Center, and instructor in medicine, Harvard Medical School, both in Boston.

Inhibiting granulocyte/macrophage–colony stimulating factor (GM-CSF) with mavrilimumab prevented some patients with severe COVID-19 pneumonia and hyperinflammation from needing mechanical ventilation and reduced their risk of dying versus placebo in a phase 2 study.

There was no difference in outcomes between the two doses of mavrilimumab used in the trial (6 mg/kg or 10 mg/kg) and combined data showed a higher percentage of patients achieving the primary endpoint of being alive and free of mechanical ventilation at 29 days, at 87%, versus placebo, at 74%.

The P value was 0.12, “which achieved the prespecified evidentiary standard of 0.2,” according to Lara Pupim, MD, vice president of clinical research and development at Kiniksa Pharmaceuticals in Lexington, Mass.

Importantly, there was a 61% reduction in the risk of dying if patients had received mavrilimumab rather than placebo, she reported at the annual European Congress of Rheumatology. Mortality at day 29 was 21% in the placebo arm but just 8% in the combined mavrilimumab arms (P = .07).

Hendrik Schulze-Koops, MD, called it a “surprising study” and that “the outcome is very spectacular” in his short appraisal of the study during the Clinical Highlights session on the final day of the congress.

Mavrilimumab was “a compound that we would not have thought that would have such an impact on the outcome of COVID-19 infected patients,” Dr. Schulze-Koops of Ludwig Maximilian University of Munich added.

In this small study, “there was a consistent suggestion of a biological effect across key endpoints,” Richard Conway, MBChB, PhD, a consultant rheumatologist at St. James’s Hospital in Dublin, pointed out in an interview.

“Similar to tocilizumab, the benefits with mavrilimumab appear to be in addition to those seen with glucocorticoids, as 96% of patients received dexamethasone,” Dr. Conway observed. Furthermore, nearly one-third received antiviral or remdesivir treatment.

“This study was likely underpowered to assess a clinically meaningful benefit,” he said, adding that “there is insufficient evidence at present to begin using mavrilimumab as an alternative to currently available agents.” That said, “these results are promising for future studies.”

Rationale for GM-CSF inhibition with mavrilimumab in COVID-19 pneumonia

“The cytokine GM-CSF is vital to both lung homeostasis and regulation of inflammation in autoimmunity,” Dr. Pupim explained.

She added that “GM-CSF is implicated in the mechanism of aberrant immune cell infiltration and activation in the lungs, and it may contribute to respiratory failure and death in patients with severe COVID-19 pneumonia and systemic hyperinflammation.”

The efficacy and safety of blocking GM-CSF with mavrilimumab have been shown previously in phase 2 studies in other diseases, Dr. Pupim noted. This includes patients with rheumatoid arthritis and those with giant cell arteritis.

“It was hypothesized that GM-CSF receptor–alpha blockade may reduce infiltration of pathogenic cells into the lung and may suppress inflammation in COVID-19 pneumonia in hyperinflammation,” she explained.

Study details and other outcome results

The study presented by Dr. Pupim was a phase 2/3 double-blind, placebo-controlled trial predominantly conducted in Brazil, the United States, and South Africa, with some participation in Peru and Chile.

Patients were eligible for inclusion if they had had a positive COVID-19 test within 14 days of randomization and had been hospitalized but not ventilated. Evidence of bilateral pneumonia on chest x-ray or CT scan and clinical laboratory evidence indicative of hyperinflammation were also prerequisites for study enrollment.

The ongoing study comprised two cohorts, Dr. Pupim explained: patients who have not been ventilated and those who have recently been ventilated. Dr. Pupim presented the data on the nonventilated cohort, noting that there was a total of 116 patients aged a mean of 57 years.

Patients were randomized to one of three treatment arms: two groups received a single intravenous infusion of mavrilimumab, either 6 mg/kg or 10 mg/kg, and the third group got a placebo.

“Using a time-to-event approach, looking at mechanical ventilation-free survival, mavrilimumab recipients experienced a 65% reduction in the risk of mechanical ventilation or death,” Dr. Pupim said (P = .0175).

“Separation in the Kaplan-Meier curves was evident very early after study drug administration,” she added.

There were trends toward a faster benefit with mavrilimumab than placebo in two other key secondary endpoints: the median time to achieving a two-point clinical improvement (7 vs. 11 days) and the median time to room air (7 vs. 9 days).

Timing of mavrilimumab administration and safety

Study coauthor and chief clinical development officer at Kiniksa, Arian Pano, MD, answered questions on the presentation. When asked about the timing of giving mavrilimumab, he said: “Based on these data it is before they go to ventilation, as soon as you have symptoms of hyperinflammation and a need for oxygen.”

Mavrilimumab is given as a single infusion “and has been well tolerated; virtually no interruptions occurred in this study.”

No serious adverse events related to mavrilimumab were seen, and adverse events, including secondary infections, which are known complications of COVID-19, occurred less frequently in mavrilimumab recipients, compared with placebo.

Dr. Pupim reported that there was a case of tuberculosis in one patient treated with mavrilimumab (10 mg/kg). That case had occurred in an “endemic area for tuberculosis,” and the patient had been screened before entry but only via a sputum sample.

“Prior to these events, the patient received high-dose corticosteroids, a known risk factor for reactivation of TB, and thus the potential additive contribution of mavrilimumab, if any, is uncertain.” Dr. Pupim said.

“Thrombotic events, another known complication of COVID-19, occurred in the placebo arm only,” she added.

Dr. Pano commented that the study has now “seamlessly continued to phase 3. So, basically, we did not stop the study. At the end of phase 2, we just locked the database and collected the data.” Both the 6 mg/kg and 10 mg/kg are being studied, but it’s “very likely [that] 6 mg/kg could be the dose that we may bring forward to the clinic in terms of registration, but that’s at this point in time. We will need to wait for the phase 3 data,” he observed. Those findings will hopefully be available later this year.

Kiniksa funded the study. Dr. Pupim, Dr. Pano, and multiple study coinvestigators are employees of the company.

Dr. Schulze-Koops was not involved in the study and had no specific disclosures. Dr. Conway had no financial disclosures to make in relation to his comments.

Inhibiting granulocyte/macrophage–colony stimulating factor (GM-CSF) with mavrilimumab prevented some patients with severe COVID-19 pneumonia and hyperinflammation from needing mechanical ventilation and reduced their risk of dying versus placebo in a phase 2 study.

There was no difference in outcomes between the two doses of mavrilimumab used in the trial (6 mg/kg or 10 mg/kg) and combined data showed a higher percentage of patients achieving the primary endpoint of being alive and free of mechanical ventilation at 29 days, at 87%, versus placebo, at 74%.

The P value was 0.12, “which achieved the prespecified evidentiary standard of 0.2,” according to Lara Pupim, MD, vice president of clinical research and development at Kiniksa Pharmaceuticals in Lexington, Mass.

Importantly, there was a 61% reduction in the risk of dying if patients had received mavrilimumab rather than placebo, she reported at the annual European Congress of Rheumatology. Mortality at day 29 was 21% in the placebo arm but just 8% in the combined mavrilimumab arms (P = .07).

Hendrik Schulze-Koops, MD, called it a “surprising study” and that “the outcome is very spectacular” in his short appraisal of the study during the Clinical Highlights session on the final day of the congress.

Mavrilimumab was “a compound that we would not have thought that would have such an impact on the outcome of COVID-19 infected patients,” Dr. Schulze-Koops of Ludwig Maximilian University of Munich added.

In this small study, “there was a consistent suggestion of a biological effect across key endpoints,” Richard Conway, MBChB, PhD, a consultant rheumatologist at St. James’s Hospital in Dublin, pointed out in an interview.

“Similar to tocilizumab, the benefits with mavrilimumab appear to be in addition to those seen with glucocorticoids, as 96% of patients received dexamethasone,” Dr. Conway observed. Furthermore, nearly one-third received antiviral or remdesivir treatment.

“This study was likely underpowered to assess a clinically meaningful benefit,” he said, adding that “there is insufficient evidence at present to begin using mavrilimumab as an alternative to currently available agents.” That said, “these results are promising for future studies.”

Rationale for GM-CSF inhibition with mavrilimumab in COVID-19 pneumonia

“The cytokine GM-CSF is vital to both lung homeostasis and regulation of inflammation in autoimmunity,” Dr. Pupim explained.

She added that “GM-CSF is implicated in the mechanism of aberrant immune cell infiltration and activation in the lungs, and it may contribute to respiratory failure and death in patients with severe COVID-19 pneumonia and systemic hyperinflammation.”

The efficacy and safety of blocking GM-CSF with mavrilimumab have been shown previously in phase 2 studies in other diseases, Dr. Pupim noted. This includes patients with rheumatoid arthritis and those with giant cell arteritis.

“It was hypothesized that GM-CSF receptor–alpha blockade may reduce infiltration of pathogenic cells into the lung and may suppress inflammation in COVID-19 pneumonia in hyperinflammation,” she explained.

Study details and other outcome results

The study presented by Dr. Pupim was a phase 2/3 double-blind, placebo-controlled trial predominantly conducted in Brazil, the United States, and South Africa, with some participation in Peru and Chile.

Patients were eligible for inclusion if they had had a positive COVID-19 test within 14 days of randomization and had been hospitalized but not ventilated. Evidence of bilateral pneumonia on chest x-ray or CT scan and clinical laboratory evidence indicative of hyperinflammation were also prerequisites for study enrollment.

The ongoing study comprised two cohorts, Dr. Pupim explained: patients who have not been ventilated and those who have recently been ventilated. Dr. Pupim presented the data on the nonventilated cohort, noting that there was a total of 116 patients aged a mean of 57 years.

Patients were randomized to one of three treatment arms: two groups received a single intravenous infusion of mavrilimumab, either 6 mg/kg or 10 mg/kg, and the third group got a placebo.

“Using a time-to-event approach, looking at mechanical ventilation-free survival, mavrilimumab recipients experienced a 65% reduction in the risk of mechanical ventilation or death,” Dr. Pupim said (P = .0175).

“Separation in the Kaplan-Meier curves was evident very early after study drug administration,” she added.

There were trends toward a faster benefit with mavrilimumab than placebo in two other key secondary endpoints: the median time to achieving a two-point clinical improvement (7 vs. 11 days) and the median time to room air (7 vs. 9 days).

Timing of mavrilimumab administration and safety

Study coauthor and chief clinical development officer at Kiniksa, Arian Pano, MD, answered questions on the presentation. When asked about the timing of giving mavrilimumab, he said: “Based on these data it is before they go to ventilation, as soon as you have symptoms of hyperinflammation and a need for oxygen.”

Mavrilimumab is given as a single infusion “and has been well tolerated; virtually no interruptions occurred in this study.”

No serious adverse events related to mavrilimumab were seen, and adverse events, including secondary infections, which are known complications of COVID-19, occurred less frequently in mavrilimumab recipients, compared with placebo.

Dr. Pupim reported that there was a case of tuberculosis in one patient treated with mavrilimumab (10 mg/kg). That case had occurred in an “endemic area for tuberculosis,” and the patient had been screened before entry but only via a sputum sample.

“Prior to these events, the patient received high-dose corticosteroids, a known risk factor for reactivation of TB, and thus the potential additive contribution of mavrilimumab, if any, is uncertain.” Dr. Pupim said.

“Thrombotic events, another known complication of COVID-19, occurred in the placebo arm only,” she added.

Dr. Pano commented that the study has now “seamlessly continued to phase 3. So, basically, we did not stop the study. At the end of phase 2, we just locked the database and collected the data.” Both the 6 mg/kg and 10 mg/kg are being studied, but it’s “very likely [that] 6 mg/kg could be the dose that we may bring forward to the clinic in terms of registration, but that’s at this point in time. We will need to wait for the phase 3 data,” he observed. Those findings will hopefully be available later this year.

Kiniksa funded the study. Dr. Pupim, Dr. Pano, and multiple study coinvestigators are employees of the company.

Dr. Schulze-Koops was not involved in the study and had no specific disclosures. Dr. Conway had no financial disclosures to make in relation to his comments.

Inhibiting granulocyte/macrophage–colony stimulating factor (GM-CSF) with mavrilimumab prevented some patients with severe COVID-19 pneumonia and hyperinflammation from needing mechanical ventilation and reduced their risk of dying versus placebo in a phase 2 study.

There was no difference in outcomes between the two doses of mavrilimumab used in the trial (6 mg/kg or 10 mg/kg) and combined data showed a higher percentage of patients achieving the primary endpoint of being alive and free of mechanical ventilation at 29 days, at 87%, versus placebo, at 74%.

The P value was 0.12, “which achieved the prespecified evidentiary standard of 0.2,” according to Lara Pupim, MD, vice president of clinical research and development at Kiniksa Pharmaceuticals in Lexington, Mass.

Importantly, there was a 61% reduction in the risk of dying if patients had received mavrilimumab rather than placebo, she reported at the annual European Congress of Rheumatology. Mortality at day 29 was 21% in the placebo arm but just 8% in the combined mavrilimumab arms (P = .07).

Hendrik Schulze-Koops, MD, called it a “surprising study” and that “the outcome is very spectacular” in his short appraisal of the study during the Clinical Highlights session on the final day of the congress.

Mavrilimumab was “a compound that we would not have thought that would have such an impact on the outcome of COVID-19 infected patients,” Dr. Schulze-Koops of Ludwig Maximilian University of Munich added.

In this small study, “there was a consistent suggestion of a biological effect across key endpoints,” Richard Conway, MBChB, PhD, a consultant rheumatologist at St. James’s Hospital in Dublin, pointed out in an interview.

“Similar to tocilizumab, the benefits with mavrilimumab appear to be in addition to those seen with glucocorticoids, as 96% of patients received dexamethasone,” Dr. Conway observed. Furthermore, nearly one-third received antiviral or remdesivir treatment.

“This study was likely underpowered to assess a clinically meaningful benefit,” he said, adding that “there is insufficient evidence at present to begin using mavrilimumab as an alternative to currently available agents.” That said, “these results are promising for future studies.”

Rationale for GM-CSF inhibition with mavrilimumab in COVID-19 pneumonia

“The cytokine GM-CSF is vital to both lung homeostasis and regulation of inflammation in autoimmunity,” Dr. Pupim explained.

She added that “GM-CSF is implicated in the mechanism of aberrant immune cell infiltration and activation in the lungs, and it may contribute to respiratory failure and death in patients with severe COVID-19 pneumonia and systemic hyperinflammation.”

The efficacy and safety of blocking GM-CSF with mavrilimumab have been shown previously in phase 2 studies in other diseases, Dr. Pupim noted. This includes patients with rheumatoid arthritis and those with giant cell arteritis.

“It was hypothesized that GM-CSF receptor–alpha blockade may reduce infiltration of pathogenic cells into the lung and may suppress inflammation in COVID-19 pneumonia in hyperinflammation,” she explained.

Study details and other outcome results

The study presented by Dr. Pupim was a phase 2/3 double-blind, placebo-controlled trial predominantly conducted in Brazil, the United States, and South Africa, with some participation in Peru and Chile.

Patients were eligible for inclusion if they had had a positive COVID-19 test within 14 days of randomization and had been hospitalized but not ventilated. Evidence of bilateral pneumonia on chest x-ray or CT scan and clinical laboratory evidence indicative of hyperinflammation were also prerequisites for study enrollment.

The ongoing study comprised two cohorts, Dr. Pupim explained: patients who have not been ventilated and those who have recently been ventilated. Dr. Pupim presented the data on the nonventilated cohort, noting that there was a total of 116 patients aged a mean of 57 years.

Patients were randomized to one of three treatment arms: two groups received a single intravenous infusion of mavrilimumab, either 6 mg/kg or 10 mg/kg, and the third group got a placebo.

“Using a time-to-event approach, looking at mechanical ventilation-free survival, mavrilimumab recipients experienced a 65% reduction in the risk of mechanical ventilation or death,” Dr. Pupim said (P = .0175).

“Separation in the Kaplan-Meier curves was evident very early after study drug administration,” she added.

There were trends toward a faster benefit with mavrilimumab than placebo in two other key secondary endpoints: the median time to achieving a two-point clinical improvement (7 vs. 11 days) and the median time to room air (7 vs. 9 days).

Timing of mavrilimumab administration and safety

Study coauthor and chief clinical development officer at Kiniksa, Arian Pano, MD, answered questions on the presentation. When asked about the timing of giving mavrilimumab, he said: “Based on these data it is before they go to ventilation, as soon as you have symptoms of hyperinflammation and a need for oxygen.”

Mavrilimumab is given as a single infusion “and has been well tolerated; virtually no interruptions occurred in this study.”

No serious adverse events related to mavrilimumab were seen, and adverse events, including secondary infections, which are known complications of COVID-19, occurred less frequently in mavrilimumab recipients, compared with placebo.

Dr. Pupim reported that there was a case of tuberculosis in one patient treated with mavrilimumab (10 mg/kg). That case had occurred in an “endemic area for tuberculosis,” and the patient had been screened before entry but only via a sputum sample.

“Prior to these events, the patient received high-dose corticosteroids, a known risk factor for reactivation of TB, and thus the potential additive contribution of mavrilimumab, if any, is uncertain.” Dr. Pupim said.

“Thrombotic events, another known complication of COVID-19, occurred in the placebo arm only,” she added.

Dr. Pano commented that the study has now “seamlessly continued to phase 3. So, basically, we did not stop the study. At the end of phase 2, we just locked the database and collected the data.” Both the 6 mg/kg and 10 mg/kg are being studied, but it’s “very likely [that] 6 mg/kg could be the dose that we may bring forward to the clinic in terms of registration, but that’s at this point in time. We will need to wait for the phase 3 data,” he observed. Those findings will hopefully be available later this year.

Kiniksa funded the study. Dr. Pupim, Dr. Pano, and multiple study coinvestigators are employees of the company.

Dr. Schulze-Koops was not involved in the study and had no specific disclosures. Dr. Conway had no financial disclosures to make in relation to his comments.

Background: Providing hospital-level care at home for select patients has proven to reduce health care cost, usage, and readmission rates, while maintaining quality and safety in other developed countries but few studies exist in the United States.

Dr. Persaud is a hospitalist, Beth Israel Deaconess Medical Center, and instructor in medicine, Harvard Medical School, both in Boston.

Background: Providing hospital-level care at home for select patients has proven to reduce health care cost, usage, and readmission rates, while maintaining quality and safety in other developed countries but few studies exist in the United States.

Dr. Persaud is a hospitalist, Beth Israel Deaconess Medical Center, and instructor in medicine, Harvard Medical School, both in Boston.

Background: Providing hospital-level care at home for select patients has proven to reduce health care cost, usage, and readmission rates, while maintaining quality and safety in other developed countries but few studies exist in the United States.

Dr. Persaud is a hospitalist, Beth Israel Deaconess Medical Center, and instructor in medicine, Harvard Medical School, both in Boston.

I remember sitting at the pool in San Diego. I had been there before many years prior – one of my first medical conferences. I remember the clinking of metal sail stays in the morning breeze.

Flying out this time I packed a few surgical masks. I guiltily picked up an N95 from the hospital floors the day before leaving, but then left it at home thinking it overkill. I still have it in a ziplock bag a year later – it’s our emergency “what-if-we-have-to-care-for-one-another-with-COVID-in-this-tiny-house-full-of-kids” N95. Not that my husband has been fit tested. At the time, neither was I.

I returned after the conference to befuddlement over how we might fit test thousands of people, racing COVID to the front door. An overly complicated task, as we didn’t even know who was supposed to be responsible for orchestrating such an effort. We didn’t even know if we could spare the N95s.

Still in California, I sat by the pool wondering if anyone would acknowledge the impending new reality. At the conference we were told “don’t shake hands, don’t touch your face, wash your hands a lot.” I gave a workshop without a mask. I ate dinner in an actual restaurant worried only about gluten free soy sauce. I sat in a lecture hall with almost 5,000 people. I started to have a conversation with a friend from Seattle, but he needed to leave because they found a positive patient in his hospital. I listened to a prerecorded webinar by the pool from our chief safety officer saying there was a plan. I was not reassured.

When we flew home the world had already changed. There were patients in New York now. Masks had appeared in the airport news stand. Yet we breathed the air in the closed space of the red eye and forgot to be concerned. At work that Monday I asked my team – fist to 5, how worried are you about this? Brave faces and side eyes at each other and a lot of 1s or 2s held up in the air. My job this week, I told them, is to get you all to a 5.

I was working with a resident who 2 months prior I had told, as we worked together in the lounge, I don’t think you’re going to China on vacation. She hadn’t gone, of course. I wasn’t going on spring break either. On one of my last train rides a commuter friend (remember those?) told me we’ll all feel a lot better once we realize that none of us are going to get to do any of the things we want to do.

The med students were still there, helping the team and hanging onto their education. I told everyone not to see any patient with a respiratory complaint until we first discussed the case. On the third day of service I had to call infection control because a hypoxic febrile patient had come to the floor without isolation orders. “Are we testing?” No, I was informed, she hadn’t had exposures, hadn’t travelled. Speechless that we were screening for travel to Italy while living with one tiny state between us and the American epicenter, I can now recall thinking that our infection control officer did not sound well rested.

My N95 was still in a baggy at home. The PAPRS hadn’t appeared yet. Literally no one could agree what kind of mask the CDC or infection control or the ID consultant of the day recommended – today we are using surgical masks, I was told. Thursday will likely be different. “Anyway, she doesn’t sound like she has it.” I walked to the floors.

My med student started presenting our septic viral pneumonia patient including the very well done exam that I previously forbade him from obtaining. What happened to not seeing respiratory patients, I asked. Oh, they said, well night float said it didn’t sound like COVID. Insufficiently convinced by our second year resident’s unjustifiably overconfident, though ultimately correct, assessment – I held my head in my hands and give my first hallway COVID chalk talk of the new era. Complete with telling the team to question everything they thought they knew now including everything I said except “be careful.” That was about when Philadelphia ran out of toilet paper.

That weekend I sat in front of a bay of computers as our Medical Officer of the Day. Air traffic control for ED patients coming in for a landing on medical teams, I watched the new biohazard warnings line up indicating respiratory isolation patients waiting for a bed. I watched CRPs and D-dimers, and looked for leukopenia. I vowed I would follow up on tests to hone my COVID illness script. I soon realized that tests lie anyway.

By the end of that week we’d fallen through the looking glass. The old rules didn’t apply. We weren’t going to China, or Arizona; we didn’t know when the med students were coming back; the jobs we had were not the jobs we signed up for but were those that the world needed us to do; we couldn’t trust our intuition or our tests; we had no experts – and yet we started to grow the humble beginnings of expertise like spring garden sprouts.

In a chaotic world, seeds of order take shape and then scatter like a screensaver. The skills needed to manage chaos are different from those that leaders use in simple ordered times. Order cannot be pulled from chaos by force of will or cleverness, nor can it be delegated, cascaded, demanded, or launched. Order emerges when communities that are receptive to learning see patterns through noise, and slowly, lovingly, coax moments of stability into being.
 

Dr. Jaffe is division director for hospital medicine in the Department of Medicine at Thomas Jefferson University Hospital in Philadelphia.

I remember sitting at the pool in San Diego. I had been there before many years prior – one of my first medical conferences. I remember the clinking of metal sail stays in the morning breeze.

Flying out this time I packed a few surgical masks. I guiltily picked up an N95 from the hospital floors the day before leaving, but then left it at home thinking it overkill. I still have it in a ziplock bag a year later – it’s our emergency “what-if-we-have-to-care-for-one-another-with-COVID-in-this-tiny-house-full-of-kids” N95. Not that my husband has been fit tested. At the time, neither was I.

I returned after the conference to befuddlement over how we might fit test thousands of people, racing COVID to the front door. An overly complicated task, as we didn’t even know who was supposed to be responsible for orchestrating such an effort. We didn’t even know if we could spare the N95s.

Still in California, I sat by the pool wondering if anyone would acknowledge the impending new reality. At the conference we were told “don’t shake hands, don’t touch your face, wash your hands a lot.” I gave a workshop without a mask. I ate dinner in an actual restaurant worried only about gluten free soy sauce. I sat in a lecture hall with almost 5,000 people. I started to have a conversation with a friend from Seattle, but he needed to leave because they found a positive patient in his hospital. I listened to a prerecorded webinar by the pool from our chief safety officer saying there was a plan. I was not reassured.

When we flew home the world had already changed. There were patients in New York now. Masks had appeared in the airport news stand. Yet we breathed the air in the closed space of the red eye and forgot to be concerned. At work that Monday I asked my team – fist to 5, how worried are you about this? Brave faces and side eyes at each other and a lot of 1s or 2s held up in the air. My job this week, I told them, is to get you all to a 5.

I was working with a resident who 2 months prior I had told, as we worked together in the lounge, I don’t think you’re going to China on vacation. She hadn’t gone, of course. I wasn’t going on spring break either. On one of my last train rides a commuter friend (remember those?) told me we’ll all feel a lot better once we realize that none of us are going to get to do any of the things we want to do.

The med students were still there, helping the team and hanging onto their education. I told everyone not to see any patient with a respiratory complaint until we first discussed the case. On the third day of service I had to call infection control because a hypoxic febrile patient had come to the floor without isolation orders. “Are we testing?” No, I was informed, she hadn’t had exposures, hadn’t travelled. Speechless that we were screening for travel to Italy while living with one tiny state between us and the American epicenter, I can now recall thinking that our infection control officer did not sound well rested.

My N95 was still in a baggy at home. The PAPRS hadn’t appeared yet. Literally no one could agree what kind of mask the CDC or infection control or the ID consultant of the day recommended – today we are using surgical masks, I was told. Thursday will likely be different. “Anyway, she doesn’t sound like she has it.” I walked to the floors.

My med student started presenting our septic viral pneumonia patient including the very well done exam that I previously forbade him from obtaining. What happened to not seeing respiratory patients, I asked. Oh, they said, well night float said it didn’t sound like COVID. Insufficiently convinced by our second year resident’s unjustifiably overconfident, though ultimately correct, assessment – I held my head in my hands and give my first hallway COVID chalk talk of the new era. Complete with telling the team to question everything they thought they knew now including everything I said except “be careful.” That was about when Philadelphia ran out of toilet paper.

That weekend I sat in front of a bay of computers as our Medical Officer of the Day. Air traffic control for ED patients coming in for a landing on medical teams, I watched the new biohazard warnings line up indicating respiratory isolation patients waiting for a bed. I watched CRPs and D-dimers, and looked for leukopenia. I vowed I would follow up on tests to hone my COVID illness script. I soon realized that tests lie anyway.

By the end of that week we’d fallen through the looking glass. The old rules didn’t apply. We weren’t going to China, or Arizona; we didn’t know when the med students were coming back; the jobs we had were not the jobs we signed up for but were those that the world needed us to do; we couldn’t trust our intuition or our tests; we had no experts – and yet we started to grow the humble beginnings of expertise like spring garden sprouts.

In a chaotic world, seeds of order take shape and then scatter like a screensaver. The skills needed to manage chaos are different from those that leaders use in simple ordered times. Order cannot be pulled from chaos by force of will or cleverness, nor can it be delegated, cascaded, demanded, or launched. Order emerges when communities that are receptive to learning see patterns through noise, and slowly, lovingly, coax moments of stability into being.
 

Dr. Jaffe is division director for hospital medicine in the Department of Medicine at Thomas Jefferson University Hospital in Philadelphia.

I remember sitting at the pool in San Diego. I had been there before many years prior – one of my first medical conferences. I remember the clinking of metal sail stays in the morning breeze.

Flying out this time I packed a few surgical masks. I guiltily picked up an N95 from the hospital floors the day before leaving, but then left it at home thinking it overkill. I still have it in a ziplock bag a year later – it’s our emergency “what-if-we-have-to-care-for-one-another-with-COVID-in-this-tiny-house-full-of-kids” N95. Not that my husband has been fit tested. At the time, neither was I.

I returned after the conference to befuddlement over how we might fit test thousands of people, racing COVID to the front door. An overly complicated task, as we didn’t even know who was supposed to be responsible for orchestrating such an effort. We didn’t even know if we could spare the N95s.

Still in California, I sat by the pool wondering if anyone would acknowledge the impending new reality. At the conference we were told “don’t shake hands, don’t touch your face, wash your hands a lot.” I gave a workshop without a mask. I ate dinner in an actual restaurant worried only about gluten free soy sauce. I sat in a lecture hall with almost 5,000 people. I started to have a conversation with a friend from Seattle, but he needed to leave because they found a positive patient in his hospital. I listened to a prerecorded webinar by the pool from our chief safety officer saying there was a plan. I was not reassured.

When we flew home the world had already changed. There were patients in New York now. Masks had appeared in the airport news stand. Yet we breathed the air in the closed space of the red eye and forgot to be concerned. At work that Monday I asked my team – fist to 5, how worried are you about this? Brave faces and side eyes at each other and a lot of 1s or 2s held up in the air. My job this week, I told them, is to get you all to a 5.

I was working with a resident who 2 months prior I had told, as we worked together in the lounge, I don’t think you’re going to China on vacation. She hadn’t gone, of course. I wasn’t going on spring break either. On one of my last train rides a commuter friend (remember those?) told me we’ll all feel a lot better once we realize that none of us are going to get to do any of the things we want to do.

The med students were still there, helping the team and hanging onto their education. I told everyone not to see any patient with a respiratory complaint until we first discussed the case. On the third day of service I had to call infection control because a hypoxic febrile patient had come to the floor without isolation orders. “Are we testing?” No, I was informed, she hadn’t had exposures, hadn’t travelled. Speechless that we were screening for travel to Italy while living with one tiny state between us and the American epicenter, I can now recall thinking that our infection control officer did not sound well rested.

My N95 was still in a baggy at home. The PAPRS hadn’t appeared yet. Literally no one could agree what kind of mask the CDC or infection control or the ID consultant of the day recommended – today we are using surgical masks, I was told. Thursday will likely be different. “Anyway, she doesn’t sound like she has it.” I walked to the floors.

My med student started presenting our septic viral pneumonia patient including the very well done exam that I previously forbade him from obtaining. What happened to not seeing respiratory patients, I asked. Oh, they said, well night float said it didn’t sound like COVID. Insufficiently convinced by our second year resident’s unjustifiably overconfident, though ultimately correct, assessment – I held my head in my hands and give my first hallway COVID chalk talk of the new era. Complete with telling the team to question everything they thought they knew now including everything I said except “be careful.” That was about when Philadelphia ran out of toilet paper.

That weekend I sat in front of a bay of computers as our Medical Officer of the Day. Air traffic control for ED patients coming in for a landing on medical teams, I watched the new biohazard warnings line up indicating respiratory isolation patients waiting for a bed. I watched CRPs and D-dimers, and looked for leukopenia. I vowed I would follow up on tests to hone my COVID illness script. I soon realized that tests lie anyway.

By the end of that week we’d fallen through the looking glass. The old rules didn’t apply. We weren’t going to China, or Arizona; we didn’t know when the med students were coming back; the jobs we had were not the jobs we signed up for but were those that the world needed us to do; we couldn’t trust our intuition or our tests; we had no experts – and yet we started to grow the humble beginnings of expertise like spring garden sprouts.

In a chaotic world, seeds of order take shape and then scatter like a screensaver. The skills needed to manage chaos are different from those that leaders use in simple ordered times. Order cannot be pulled from chaos by force of will or cleverness, nor can it be delegated, cascaded, demanded, or launched. Order emerges when communities that are receptive to learning see patterns through noise, and slowly, lovingly, coax moments of stability into being.
 

Dr. Jaffe is division director for hospital medicine in the Department of Medicine at Thomas Jefferson University Hospital in Philadelphia.

Background: With more than 500 cases of NSF reported during 1997-2007, a black box warning advises against use of all GBCAs in at-risk CKD patients. However, newer literature has shown that group II GBCAs may have lower risks of causing NSF. The risk to patients with CKD IV and V is not clear.

Dr. Midha is a hospitalist at Beth Israel Deaconess Medical Center, instructor of medicine, Boston University, and part-time instructor in medicine, Harvard Medical School, all in Boston.

Background: With more than 500 cases of NSF reported during 1997-2007, a black box warning advises against use of all GBCAs in at-risk CKD patients. However, newer literature has shown that group II GBCAs may have lower risks of causing NSF. The risk to patients with CKD IV and V is not clear.

Dr. Midha is a hospitalist at Beth Israel Deaconess Medical Center, instructor of medicine, Boston University, and part-time instructor in medicine, Harvard Medical School, all in Boston.

Background: With more than 500 cases of NSF reported during 1997-2007, a black box warning advises against use of all GBCAs in at-risk CKD patients. However, newer literature has shown that group II GBCAs may have lower risks of causing NSF. The risk to patients with CKD IV and V is not clear.

Dr. Midha is a hospitalist at Beth Israel Deaconess Medical Center, instructor of medicine, Boston University, and part-time instructor in medicine, Harvard Medical School, all in Boston.

The CDC director is urging parents to vaccinate their teenagers against COVID-19, citing a study that shows increasing hospitalizations rates for adolescents.

“I am deeply concerned by the numbers of hospitalized adolescents and saddened to see the number of adolescents who required treatment in intensive care units or mechanical ventilation,” CDC Director Rochelle Walensky, MD, said in a statement.

While urging teenagers to wear masks and take precautions around others, she asked “parents, relatives, and close friends to join me and talk with teens about the importance of these prevention strategies and to encourage them to get vaccinated.”

Dr. Walensky referred to the CDC’s Morbidity and Mortality Weekly Report that showed adolescent hospitalizations peaked at 2.1 per 100,000 in early January 2021, then dropped to 0.6 per 100,000 in mid-March.

Alarmingly, hospitalizations rose to 1.3 per 100,000 in April, and a number of teens required serious interventions.

“Among hospitalized adolescents, nearly one-third required intensive care unit admission, and 5% required invasive mechanical ventilation,” the report said. No deaths occurred.

The study looked at 376 adolescents aged 12-17 who were hospitalized and tested positive for coronavirus. Of that group, 204 were hospitalized for COVID-19 and the other 172 were hospitalized for reasons not directly related to COVID-19.

Of the 204 hospitalized for COVID-19, 70.6% had an underlying medical condition such as obesity or chronic lung disease.

The study noted that children and teenagers have lower hospitalization rates and generally show less severe symptoms than do older people.

Possible causes for the rise in adolescent COVID-19 hospitalizations include the arrival of variants, the growing number of children returning to in-person education, and the changes in mask-wearing and other safety precautions, the study said.

The American Academy of Pediatrics said that as of May 27, 4 million children have tested positive for COVID-19 since the pandemic began, with about 34,500 new child cases reported for the week ending May 27.

The AAP said children have represented 14.1% of total cases since the pandemic began, but for the week ending May 27, children represented 24.3% of new reported weekly COVID-19 cases.

On May 10, the FDA granted emergency use authorization for the Pfizer coronavirus vaccine to be given to children aged 12-15 years. Previously, the FDA had authorized the Pfizer vaccine for people aged 16 years and up, whereas the Moderna and Johnson & Johnson vaccines are authorized for people aged 18 years and up.

“Vaccination is our way out of this pandemic,” Dr. Walensky said in her statement. “I continue to see promising signs in CDC data that we are nearing the end of this pandemic in this country; however, we all have to do our part and get vaccinated to cross the finish line.”
 

A version of this article was first published on WebMD.com.

The CDC director is urging parents to vaccinate their teenagers against COVID-19, citing a study that shows increasing hospitalizations rates for adolescents.

“I am deeply concerned by the numbers of hospitalized adolescents and saddened to see the number of adolescents who required treatment in intensive care units or mechanical ventilation,” CDC Director Rochelle Walensky, MD, said in a statement.

While urging teenagers to wear masks and take precautions around others, she asked “parents, relatives, and close friends to join me and talk with teens about the importance of these prevention strategies and to encourage them to get vaccinated.”

Dr. Walensky referred to the CDC’s Morbidity and Mortality Weekly Report that showed adolescent hospitalizations peaked at 2.1 per 100,000 in early January 2021, then dropped to 0.6 per 100,000 in mid-March.

Alarmingly, hospitalizations rose to 1.3 per 100,000 in April, and a number of teens required serious interventions.

“Among hospitalized adolescents, nearly one-third required intensive care unit admission, and 5% required invasive mechanical ventilation,” the report said. No deaths occurred.

The study looked at 376 adolescents aged 12-17 who were hospitalized and tested positive for coronavirus. Of that group, 204 were hospitalized for COVID-19 and the other 172 were hospitalized for reasons not directly related to COVID-19.

Of the 204 hospitalized for COVID-19, 70.6% had an underlying medical condition such as obesity or chronic lung disease.

The study noted that children and teenagers have lower hospitalization rates and generally show less severe symptoms than do older people.

Possible causes for the rise in adolescent COVID-19 hospitalizations include the arrival of variants, the growing number of children returning to in-person education, and the changes in mask-wearing and other safety precautions, the study said.

The American Academy of Pediatrics said that as of May 27, 4 million children have tested positive for COVID-19 since the pandemic began, with about 34,500 new child cases reported for the week ending May 27.

The AAP said children have represented 14.1% of total cases since the pandemic began, but for the week ending May 27, children represented 24.3% of new reported weekly COVID-19 cases.

On May 10, the FDA granted emergency use authorization for the Pfizer coronavirus vaccine to be given to children aged 12-15 years. Previously, the FDA had authorized the Pfizer vaccine for people aged 16 years and up, whereas the Moderna and Johnson & Johnson vaccines are authorized for people aged 18 years and up.

“Vaccination is our way out of this pandemic,” Dr. Walensky said in her statement. “I continue to see promising signs in CDC data that we are nearing the end of this pandemic in this country; however, we all have to do our part and get vaccinated to cross the finish line.”
 

A version of this article was first published on WebMD.com.

The CDC director is urging parents to vaccinate their teenagers against COVID-19, citing a study that shows increasing hospitalizations rates for adolescents.

“I am deeply concerned by the numbers of hospitalized adolescents and saddened to see the number of adolescents who required treatment in intensive care units or mechanical ventilation,” CDC Director Rochelle Walensky, MD, said in a statement.

While urging teenagers to wear masks and take precautions around others, she asked “parents, relatives, and close friends to join me and talk with teens about the importance of these prevention strategies and to encourage them to get vaccinated.”

Dr. Walensky referred to the CDC’s Morbidity and Mortality Weekly Report that showed adolescent hospitalizations peaked at 2.1 per 100,000 in early January 2021, then dropped to 0.6 per 100,000 in mid-March.

Alarmingly, hospitalizations rose to 1.3 per 100,000 in April, and a number of teens required serious interventions.

“Among hospitalized adolescents, nearly one-third required intensive care unit admission, and 5% required invasive mechanical ventilation,” the report said. No deaths occurred.

The study looked at 376 adolescents aged 12-17 who were hospitalized and tested positive for coronavirus. Of that group, 204 were hospitalized for COVID-19 and the other 172 were hospitalized for reasons not directly related to COVID-19.

Of the 204 hospitalized for COVID-19, 70.6% had an underlying medical condition such as obesity or chronic lung disease.

The study noted that children and teenagers have lower hospitalization rates and generally show less severe symptoms than do older people.

Possible causes for the rise in adolescent COVID-19 hospitalizations include the arrival of variants, the growing number of children returning to in-person education, and the changes in mask-wearing and other safety precautions, the study said.

The American Academy of Pediatrics said that as of May 27, 4 million children have tested positive for COVID-19 since the pandemic began, with about 34,500 new child cases reported for the week ending May 27.

The AAP said children have represented 14.1% of total cases since the pandemic began, but for the week ending May 27, children represented 24.3% of new reported weekly COVID-19 cases.

On May 10, the FDA granted emergency use authorization for the Pfizer coronavirus vaccine to be given to children aged 12-15 years. Previously, the FDA had authorized the Pfizer vaccine for people aged 16 years and up, whereas the Moderna and Johnson & Johnson vaccines are authorized for people aged 18 years and up.

“Vaccination is our way out of this pandemic,” Dr. Walensky said in her statement. “I continue to see promising signs in CDC data that we are nearing the end of this pandemic in this country; however, we all have to do our part and get vaccinated to cross the finish line.”
 

A version of this article was first published on WebMD.com.

Background: Prior studies have examined the impact of hospital system mergers on health care costs, but few studies have previously examined impact on quality and patient experience.

Study design: Retrospective, difference-in-difference analysis.

Setting: 2,232 U.S. hospitals during 2007-2016.

Synopsis: The authors identified 2,232 hospitals, including 246 hospitals that were acquired between 2009 and 2013 and 1,986 control hospitals that were not acquired during this period. They used a difference-in-difference analysis to compare hospital performance on quality and patient experience measures from before and after an acquisition to concurrent changes in control hospitals. Hospital acquisition was associated with a significant decline in measured patient experience. There was no significant differential change in 30-day readmission or mortality. Although there was an association between acquisition and significant improvement in clinical process metrics, the authors found that this improvement occurred almost entirely prior to acquisition.

Bottom line: Hospital acquisition was associated with worse experience for patients and had no significant impact on readmission or mortality rates.

Citation: Beaulieu ND et al. Changes in quality of care after hospital mergers and acquisitions. N Engl J Med. 2020 Jan 2;382:51-9.

Dr. Midha is a hospitalist at Beth Israel Deaconess Medical Center, instructor of medicine, Boston University, and part-time instructor in medicine, Harvard Medical School, all in Boston.

Background: Prior studies have examined the impact of hospital system mergers on health care costs, but few studies have previously examined impact on quality and patient experience.

Study design: Retrospective, difference-in-difference analysis.

Setting: 2,232 U.S. hospitals during 2007-2016.

Synopsis: The authors identified 2,232 hospitals, including 246 hospitals that were acquired between 2009 and 2013 and 1,986 control hospitals that were not acquired during this period. They used a difference-in-difference analysis to compare hospital performance on quality and patient experience measures from before and after an acquisition to concurrent changes in control hospitals. Hospital acquisition was associated with a significant decline in measured patient experience. There was no significant differential change in 30-day readmission or mortality. Although there was an association between acquisition and significant improvement in clinical process metrics, the authors found that this improvement occurred almost entirely prior to acquisition.

Bottom line: Hospital acquisition was associated with worse experience for patients and had no significant impact on readmission or mortality rates.

Citation: Beaulieu ND et al. Changes in quality of care after hospital mergers and acquisitions. N Engl J Med. 2020 Jan 2;382:51-9.

Dr. Midha is a hospitalist at Beth Israel Deaconess Medical Center, instructor of medicine, Boston University, and part-time instructor in medicine, Harvard Medical School, all in Boston.

Background: Prior studies have examined the impact of hospital system mergers on health care costs, but few studies have previously examined impact on quality and patient experience.

Study design: Retrospective, difference-in-difference analysis.

Setting: 2,232 U.S. hospitals during 2007-2016.

Synopsis: The authors identified 2,232 hospitals, including 246 hospitals that were acquired between 2009 and 2013 and 1,986 control hospitals that were not acquired during this period. They used a difference-in-difference analysis to compare hospital performance on quality and patient experience measures from before and after an acquisition to concurrent changes in control hospitals. Hospital acquisition was associated with a significant decline in measured patient experience. There was no significant differential change in 30-day readmission or mortality. Although there was an association between acquisition and significant improvement in clinical process metrics, the authors found that this improvement occurred almost entirely prior to acquisition.

Bottom line: Hospital acquisition was associated with worse experience for patients and had no significant impact on readmission or mortality rates.

Citation: Beaulieu ND et al. Changes in quality of care after hospital mergers and acquisitions. N Engl J Med. 2020 Jan 2;382:51-9.

Dr. Midha is a hospitalist at Beth Israel Deaconess Medical Center, instructor of medicine, Boston University, and part-time instructor in medicine, Harvard Medical School, all in Boston.

Converge 2021 session

Racial and Gender Equity in Your PHM Program

Presenters

Jorge Ganem, MD, FAAP, and Vanessa N. Durand, DO, FAAP

Session summary

Dr. Ganem, associate professor of pediatrics at the University of Texas at Austin and director of pediatric hospital medicine at Dell Children’s Medical Center, and Dr. Durand, assistant professor of pediatrics at Drexel University and pediatric hospitalist at St. Christopher’s Hospital for Children, Philadelphia, presented an engaging session regarding gender equity in the workplace during SHM Converge 2021.

Dr. Ganem and Dr. Durand first presented data to illustrate the gender equity problem. They touched on the mental burden underrepresented minorities face professionally. Dr. Ganem and Dr. Durand discussed cognitive biases, defined allyship, sponsorship, and mentorship and shared how to distinguish between the three. They concluded their session with concrete ways to narrow gaps in equity in hospital medicine programs.

The highlights of this session included evidence-based “best-practices” that pediatric hospital medicine divisions can adopt. One important theme was regarding metrics. Dr. Ganem and Dr. Durand shared how important it is to evaluate divisions for pay and diversity gaps. Armed with these data, programs can be more effective in developing solutions. Some solutions provided by the presenters included “blind” interviews where traditional “cognitive metrics” (i.e., board scores) are not shared with interviewers to minimize anchoring and confirmation biases. Instead, interviewers should focus on the experiences and attributes of the job that the applicant can hopefully embody. This could be accomplished using a holistic review tool from the Association of American Medical Colleges.

One of the most powerful ideas shared in this session was a quote from a Harvard student shown in a video regarding bias and racism where he said, “Nothing in all the world is more dangerous than sincere ignorance and conscious stupidity.” Changes will only happen if we make them happen.

Key takeaways

• Racial and gender equity are problems that are undeniable, even in pediatrics.
• Be wary of conscious biases and the mental burden placed unfairly on underrepresented minorities in your institution.
• Becoming an amplifier, a sponsor, or a champion are ways to make a small individual difference.
• Measure your program’s data and commit to making change using evidence-based actions and assessments aimed at decreasing bias and increasing equity.

References

Association of American Medical Colleges. Holistic Review. 2021. www.aamc.org/services/member-capacity-building/holistic-review.

Dr. Singh is a board-certified pediatric hospitalist at Stanford University and Lucile Packard Children’s Hospital Stanford, both in Palo Alto, Calif. He is a native Texan living in the San Francisco Bay area with his wife and two young boys. His nonclinical passions include bedside communication and inpatient health care information technology.

Converge 2021 session

Racial and Gender Equity in Your PHM Program

Presenters

Jorge Ganem, MD, FAAP, and Vanessa N. Durand, DO, FAAP

Session summary

Dr. Ganem, associate professor of pediatrics at the University of Texas at Austin and director of pediatric hospital medicine at Dell Children’s Medical Center, and Dr. Durand, assistant professor of pediatrics at Drexel University and pediatric hospitalist at St. Christopher’s Hospital for Children, Philadelphia, presented an engaging session regarding gender equity in the workplace during SHM Converge 2021.

Dr. Ganem and Dr. Durand first presented data to illustrate the gender equity problem. They touched on the mental burden underrepresented minorities face professionally. Dr. Ganem and Dr. Durand discussed cognitive biases, defined allyship, sponsorship, and mentorship and shared how to distinguish between the three. They concluded their session with concrete ways to narrow gaps in equity in hospital medicine programs.

The highlights of this session included evidence-based “best-practices” that pediatric hospital medicine divisions can adopt. One important theme was regarding metrics. Dr. Ganem and Dr. Durand shared how important it is to evaluate divisions for pay and diversity gaps. Armed with these data, programs can be more effective in developing solutions. Some solutions provided by the presenters included “blind” interviews where traditional “cognitive metrics” (i.e., board scores) are not shared with interviewers to minimize anchoring and confirmation biases. Instead, interviewers should focus on the experiences and attributes of the job that the applicant can hopefully embody. This could be accomplished using a holistic review tool from the Association of American Medical Colleges.

One of the most powerful ideas shared in this session was a quote from a Harvard student shown in a video regarding bias and racism where he said, “Nothing in all the world is more dangerous than sincere ignorance and conscious stupidity.” Changes will only happen if we make them happen.

Key takeaways

• Racial and gender equity are problems that are undeniable, even in pediatrics.
• Be wary of conscious biases and the mental burden placed unfairly on underrepresented minorities in your institution.
• Becoming an amplifier, a sponsor, or a champion are ways to make a small individual difference.
• Measure your program’s data and commit to making change using evidence-based actions and assessments aimed at decreasing bias and increasing equity.

References

Association of American Medical Colleges. Holistic Review. 2021. www.aamc.org/services/member-capacity-building/holistic-review.

Dr. Singh is a board-certified pediatric hospitalist at Stanford University and Lucile Packard Children’s Hospital Stanford, both in Palo Alto, Calif. He is a native Texan living in the San Francisco Bay area with his wife and two young boys. His nonclinical passions include bedside communication and inpatient health care information technology.

Converge 2021 session

Racial and Gender Equity in Your PHM Program

Presenters

Jorge Ganem, MD, FAAP, and Vanessa N. Durand, DO, FAAP

Session summary

Dr. Ganem, associate professor of pediatrics at the University of Texas at Austin and director of pediatric hospital medicine at Dell Children’s Medical Center, and Dr. Durand, assistant professor of pediatrics at Drexel University and pediatric hospitalist at St. Christopher’s Hospital for Children, Philadelphia, presented an engaging session regarding gender equity in the workplace during SHM Converge 2021.

Dr. Ganem and Dr. Durand first presented data to illustrate the gender equity problem. They touched on the mental burden underrepresented minorities face professionally. Dr. Ganem and Dr. Durand discussed cognitive biases, defined allyship, sponsorship, and mentorship and shared how to distinguish between the three. They concluded their session with concrete ways to narrow gaps in equity in hospital medicine programs.

The highlights of this session included evidence-based “best-practices” that pediatric hospital medicine divisions can adopt. One important theme was regarding metrics. Dr. Ganem and Dr. Durand shared how important it is to evaluate divisions for pay and diversity gaps. Armed with these data, programs can be more effective in developing solutions. Some solutions provided by the presenters included “blind” interviews where traditional “cognitive metrics” (i.e., board scores) are not shared with interviewers to minimize anchoring and confirmation biases. Instead, interviewers should focus on the experiences and attributes of the job that the applicant can hopefully embody. This could be accomplished using a holistic review tool from the Association of American Medical Colleges.

One of the most powerful ideas shared in this session was a quote from a Harvard student shown in a video regarding bias and racism where he said, “Nothing in all the world is more dangerous than sincere ignorance and conscious stupidity.” Changes will only happen if we make them happen.

Key takeaways

• Racial and gender equity are problems that are undeniable, even in pediatrics.
• Be wary of conscious biases and the mental burden placed unfairly on underrepresented minorities in your institution.
• Becoming an amplifier, a sponsor, or a champion are ways to make a small individual difference.
• Measure your program’s data and commit to making change using evidence-based actions and assessments aimed at decreasing bias and increasing equity.

References

Association of American Medical Colleges. Holistic Review. 2021. www.aamc.org/services/member-capacity-building/holistic-review.

Dr. Singh is a board-certified pediatric hospitalist at Stanford University and Lucile Packard Children’s Hospital Stanford, both in Palo Alto, Calif. He is a native Texan living in the San Francisco Bay area with his wife and two young boys. His nonclinical passions include bedside communication and inpatient health care information technology.