Hematology News

Erythema associated with chronic graft-versus-host disease (GVHD) after allogenic stem cell transplantation is likely to resolve regardless of when it appears, while sclerosis that develops more than 3 months after a chronic GVHD diagnosis is less likely to resolve, according to research presented during a plenary session at the annual meeting of the Society for Investigative Dermatology, held virtually.

In addition, greater improvement in erythema, as measured by body surface area (BSA) in the study was significantly associated with higher patient survival, Laura X. Baker, BS, a medical student at Vanderbilt University, and coinvestigators at Vanderbilt Dermatology Translational Research Clinic in Nashville, Tenn., said in her presentation.

This new significant association between erythema response and survival could inform future studies,” she said. “Our findings highlight the importance of thorough skin exams in chronic GVHD patients.”

Ms. Baker and colleagues performed a prospective, observational study of 242 patients with chronic GVHD and cutaneous manifestations, enrolled in the Chronic GVHD Consortium across nine centers between 2007 and 2012.

Patients had either erythema or sclerosis at the time of enrollment, which was considered incident if erythema or sclerosis appeared less than 3 months after diagnosis of chronic GVHD, or prevalent if erythema or sclerosis appeared 3 months or later after a chronic GVHD diagnosis. All patients were enrolled in the Chronic GVHD Consortium within 3 years of a transplant and were receiving systemic immunosuppressive therapy.

Transplant clinicians examined patients every 6 months, assessing clinical parameters such as skin involvement. Ms. Baker and colleagues used the 2005 National Institutes of Health (NIH) criteria to assess a complete response, a partial response, or no cutaneous response using measurements made by the transplant clinicians. The NIH criteria recommend calculating the change in BSA at the first follow-up visit to determine these changes (Pavletic S et al. Biol Blood Marrow Transplant. 2006 Mar;12[3]:252-66). Researchers also developed a Cox regression model to evaluate overall survival and non-relapse mortality.

Among those with erythema, 133 patients had incident cases and 52 had prevalent cases of cutaneous chronic GVHD. At first follow-up after a finding of cutaneous involvement, the mean BSA was 4.5%, but the median BSA was zero, “meaning that more than half of the patients had complete disappearance of any erythema by the first follow-up,” Ms. Baker said. By the second follow-up visit, 74% of patients with erythema had complete responses, 9% achieved a partial response, and 18% had no response. A similar complete response rate was seen among patients with prevalent cases.

Among patients with sclerosis, there were 43 incident and 47 prevalent cases. Among patients with incident sclerosis, 68% achieved a clear response, 2% a partial response, and 30% no response. But only 28% of those with prevalent sclerosis had a complete response, 4% had a partial response, and 68% had no response.

Most erythema showed a complete response by the first follow-up, and it was not dependent on time from cGVHD diagnosis, Ms. Baker said. However, while most sclerosis within 3 months of cGVHD diagnosis showed a response, sclerosis present beyond the initial 3 months did not generally respond by the first follow-up.

“These findings could inform clinical care and expectations in addition to guiding the selection of outcome measures and endpoint definitions in clinical trials,” she added.

The researchers also looked at overall survival and nonrelapse mortality among patients with incident and prevalent erythema. After adjustment for age and BSA at enrollment, patients with incident cases of erythema with a complete response had significantly better odds of overall survival compared with patients who had no clinical response (hazard ratio, 0.50; 95% confidence interval; 0.25-1.00; P = .05).

Overall survival was greater in patients with prevalent cases of erythema (HR, 0.29; 95% CI, 0.09-0.87; P = .03). Nonrelapse mortality was also significantly lower among prevalent cases with complete or partial clinical response for erythema (HR, 0.19; 95% CI, 0.06-0.64; P = .01).

In a subgroup analysis, 113 patients with incident cases of erythema that had other organ cGVHD had significantly greater overall survival than did patients without a clinical response (HR, 0.20; 95% CI, 0.08-0.46; P < .005). Median survival distance after the first follow-up between patients with and without a clinical response was 28.9 months among incident cases, and 33.7 months among prevalent erythema cases.

“We knew that erythema is not a direct cause of mortality,” Ms. Baker said. Our results suggest the association between erythema response and survival is important and could inform future study.”

The researchers noted their study was limited by transplant clinicians measuring BSA rather than dermatologists, patients being treated at top transplant centers, and their GVHD diagnosis being within 3 years of a transplant, which could limit generalizability of the findings.

This study was funded by a career development award from the U.S. Department of Veterans Affairs and grants from the National Institutes of Health/National Cancer Institute.

SOURCE: Baker L. SID 2020, Abstract 434.

Erythema associated with chronic graft-versus-host disease (GVHD) after allogenic stem cell transplantation is likely to resolve regardless of when it appears, while sclerosis that develops more than 3 months after a chronic GVHD diagnosis is less likely to resolve, according to research presented during a plenary session at the annual meeting of the Society for Investigative Dermatology, held virtually.

In addition, greater improvement in erythema, as measured by body surface area (BSA) in the study was significantly associated with higher patient survival, Laura X. Baker, BS, a medical student at Vanderbilt University, and coinvestigators at Vanderbilt Dermatology Translational Research Clinic in Nashville, Tenn., said in her presentation.

This new significant association between erythema response and survival could inform future studies,” she said. “Our findings highlight the importance of thorough skin exams in chronic GVHD patients.”

Ms. Baker and colleagues performed a prospective, observational study of 242 patients with chronic GVHD and cutaneous manifestations, enrolled in the Chronic GVHD Consortium across nine centers between 2007 and 2012.

Patients had either erythema or sclerosis at the time of enrollment, which was considered incident if erythema or sclerosis appeared less than 3 months after diagnosis of chronic GVHD, or prevalent if erythema or sclerosis appeared 3 months or later after a chronic GVHD diagnosis. All patients were enrolled in the Chronic GVHD Consortium within 3 years of a transplant and were receiving systemic immunosuppressive therapy.

Transplant clinicians examined patients every 6 months, assessing clinical parameters such as skin involvement. Ms. Baker and colleagues used the 2005 National Institutes of Health (NIH) criteria to assess a complete response, a partial response, or no cutaneous response using measurements made by the transplant clinicians. The NIH criteria recommend calculating the change in BSA at the first follow-up visit to determine these changes (Pavletic S et al. Biol Blood Marrow Transplant. 2006 Mar;12[3]:252-66). Researchers also developed a Cox regression model to evaluate overall survival and non-relapse mortality.

Among those with erythema, 133 patients had incident cases and 52 had prevalent cases of cutaneous chronic GVHD. At first follow-up after a finding of cutaneous involvement, the mean BSA was 4.5%, but the median BSA was zero, “meaning that more than half of the patients had complete disappearance of any erythema by the first follow-up,” Ms. Baker said. By the second follow-up visit, 74% of patients with erythema had complete responses, 9% achieved a partial response, and 18% had no response. A similar complete response rate was seen among patients with prevalent cases.

Among patients with sclerosis, there were 43 incident and 47 prevalent cases. Among patients with incident sclerosis, 68% achieved a clear response, 2% a partial response, and 30% no response. But only 28% of those with prevalent sclerosis had a complete response, 4% had a partial response, and 68% had no response.

Most erythema showed a complete response by the first follow-up, and it was not dependent on time from cGVHD diagnosis, Ms. Baker said. However, while most sclerosis within 3 months of cGVHD diagnosis showed a response, sclerosis present beyond the initial 3 months did not generally respond by the first follow-up.

“These findings could inform clinical care and expectations in addition to guiding the selection of outcome measures and endpoint definitions in clinical trials,” she added.

The researchers also looked at overall survival and nonrelapse mortality among patients with incident and prevalent erythema. After adjustment for age and BSA at enrollment, patients with incident cases of erythema with a complete response had significantly better odds of overall survival compared with patients who had no clinical response (hazard ratio, 0.50; 95% confidence interval; 0.25-1.00; P = .05).

Overall survival was greater in patients with prevalent cases of erythema (HR, 0.29; 95% CI, 0.09-0.87; P = .03). Nonrelapse mortality was also significantly lower among prevalent cases with complete or partial clinical response for erythema (HR, 0.19; 95% CI, 0.06-0.64; P = .01).

In a subgroup analysis, 113 patients with incident cases of erythema that had other organ cGVHD had significantly greater overall survival than did patients without a clinical response (HR, 0.20; 95% CI, 0.08-0.46; P < .005). Median survival distance after the first follow-up between patients with and without a clinical response was 28.9 months among incident cases, and 33.7 months among prevalent erythema cases.

“We knew that erythema is not a direct cause of mortality,” Ms. Baker said. Our results suggest the association between erythema response and survival is important and could inform future study.”

The researchers noted their study was limited by transplant clinicians measuring BSA rather than dermatologists, patients being treated at top transplant centers, and their GVHD diagnosis being within 3 years of a transplant, which could limit generalizability of the findings.

This study was funded by a career development award from the U.S. Department of Veterans Affairs and grants from the National Institutes of Health/National Cancer Institute.

SOURCE: Baker L. SID 2020, Abstract 434.

Erythema associated with chronic graft-versus-host disease (GVHD) after allogenic stem cell transplantation is likely to resolve regardless of when it appears, while sclerosis that develops more than 3 months after a chronic GVHD diagnosis is less likely to resolve, according to research presented during a plenary session at the annual meeting of the Society for Investigative Dermatology, held virtually.

In addition, greater improvement in erythema, as measured by body surface area (BSA) in the study was significantly associated with higher patient survival, Laura X. Baker, BS, a medical student at Vanderbilt University, and coinvestigators at Vanderbilt Dermatology Translational Research Clinic in Nashville, Tenn., said in her presentation.

This new significant association between erythema response and survival could inform future studies,” she said. “Our findings highlight the importance of thorough skin exams in chronic GVHD patients.”

Ms. Baker and colleagues performed a prospective, observational study of 242 patients with chronic GVHD and cutaneous manifestations, enrolled in the Chronic GVHD Consortium across nine centers between 2007 and 2012.

Patients had either erythema or sclerosis at the time of enrollment, which was considered incident if erythema or sclerosis appeared less than 3 months after diagnosis of chronic GVHD, or prevalent if erythema or sclerosis appeared 3 months or later after a chronic GVHD diagnosis. All patients were enrolled in the Chronic GVHD Consortium within 3 years of a transplant and were receiving systemic immunosuppressive therapy.

Transplant clinicians examined patients every 6 months, assessing clinical parameters such as skin involvement. Ms. Baker and colleagues used the 2005 National Institutes of Health (NIH) criteria to assess a complete response, a partial response, or no cutaneous response using measurements made by the transplant clinicians. The NIH criteria recommend calculating the change in BSA at the first follow-up visit to determine these changes (Pavletic S et al. Biol Blood Marrow Transplant. 2006 Mar;12[3]:252-66). Researchers also developed a Cox regression model to evaluate overall survival and non-relapse mortality.

Among those with erythema, 133 patients had incident cases and 52 had prevalent cases of cutaneous chronic GVHD. At first follow-up after a finding of cutaneous involvement, the mean BSA was 4.5%, but the median BSA was zero, “meaning that more than half of the patients had complete disappearance of any erythema by the first follow-up,” Ms. Baker said. By the second follow-up visit, 74% of patients with erythema had complete responses, 9% achieved a partial response, and 18% had no response. A similar complete response rate was seen among patients with prevalent cases.

Among patients with sclerosis, there were 43 incident and 47 prevalent cases. Among patients with incident sclerosis, 68% achieved a clear response, 2% a partial response, and 30% no response. But only 28% of those with prevalent sclerosis had a complete response, 4% had a partial response, and 68% had no response.

Most erythema showed a complete response by the first follow-up, and it was not dependent on time from cGVHD diagnosis, Ms. Baker said. However, while most sclerosis within 3 months of cGVHD diagnosis showed a response, sclerosis present beyond the initial 3 months did not generally respond by the first follow-up.

“These findings could inform clinical care and expectations in addition to guiding the selection of outcome measures and endpoint definitions in clinical trials,” she added.

The researchers also looked at overall survival and nonrelapse mortality among patients with incident and prevalent erythema. After adjustment for age and BSA at enrollment, patients with incident cases of erythema with a complete response had significantly better odds of overall survival compared with patients who had no clinical response (hazard ratio, 0.50; 95% confidence interval; 0.25-1.00; P = .05).

Overall survival was greater in patients with prevalent cases of erythema (HR, 0.29; 95% CI, 0.09-0.87; P = .03). Nonrelapse mortality was also significantly lower among prevalent cases with complete or partial clinical response for erythema (HR, 0.19; 95% CI, 0.06-0.64; P = .01).

In a subgroup analysis, 113 patients with incident cases of erythema that had other organ cGVHD had significantly greater overall survival than did patients without a clinical response (HR, 0.20; 95% CI, 0.08-0.46; P < .005). Median survival distance after the first follow-up between patients with and without a clinical response was 28.9 months among incident cases, and 33.7 months among prevalent erythema cases.

“We knew that erythema is not a direct cause of mortality,” Ms. Baker said. Our results suggest the association between erythema response and survival is important and could inform future study.”

The researchers noted their study was limited by transplant clinicians measuring BSA rather than dermatologists, patients being treated at top transplant centers, and their GVHD diagnosis being within 3 years of a transplant, which could limit generalizability of the findings.

This study was funded by a career development award from the U.S. Department of Veterans Affairs and grants from the National Institutes of Health/National Cancer Institute.

SOURCE: Baker L. SID 2020, Abstract 434.

A study that claims to be the first review of all the available evidence of the effectiveness of physical distancing, face masks, and eye protection to prevent spread of COVID-19 and other respiratory diseases has quantified the effectiveness of these protective measures. The study found that greater physical distancing from an exposed person significantly reduces risk of transmission and that N95 masks, particularly for health care workers, are more effective than other face coverings.

The meta-analysis, published online in The Lancet (2020 Jun 2; doi.org/10.1016/ S0140-6736(20)31142-9) also marks the first evaluation of these protective measures in both community and health care settings for COVID-19, the study authors stated.

“The risk for infection is highly dependent on distance to the individual infected and the type of face mask and eye protection worn,” wrote Derek K. Chu, MD, PhD, of McMaster University in Hamilton, Ont., and colleagues, reporting on behalf of the COVID-19 Systematic Urgent Review Group Effort, or SURGE.

The study reported that physical distancing of at least 1 meter, or about a yard, “seems to be strongly associated with a large protective effect,” but that distancing of 2 meters or about 6 feet could be more effective.

The study involved a systematic review of 172 observational studies across six continents that evaluated distance measures, face masks, and eye protection to prevent transmission between patients with confirmed or probable COVID-19, other severe acute respiratory syndrome (SARS) disease, and Middle East respiratory syndrome (MERS), and their family members, caregivers and health care workers up to May 3, 2020. The meta-analysis involved pooled estimates from 44 comparative studies with 25,697 participants, including seven studies of COVID-19 with 6,674 participants. None of the studies included in the meta-analysis were randomized clinical trials.

A subanalysis of 29 unadjusted and 9 adjusted studies found that the absolute risk of infection in proximity to an exposed individual was 12.8% at 1 m and 2.6% at 2 m. The risk remained constant even when the six COVID-19 studies in this subanalysis were isolated and regardless of being in a health care or non–health-care setting. Each meter of increased distance resulted in a doubling in the change in relative risk (P = .041).

The study also identified what Dr. Chu and colleagues characterized as a “large reduction” in infection risk with the use of both N95 or similar respirators or face masks, with an adjusted risk of infection of 3.1% with a face covering vs. a 17.4% without. The researchers also found a stronger association in health care settings vs. non–health care settings, with a relative risk of 0.3 vs. 0.56, respectively (P = .049). The protective effect of N95 or similar respirators was greater than other masks, with adjusted odds ratios of 0.04 vs. 0.33 (P = .09).

Eye protection was found to reduce the risk of infection to 5.5% vs. 16% without eye protection.

The study also identified potential barriers to social distancing and use of masks and eye protection: discomfort, resource use “linked with potentially decreased equity,” less clear communication, and a perceived lack of empathy on the part of providers toward patients.

Dr. Chu and colleagues wrote that more “high-quality” research, including randomized trials of the optimal physical distance and evaluation of different mask types in non–health care settings “is urgently needed.” They added, “Policymakers at all levels should, therefore, strive to address equity implications for groups with currently limited access to face masks and eye protection.”

The goal of this study was to “inform WHO guidance documents,” the study noted. “Governments and the public health community can use our results to give clear advice for community settings and healthcare workers on these protective measures to reduce infection risk,” said study co-leader Holger Schünemann, MD, MSc, PhD, of McMaster University.

Prof. Raina MacIntyre, MBBS, PhD, head of the biosecurity research program at the Kirby Institute at the University of New South Wales in Sydney, who authored the comment that accompanied the article, said that this study provides evidence for stronger PPE guidelines.

“The Centers for Disease Control and Prevention initially recommended N95s for health workers treating COVID-19 patients, but later downgraded this to surgical masks and even cloth masks and bandannas when there was a supply shortage,” she said. “This study shows that N95s are superior masks and should prompt a review of guidelines that recommend anything less for health workers.”

Recommending anything less than N95 masks for health workers is like sending troops into battle “unarmed or with bows and arrows against a fully armed enemy,” she said. “We are not talking about a device that costs hundreds or thousands of dollars; a N95 costs less than a dollar to produce. All that is needed to address the supply shortage is political will.”

While the study has some shortcomings – namely that it didn’t provide a breakdown of positive tests among COVID-19 participants – it does provide important insight for physicians, Sachin Gupta, MD, a pulmonary and critical care specialist in San Francisco, said in an interview. “The strength of a meta-analysis is that you’re able to get a composite idea; that’s one up side to this,” he said. “They’re confirming what we knew: that distance matters; that more protective masks reduce risk of infection; and that eye protection has an important role.”

Dr. Chu and colleagues have no relevant financial relationships to disclose. One member of SURGE is participating in a clinical trial comparing medical masks and N95 respirators. The World Health Organization provided partial funding for the study.

SOURCE: Chu DK et al. Lancet. 2020 Jun 2; doi.org/10.1016/ S0140-6736(20)31142-9 .

A study that claims to be the first review of all the available evidence of the effectiveness of physical distancing, face masks, and eye protection to prevent spread of COVID-19 and other respiratory diseases has quantified the effectiveness of these protective measures. The study found that greater physical distancing from an exposed person significantly reduces risk of transmission and that N95 masks, particularly for health care workers, are more effective than other face coverings.

The meta-analysis, published online in The Lancet (2020 Jun 2; doi.org/10.1016/ S0140-6736(20)31142-9) also marks the first evaluation of these protective measures in both community and health care settings for COVID-19, the study authors stated.

“The risk for infection is highly dependent on distance to the individual infected and the type of face mask and eye protection worn,” wrote Derek K. Chu, MD, PhD, of McMaster University in Hamilton, Ont., and colleagues, reporting on behalf of the COVID-19 Systematic Urgent Review Group Effort, or SURGE.

The study reported that physical distancing of at least 1 meter, or about a yard, “seems to be strongly associated with a large protective effect,” but that distancing of 2 meters or about 6 feet could be more effective.

The study involved a systematic review of 172 observational studies across six continents that evaluated distance measures, face masks, and eye protection to prevent transmission between patients with confirmed or probable COVID-19, other severe acute respiratory syndrome (SARS) disease, and Middle East respiratory syndrome (MERS), and their family members, caregivers and health care workers up to May 3, 2020. The meta-analysis involved pooled estimates from 44 comparative studies with 25,697 participants, including seven studies of COVID-19 with 6,674 participants. None of the studies included in the meta-analysis were randomized clinical trials.

A subanalysis of 29 unadjusted and 9 adjusted studies found that the absolute risk of infection in proximity to an exposed individual was 12.8% at 1 m and 2.6% at 2 m. The risk remained constant even when the six COVID-19 studies in this subanalysis were isolated and regardless of being in a health care or non–health-care setting. Each meter of increased distance resulted in a doubling in the change in relative risk (P = .041).

The study also identified what Dr. Chu and colleagues characterized as a “large reduction” in infection risk with the use of both N95 or similar respirators or face masks, with an adjusted risk of infection of 3.1% with a face covering vs. a 17.4% without. The researchers also found a stronger association in health care settings vs. non–health care settings, with a relative risk of 0.3 vs. 0.56, respectively (P = .049). The protective effect of N95 or similar respirators was greater than other masks, with adjusted odds ratios of 0.04 vs. 0.33 (P = .09).

Eye protection was found to reduce the risk of infection to 5.5% vs. 16% without eye protection.

The study also identified potential barriers to social distancing and use of masks and eye protection: discomfort, resource use “linked with potentially decreased equity,” less clear communication, and a perceived lack of empathy on the part of providers toward patients.

Dr. Chu and colleagues wrote that more “high-quality” research, including randomized trials of the optimal physical distance and evaluation of different mask types in non–health care settings “is urgently needed.” They added, “Policymakers at all levels should, therefore, strive to address equity implications for groups with currently limited access to face masks and eye protection.”

The goal of this study was to “inform WHO guidance documents,” the study noted. “Governments and the public health community can use our results to give clear advice for community settings and healthcare workers on these protective measures to reduce infection risk,” said study co-leader Holger Schünemann, MD, MSc, PhD, of McMaster University.

Prof. Raina MacIntyre, MBBS, PhD, head of the biosecurity research program at the Kirby Institute at the University of New South Wales in Sydney, who authored the comment that accompanied the article, said that this study provides evidence for stronger PPE guidelines.

“The Centers for Disease Control and Prevention initially recommended N95s for health workers treating COVID-19 patients, but later downgraded this to surgical masks and even cloth masks and bandannas when there was a supply shortage,” she said. “This study shows that N95s are superior masks and should prompt a review of guidelines that recommend anything less for health workers.”

Recommending anything less than N95 masks for health workers is like sending troops into battle “unarmed or with bows and arrows against a fully armed enemy,” she said. “We are not talking about a device that costs hundreds or thousands of dollars; a N95 costs less than a dollar to produce. All that is needed to address the supply shortage is political will.”

While the study has some shortcomings – namely that it didn’t provide a breakdown of positive tests among COVID-19 participants – it does provide important insight for physicians, Sachin Gupta, MD, a pulmonary and critical care specialist in San Francisco, said in an interview. “The strength of a meta-analysis is that you’re able to get a composite idea; that’s one up side to this,” he said. “They’re confirming what we knew: that distance matters; that more protective masks reduce risk of infection; and that eye protection has an important role.”

Dr. Chu and colleagues have no relevant financial relationships to disclose. One member of SURGE is participating in a clinical trial comparing medical masks and N95 respirators. The World Health Organization provided partial funding for the study.

SOURCE: Chu DK et al. Lancet. 2020 Jun 2; doi.org/10.1016/ S0140-6736(20)31142-9 .

A study that claims to be the first review of all the available evidence of the effectiveness of physical distancing, face masks, and eye protection to prevent spread of COVID-19 and other respiratory diseases has quantified the effectiveness of these protective measures. The study found that greater physical distancing from an exposed person significantly reduces risk of transmission and that N95 masks, particularly for health care workers, are more effective than other face coverings.

The meta-analysis, published online in The Lancet (2020 Jun 2; doi.org/10.1016/ S0140-6736(20)31142-9) also marks the first evaluation of these protective measures in both community and health care settings for COVID-19, the study authors stated.

“The risk for infection is highly dependent on distance to the individual infected and the type of face mask and eye protection worn,” wrote Derek K. Chu, MD, PhD, of McMaster University in Hamilton, Ont., and colleagues, reporting on behalf of the COVID-19 Systematic Urgent Review Group Effort, or SURGE.

The study reported that physical distancing of at least 1 meter, or about a yard, “seems to be strongly associated with a large protective effect,” but that distancing of 2 meters or about 6 feet could be more effective.

The study involved a systematic review of 172 observational studies across six continents that evaluated distance measures, face masks, and eye protection to prevent transmission between patients with confirmed or probable COVID-19, other severe acute respiratory syndrome (SARS) disease, and Middle East respiratory syndrome (MERS), and their family members, caregivers and health care workers up to May 3, 2020. The meta-analysis involved pooled estimates from 44 comparative studies with 25,697 participants, including seven studies of COVID-19 with 6,674 participants. None of the studies included in the meta-analysis were randomized clinical trials.

A subanalysis of 29 unadjusted and 9 adjusted studies found that the absolute risk of infection in proximity to an exposed individual was 12.8% at 1 m and 2.6% at 2 m. The risk remained constant even when the six COVID-19 studies in this subanalysis were isolated and regardless of being in a health care or non–health-care setting. Each meter of increased distance resulted in a doubling in the change in relative risk (P = .041).

The study also identified what Dr. Chu and colleagues characterized as a “large reduction” in infection risk with the use of both N95 or similar respirators or face masks, with an adjusted risk of infection of 3.1% with a face covering vs. a 17.4% without. The researchers also found a stronger association in health care settings vs. non–health care settings, with a relative risk of 0.3 vs. 0.56, respectively (P = .049). The protective effect of N95 or similar respirators was greater than other masks, with adjusted odds ratios of 0.04 vs. 0.33 (P = .09).

Eye protection was found to reduce the risk of infection to 5.5% vs. 16% without eye protection.

The study also identified potential barriers to social distancing and use of masks and eye protection: discomfort, resource use “linked with potentially decreased equity,” less clear communication, and a perceived lack of empathy on the part of providers toward patients.

Dr. Chu and colleagues wrote that more “high-quality” research, including randomized trials of the optimal physical distance and evaluation of different mask types in non–health care settings “is urgently needed.” They added, “Policymakers at all levels should, therefore, strive to address equity implications for groups with currently limited access to face masks and eye protection.”

The goal of this study was to “inform WHO guidance documents,” the study noted. “Governments and the public health community can use our results to give clear advice for community settings and healthcare workers on these protective measures to reduce infection risk,” said study co-leader Holger Schünemann, MD, MSc, PhD, of McMaster University.

Prof. Raina MacIntyre, MBBS, PhD, head of the biosecurity research program at the Kirby Institute at the University of New South Wales in Sydney, who authored the comment that accompanied the article, said that this study provides evidence for stronger PPE guidelines.

“The Centers for Disease Control and Prevention initially recommended N95s for health workers treating COVID-19 patients, but later downgraded this to surgical masks and even cloth masks and bandannas when there was a supply shortage,” she said. “This study shows that N95s are superior masks and should prompt a review of guidelines that recommend anything less for health workers.”

Recommending anything less than N95 masks for health workers is like sending troops into battle “unarmed or with bows and arrows against a fully armed enemy,” she said. “We are not talking about a device that costs hundreds or thousands of dollars; a N95 costs less than a dollar to produce. All that is needed to address the supply shortage is political will.”

While the study has some shortcomings – namely that it didn’t provide a breakdown of positive tests among COVID-19 participants – it does provide important insight for physicians, Sachin Gupta, MD, a pulmonary and critical care specialist in San Francisco, said in an interview. “The strength of a meta-analysis is that you’re able to get a composite idea; that’s one up side to this,” he said. “They’re confirming what we knew: that distance matters; that more protective masks reduce risk of infection; and that eye protection has an important role.”

Dr. Chu and colleagues have no relevant financial relationships to disclose. One member of SURGE is participating in a clinical trial comparing medical masks and N95 respirators. The World Health Organization provided partial funding for the study.

SOURCE: Chu DK et al. Lancet. 2020 Jun 2; doi.org/10.1016/ S0140-6736(20)31142-9 .

The Navajo people have dealt with adversity that has tested our strength and resilience since our creation. In Navajo culture, the Holy People or gods challenged us with Naayee (monsters). We endured and learned from each Naayee, hunger, and death to name a few adversities. The COVID-19 pandemic, or “Big Cough” (Dikos Nitsaa’igii -19 in Navajo language) is a monster confronting the Navajo today. It has had significant impact on our nation and people.

The Navajo have the most cases of the COVID-19 virus of any tribe in the United States, and numbers as of May 31, 2020, are 5,348, with 246 confirmed deaths.¹ The Navajo Nation, which once lagged behind New York, has reported the largest per-capita infection rate in the United States.

These devastating numbers, which might be leveling off, are associated with Navajo people having higher-than-average numbers of diabetes, heart disease, and cancer. This is compounded with 30%-40% of homes having no electricity or running water, and a poverty rate of about 38%.²

Geographical and cultural factors also contribute to the inability to gain a foothold in mitigating the number of cases. The Navajo Nation is the largest tribe in the United States, covering 27,000 square miles over an arid, red rock expanse with canyons and mountains. The population is over 250,000,³ and Navajo have traditionally lived in matrilineal clan units throughout the reservation, the size of West Virginia. The family traditional dwelling, called a “hogan,” often is clustered together. Multiple generations live together in these units. The COVID-19 virus inflicted many Navajo and rapidly spread to the elderly in these close-proximity living quarters.

Most Navajo live away from services and grocery stores and travel back and forth for food and water, which contributes to the virus rapidly being transmitted among the community members. Education aimed at curbing travel and spread of the virus was issued with curfews, commands to stay at home and keep social distance, and protect elders. The Navajo leadership and traditional medicine people, meanwhile, advised the people to follow their cultural values by caring for family and community members and providing a safe environment.
 

Resources are spread out

There are only 13 stores in this expansive reservation,⁴ so tribal members rely on traveling to border towns, such as Farmington and Gallup, N.M., Families usually travel to these towns on weekends to replenish food and supplies. There has been a cluster of cases in Gallup, N.M., so to reduce the numbers, the town shut itself off from outsiders – including the Navajo people coming to buy food, do laundry, and get water and feed for livestock. This has affected and stressed the Navajo further in attempting to access necessities.

Access to health care is already challenging because of lack of transportation and distance. This has made it more difficult to access COVID-19 testing and more challenging to get the results back. The Indian Health Service has been the designated health care system for the Navajo since 1955. The Treaty of Bosque Redondo, signed by the Navajo in 1868, included the provision of health care, as well as education in exchange for tracts of land, that included the Navajo homeland or Dinetah.⁵

The Indian Health Service provides care with hospitals and clinics throughout the reservation. Some of the IHS facilities have been taken over by the Navajo, so there are four Navajo tribally controlled hospitals, along with one private hospital. Coordination of care for a pandemic is, therefore, more challenging to coordinate. This contributes to problems with coordination of the health care, establishing alternate care sites, accessing personal protective equipment, and providing testing sites. The Navajo Nation Council is working hard to equitably distribute the $600 million from the CARES Act.⁶

Dealing with the pandemic is compromised by chronic underfunding from the U.S. government. The treaty obligation of the U.S. government is to provide health care to all federally recognized Native Americans. The IHS, which has been designated to provide that care for a tribal person, gets one-third the Medicare dollars for health care provided for a person in the general population.⁷ Health factors have led to the public health issues of poorly controlled diabetes, obesity, and coronary artery disease, which is related to this underfunding and the high rate of COVID-19 cases. Parts of the reservation are also exposed to high levels of pollution from oil and gas wells from the coal-fueled power plants. Those exposed to these high levels of pollutions have a higher than average number of cases of COVID-19, higher than in areas where the pollution is markedly lower.⁸

The Navajo are having to rely on the strength and resilience of traditional Navajo culture and philosophy to confront this monster, Dikos Nitsaa’igii’ 19. We have relied on Western medicine and its limited resources but now need to empower the strength from our traditional ways of knowing. We have used this knowledge in times of adversity for hundreds of years. The Navajo elders and medicine people have reminded us we have dealt with monsters and know how to endure hardship and be resilient. This helps to ameliorate mental health conditions, but there are still issues that remain challenging.

Those having the virus go through times of shortness of breath, which produces anxiety and panic. The risk of death adds further stress, and for a family-oriented culture, the need to isolate from family adds further stress. For the elderly and young people with more serious disease having to go to the hospital alone without family, often far from home, is so challenging. Connecting family by phone or social media with those stricken is essential to decrease anxiety and isolation. Those infected with the virus can learn breathing exercises, which can help the damage from the virus and decrease emotional activation and triggers. Specific breathing techniques can be taught by medical providers. An effective breathing technique to reduce anxiety is coherent breathing, which is done by inhaling 6 seconds and exhaling for 6 seconds without holding your breath. Behavioral health practitioners are available in the tribal and IHS mental health clinics to refer patients to therapy support to manage anxiety and are available by telemedicine. Many of these programs are offering social media informational sessions for the Navajo community. Navajo people often access traditional healing for protection prayers and ceremonies. Some of the tribal and IHS programs provide traditional counselors to talk to. The Navajo access healing that focuses on restoring balance to the body, mind, and spirit.

Taking action against the virus by social distancing, hand washing, and wearing masks can go a long way in reducing anxiety and fear about getting the virus. Resources to help the Navajo Nation are coming from all over the world, from as far as Ireland,⁹ Doctors Without Borders, ¹⁰ and University of San Francisco.¹¹

Two resources that provide relief on the reservation are the Navajo Relief Fund and United Natives.
 

References

1. Navaho Times. 2020 May 27.

2. Ingalls A et al. BMC Obes. 2019 May 6. doi: 10.1186/s40608-019-0233-9.

3. U.S. Census 2010, as reported by discovernavajo.com.

4. Gould C et al. “Addressing food insecurity on the Navajo reservation through sustainable greenhouses.” 2018 Aug.

5. Native Knowledge 360. Smithsonian Institution. “Bosque Redondo.”

6. Personal communication, Carl Roessel Slater, Navajo Nation Council delegate.

7. IHS Profile Fact Sheet.

8. Wu X et al. medRxiv. 2020 Apr 27.

9. Carroll R. ”Irish support for Native American COVID-19 relief highlights historic bond.” The Guardian. 2020 May 9.

10. Capatides C. “Doctors Without Borders dispatches team to the Navajo Nation” CBS News. 2020 May 11.

11. Weiler N. “UCSF sends second wave of health workers to Navajo Nation.” UCSF.edu. 2020 May 21.
 

Dr. Roessel is a Navajo board-certified psychiatrist practicing in Santa Fe, N.M., working with the local indigenous population. She has special expertise in cultural psychiatry; her childhood was spent growing up in the Navajo Nation with her grandfather, who was a Navajo medicine man. Her psychiatric practice focuses on integrating indigenous knowledge and principles. Dr. Roessel is a distinguished fellow of the American Psychiatric Association. She has no disclosures.

The Navajo people have dealt with adversity that has tested our strength and resilience since our creation. In Navajo culture, the Holy People or gods challenged us with Naayee (monsters). We endured and learned from each Naayee, hunger, and death to name a few adversities. The COVID-19 pandemic, or “Big Cough” (Dikos Nitsaa’igii -19 in Navajo language) is a monster confronting the Navajo today. It has had significant impact on our nation and people.

The Navajo have the most cases of the COVID-19 virus of any tribe in the United States, and numbers as of May 31, 2020, are 5,348, with 246 confirmed deaths.¹ The Navajo Nation, which once lagged behind New York, has reported the largest per-capita infection rate in the United States.

These devastating numbers, which might be leveling off, are associated with Navajo people having higher-than-average numbers of diabetes, heart disease, and cancer. This is compounded with 30%-40% of homes having no electricity or running water, and a poverty rate of about 38%.²

Geographical and cultural factors also contribute to the inability to gain a foothold in mitigating the number of cases. The Navajo Nation is the largest tribe in the United States, covering 27,000 square miles over an arid, red rock expanse with canyons and mountains. The population is over 250,000,³ and Navajo have traditionally lived in matrilineal clan units throughout the reservation, the size of West Virginia. The family traditional dwelling, called a “hogan,” often is clustered together. Multiple generations live together in these units. The COVID-19 virus inflicted many Navajo and rapidly spread to the elderly in these close-proximity living quarters.

Most Navajo live away from services and grocery stores and travel back and forth for food and water, which contributes to the virus rapidly being transmitted among the community members. Education aimed at curbing travel and spread of the virus was issued with curfews, commands to stay at home and keep social distance, and protect elders. The Navajo leadership and traditional medicine people, meanwhile, advised the people to follow their cultural values by caring for family and community members and providing a safe environment.
 

Resources are spread out

There are only 13 stores in this expansive reservation,⁴ so tribal members rely on traveling to border towns, such as Farmington and Gallup, N.M., Families usually travel to these towns on weekends to replenish food and supplies. There has been a cluster of cases in Gallup, N.M., so to reduce the numbers, the town shut itself off from outsiders – including the Navajo people coming to buy food, do laundry, and get water and feed for livestock. This has affected and stressed the Navajo further in attempting to access necessities.

Access to health care is already challenging because of lack of transportation and distance. This has made it more difficult to access COVID-19 testing and more challenging to get the results back. The Indian Health Service has been the designated health care system for the Navajo since 1955. The Treaty of Bosque Redondo, signed by the Navajo in 1868, included the provision of health care, as well as education in exchange for tracts of land, that included the Navajo homeland or Dinetah.⁵

The Indian Health Service provides care with hospitals and clinics throughout the reservation. Some of the IHS facilities have been taken over by the Navajo, so there are four Navajo tribally controlled hospitals, along with one private hospital. Coordination of care for a pandemic is, therefore, more challenging to coordinate. This contributes to problems with coordination of the health care, establishing alternate care sites, accessing personal protective equipment, and providing testing sites. The Navajo Nation Council is working hard to equitably distribute the $600 million from the CARES Act.⁶

Dealing with the pandemic is compromised by chronic underfunding from the U.S. government. The treaty obligation of the U.S. government is to provide health care to all federally recognized Native Americans. The IHS, which has been designated to provide that care for a tribal person, gets one-third the Medicare dollars for health care provided for a person in the general population.⁷ Health factors have led to the public health issues of poorly controlled diabetes, obesity, and coronary artery disease, which is related to this underfunding and the high rate of COVID-19 cases. Parts of the reservation are also exposed to high levels of pollution from oil and gas wells from the coal-fueled power plants. Those exposed to these high levels of pollutions have a higher than average number of cases of COVID-19, higher than in areas where the pollution is markedly lower.⁸

The Navajo are having to rely on the strength and resilience of traditional Navajo culture and philosophy to confront this monster, Dikos Nitsaa’igii’ 19. We have relied on Western medicine and its limited resources but now need to empower the strength from our traditional ways of knowing. We have used this knowledge in times of adversity for hundreds of years. The Navajo elders and medicine people have reminded us we have dealt with monsters and know how to endure hardship and be resilient. This helps to ameliorate mental health conditions, but there are still issues that remain challenging.

Those having the virus go through times of shortness of breath, which produces anxiety and panic. The risk of death adds further stress, and for a family-oriented culture, the need to isolate from family adds further stress. For the elderly and young people with more serious disease having to go to the hospital alone without family, often far from home, is so challenging. Connecting family by phone or social media with those stricken is essential to decrease anxiety and isolation. Those infected with the virus can learn breathing exercises, which can help the damage from the virus and decrease emotional activation and triggers. Specific breathing techniques can be taught by medical providers. An effective breathing technique to reduce anxiety is coherent breathing, which is done by inhaling 6 seconds and exhaling for 6 seconds without holding your breath. Behavioral health practitioners are available in the tribal and IHS mental health clinics to refer patients to therapy support to manage anxiety and are available by telemedicine. Many of these programs are offering social media informational sessions for the Navajo community. Navajo people often access traditional healing for protection prayers and ceremonies. Some of the tribal and IHS programs provide traditional counselors to talk to. The Navajo access healing that focuses on restoring balance to the body, mind, and spirit.

Taking action against the virus by social distancing, hand washing, and wearing masks can go a long way in reducing anxiety and fear about getting the virus. Resources to help the Navajo Nation are coming from all over the world, from as far as Ireland,⁹ Doctors Without Borders, ¹⁰ and University of San Francisco.¹¹

Two resources that provide relief on the reservation are the Navajo Relief Fund and United Natives.
 

References

1. Navaho Times. 2020 May 27.

2. Ingalls A et al. BMC Obes. 2019 May 6. doi: 10.1186/s40608-019-0233-9.

3. U.S. Census 2010, as reported by discovernavajo.com.

4. Gould C et al. “Addressing food insecurity on the Navajo reservation through sustainable greenhouses.” 2018 Aug.

5. Native Knowledge 360. Smithsonian Institution. “Bosque Redondo.”

6. Personal communication, Carl Roessel Slater, Navajo Nation Council delegate.

7. IHS Profile Fact Sheet.

8. Wu X et al. medRxiv. 2020 Apr 27.

9. Carroll R. ”Irish support for Native American COVID-19 relief highlights historic bond.” The Guardian. 2020 May 9.

10. Capatides C. “Doctors Without Borders dispatches team to the Navajo Nation” CBS News. 2020 May 11.

11. Weiler N. “UCSF sends second wave of health workers to Navajo Nation.” UCSF.edu. 2020 May 21.
 

Dr. Roessel is a Navajo board-certified psychiatrist practicing in Santa Fe, N.M., working with the local indigenous population. She has special expertise in cultural psychiatry; her childhood was spent growing up in the Navajo Nation with her grandfather, who was a Navajo medicine man. Her psychiatric practice focuses on integrating indigenous knowledge and principles. Dr. Roessel is a distinguished fellow of the American Psychiatric Association. She has no disclosures.

The Navajo people have dealt with adversity that has tested our strength and resilience since our creation. In Navajo culture, the Holy People or gods challenged us with Naayee (monsters). We endured and learned from each Naayee, hunger, and death to name a few adversities. The COVID-19 pandemic, or “Big Cough” (Dikos Nitsaa’igii -19 in Navajo language) is a monster confronting the Navajo today. It has had significant impact on our nation and people.

The Navajo have the most cases of the COVID-19 virus of any tribe in the United States, and numbers as of May 31, 2020, are 5,348, with 246 confirmed deaths.¹ The Navajo Nation, which once lagged behind New York, has reported the largest per-capita infection rate in the United States.

These devastating numbers, which might be leveling off, are associated with Navajo people having higher-than-average numbers of diabetes, heart disease, and cancer. This is compounded with 30%-40% of homes having no electricity or running water, and a poverty rate of about 38%.²

Geographical and cultural factors also contribute to the inability to gain a foothold in mitigating the number of cases. The Navajo Nation is the largest tribe in the United States, covering 27,000 square miles over an arid, red rock expanse with canyons and mountains. The population is over 250,000,³ and Navajo have traditionally lived in matrilineal clan units throughout the reservation, the size of West Virginia. The family traditional dwelling, called a “hogan,” often is clustered together. Multiple generations live together in these units. The COVID-19 virus inflicted many Navajo and rapidly spread to the elderly in these close-proximity living quarters.

Most Navajo live away from services and grocery stores and travel back and forth for food and water, which contributes to the virus rapidly being transmitted among the community members. Education aimed at curbing travel and spread of the virus was issued with curfews, commands to stay at home and keep social distance, and protect elders. The Navajo leadership and traditional medicine people, meanwhile, advised the people to follow their cultural values by caring for family and community members and providing a safe environment.
 

Resources are spread out

There are only 13 stores in this expansive reservation,⁴ so tribal members rely on traveling to border towns, such as Farmington and Gallup, N.M., Families usually travel to these towns on weekends to replenish food and supplies. There has been a cluster of cases in Gallup, N.M., so to reduce the numbers, the town shut itself off from outsiders – including the Navajo people coming to buy food, do laundry, and get water and feed for livestock. This has affected and stressed the Navajo further in attempting to access necessities.

Access to health care is already challenging because of lack of transportation and distance. This has made it more difficult to access COVID-19 testing and more challenging to get the results back. The Indian Health Service has been the designated health care system for the Navajo since 1955. The Treaty of Bosque Redondo, signed by the Navajo in 1868, included the provision of health care, as well as education in exchange for tracts of land, that included the Navajo homeland or Dinetah.⁵

The Indian Health Service provides care with hospitals and clinics throughout the reservation. Some of the IHS facilities have been taken over by the Navajo, so there are four Navajo tribally controlled hospitals, along with one private hospital. Coordination of care for a pandemic is, therefore, more challenging to coordinate. This contributes to problems with coordination of the health care, establishing alternate care sites, accessing personal protective equipment, and providing testing sites. The Navajo Nation Council is working hard to equitably distribute the $600 million from the CARES Act.⁶

Dealing with the pandemic is compromised by chronic underfunding from the U.S. government. The treaty obligation of the U.S. government is to provide health care to all federally recognized Native Americans. The IHS, which has been designated to provide that care for a tribal person, gets one-third the Medicare dollars for health care provided for a person in the general population.⁷ Health factors have led to the public health issues of poorly controlled diabetes, obesity, and coronary artery disease, which is related to this underfunding and the high rate of COVID-19 cases. Parts of the reservation are also exposed to high levels of pollution from oil and gas wells from the coal-fueled power plants. Those exposed to these high levels of pollutions have a higher than average number of cases of COVID-19, higher than in areas where the pollution is markedly lower.⁸

The Navajo are having to rely on the strength and resilience of traditional Navajo culture and philosophy to confront this monster, Dikos Nitsaa’igii’ 19. We have relied on Western medicine and its limited resources but now need to empower the strength from our traditional ways of knowing. We have used this knowledge in times of adversity for hundreds of years. The Navajo elders and medicine people have reminded us we have dealt with monsters and know how to endure hardship and be resilient. This helps to ameliorate mental health conditions, but there are still issues that remain challenging.

Those having the virus go through times of shortness of breath, which produces anxiety and panic. The risk of death adds further stress, and for a family-oriented culture, the need to isolate from family adds further stress. For the elderly and young people with more serious disease having to go to the hospital alone without family, often far from home, is so challenging. Connecting family by phone or social media with those stricken is essential to decrease anxiety and isolation. Those infected with the virus can learn breathing exercises, which can help the damage from the virus and decrease emotional activation and triggers. Specific breathing techniques can be taught by medical providers. An effective breathing technique to reduce anxiety is coherent breathing, which is done by inhaling 6 seconds and exhaling for 6 seconds without holding your breath. Behavioral health practitioners are available in the tribal and IHS mental health clinics to refer patients to therapy support to manage anxiety and are available by telemedicine. Many of these programs are offering social media informational sessions for the Navajo community. Navajo people often access traditional healing for protection prayers and ceremonies. Some of the tribal and IHS programs provide traditional counselors to talk to. The Navajo access healing that focuses on restoring balance to the body, mind, and spirit.

Taking action against the virus by social distancing, hand washing, and wearing masks can go a long way in reducing anxiety and fear about getting the virus. Resources to help the Navajo Nation are coming from all over the world, from as far as Ireland,⁹ Doctors Without Borders, ¹⁰ and University of San Francisco.¹¹

Two resources that provide relief on the reservation are the Navajo Relief Fund and United Natives.
 

References

1. Navaho Times. 2020 May 27.

2. Ingalls A et al. BMC Obes. 2019 May 6. doi: 10.1186/s40608-019-0233-9.

3. U.S. Census 2010, as reported by discovernavajo.com.

4. Gould C et al. “Addressing food insecurity on the Navajo reservation through sustainable greenhouses.” 2018 Aug.

5. Native Knowledge 360. Smithsonian Institution. “Bosque Redondo.”

6. Personal communication, Carl Roessel Slater, Navajo Nation Council delegate.

7. IHS Profile Fact Sheet.

8. Wu X et al. medRxiv. 2020 Apr 27.

9. Carroll R. ”Irish support for Native American COVID-19 relief highlights historic bond.” The Guardian. 2020 May 9.

10. Capatides C. “Doctors Without Borders dispatches team to the Navajo Nation” CBS News. 2020 May 11.

11. Weiler N. “UCSF sends second wave of health workers to Navajo Nation.” UCSF.edu. 2020 May 21.
 

Dr. Roessel is a Navajo board-certified psychiatrist practicing in Santa Fe, N.M., working with the local indigenous population. She has special expertise in cultural psychiatry; her childhood was spent growing up in the Navajo Nation with her grandfather, who was a Navajo medicine man. Her psychiatric practice focuses on integrating indigenous knowledge and principles. Dr. Roessel is a distinguished fellow of the American Psychiatric Association. She has no disclosures.

Here are the stories our MDedge editors across specialties think you need to know about today:

Mass protests could cause COVID-19 outbreaks

As mass protests continue throughout the country, officials expressed concern about a potential spike in coronavirus cases in the coming days.

“There’s going to be a lot of issues coming out of what’s happened in the last week, but one of them is going to be that chains of transmission will have become lit from these gatherings,” Scott Gottlieb, former FDA commissioner, said on the CBS News show “Face the Nation.”

The protests generally have started peacefully with some demonstrators following physical distancing rules. But they have evolved into sometimes violent gatherings of hundreds or thousands of people where standing six feet apart is impossible. Chanting, singing, and shouting may spread the virus through respiratory droplets.

“If you were out protesting last night, you probably need to go get a COVID test this week,” Atlanta Mayor Keisha Lance Bottoms said Saturday, according to The Associated Press. Read More.
 

Diabetes: 1 in 10 hospitalized for COVID-19 die within a week

More than 10% of people with diabetes who are hospitalized for COVID-19 die within a week, while nearly a third require mechanical ventilation, new research shows.

Data from the CORONADO study also revealed that body mass index was independently associated with death or intubation at 7 days, while A_1c and use of renin-angiotensin-aldosterone system blockers and dipeptidyl peptidase–4 inhibitors were not.

The presence of diabetes-related complications and older age also increased the risk of death.

The findings were published online in Diabetologia.

Previous studies have linked diabetes to worse outcomes in COVID-19, but this is the first to examine specific characteristics before and at the time of hospital admission that predict worse outcomes among people with diabetes, study coauthor Samy Hadjadj, MD, PhD, said in an interview. Read more.
 

Most adult epilepsy-related deaths could be avoided

Almost 80% of epilepsy deaths among adults are potentially avoidable, results of a new study suggest.

The research shows that such avoidable deaths “remain common and have not declined over time, despite advances in treatment,” Gashirai Mbizvo, MBChB, PhD, of the University of Edinburgh, United Kingdom, said during a press briefing. The findings were presented at the virtual/online Congress of the European Academy of Neurology (EAN) 2020.

Dr. Mbizvo investigated adolescents and adults aged 16 years and older who died because of epilepsy from 2009 to 2016. He compared this group to patients of similar age who were living with epilepsy. A total of 2149 epilepsy-related deaths occurred.

The most common cause of death in the 16- to 54-year age group was sudden unexpected death in epilepsy, followed by respiratory disorders, such as aspiration pneumonia. “We think this should be avoidable, in the sense that these are people that could perhaps be targeted early with, for example, antibiotics,” Dr. Mbizvo said.

The next most common cause of death was circulatory disease, largely cardiac arrest.

“The idea is that electroexcitation – an abnormality in the brain – and the heart are related, and maybe that’s translating to a risk of death,” Dr. Mbizvo said. Read More.
 

FDA approves combo treatment for hepatocellular cancer

The Food and Drug Administration has approved atezolizumab (Tecentriq) in combination with bevacizumab (Avastin) to treat patients with unresectable or metastatic hepatocellular carcinoma who have not received prior systemic therapy.

The approval was supported by results from the IMbrave150 trial (N Engl J Med 2020; 382:1894-1905). This phase 3 trial enrolled 501 patients with hepatocellular carcinoma who were randomized to receive either sorafenib or atezolizumab plus bevacizumab.

The median overall survival was not reached in patients who received atezolizumab plus bevacizumab, but it was 13.2 months in patients who received sorafenib.

The median progression-free survival was 6.8 months in patients who received atezolizumab plus bevacizumab and 4.3 months for those who received sorafenib. Read more.
 

For more on COVID-19, visit our Resource Center. All of our latest news is available on MDedge.com.

Here are the stories our MDedge editors across specialties think you need to know about today:

Mass protests could cause COVID-19 outbreaks

As mass protests continue throughout the country, officials expressed concern about a potential spike in coronavirus cases in the coming days.

“There’s going to be a lot of issues coming out of what’s happened in the last week, but one of them is going to be that chains of transmission will have become lit from these gatherings,” Scott Gottlieb, former FDA commissioner, said on the CBS News show “Face the Nation.”

The protests generally have started peacefully with some demonstrators following physical distancing rules. But they have evolved into sometimes violent gatherings of hundreds or thousands of people where standing six feet apart is impossible. Chanting, singing, and shouting may spread the virus through respiratory droplets.

“If you were out protesting last night, you probably need to go get a COVID test this week,” Atlanta Mayor Keisha Lance Bottoms said Saturday, according to The Associated Press. Read More.
 

Diabetes: 1 in 10 hospitalized for COVID-19 die within a week

More than 10% of people with diabetes who are hospitalized for COVID-19 die within a week, while nearly a third require mechanical ventilation, new research shows.

Data from the CORONADO study also revealed that body mass index was independently associated with death or intubation at 7 days, while A_1c and use of renin-angiotensin-aldosterone system blockers and dipeptidyl peptidase–4 inhibitors were not.

The presence of diabetes-related complications and older age also increased the risk of death.

The findings were published online in Diabetologia.

Previous studies have linked diabetes to worse outcomes in COVID-19, but this is the first to examine specific characteristics before and at the time of hospital admission that predict worse outcomes among people with diabetes, study coauthor Samy Hadjadj, MD, PhD, said in an interview. Read more.
 

Most adult epilepsy-related deaths could be avoided

Almost 80% of epilepsy deaths among adults are potentially avoidable, results of a new study suggest.

The research shows that such avoidable deaths “remain common and have not declined over time, despite advances in treatment,” Gashirai Mbizvo, MBChB, PhD, of the University of Edinburgh, United Kingdom, said during a press briefing. The findings were presented at the virtual/online Congress of the European Academy of Neurology (EAN) 2020.

Dr. Mbizvo investigated adolescents and adults aged 16 years and older who died because of epilepsy from 2009 to 2016. He compared this group to patients of similar age who were living with epilepsy. A total of 2149 epilepsy-related deaths occurred.

The most common cause of death in the 16- to 54-year age group was sudden unexpected death in epilepsy, followed by respiratory disorders, such as aspiration pneumonia. “We think this should be avoidable, in the sense that these are people that could perhaps be targeted early with, for example, antibiotics,” Dr. Mbizvo said.

The next most common cause of death was circulatory disease, largely cardiac arrest.

“The idea is that electroexcitation – an abnormality in the brain – and the heart are related, and maybe that’s translating to a risk of death,” Dr. Mbizvo said. Read More.
 

FDA approves combo treatment for hepatocellular cancer

The Food and Drug Administration has approved atezolizumab (Tecentriq) in combination with bevacizumab (Avastin) to treat patients with unresectable or metastatic hepatocellular carcinoma who have not received prior systemic therapy.

The approval was supported by results from the IMbrave150 trial (N Engl J Med 2020; 382:1894-1905). This phase 3 trial enrolled 501 patients with hepatocellular carcinoma who were randomized to receive either sorafenib or atezolizumab plus bevacizumab.

The median overall survival was not reached in patients who received atezolizumab plus bevacizumab, but it was 13.2 months in patients who received sorafenib.

The median progression-free survival was 6.8 months in patients who received atezolizumab plus bevacizumab and 4.3 months for those who received sorafenib. Read more.
 

For more on COVID-19, visit our Resource Center. All of our latest news is available on MDedge.com.

Here are the stories our MDedge editors across specialties think you need to know about today:

Mass protests could cause COVID-19 outbreaks

As mass protests continue throughout the country, officials expressed concern about a potential spike in coronavirus cases in the coming days.

“There’s going to be a lot of issues coming out of what’s happened in the last week, but one of them is going to be that chains of transmission will have become lit from these gatherings,” Scott Gottlieb, former FDA commissioner, said on the CBS News show “Face the Nation.”

The protests generally have started peacefully with some demonstrators following physical distancing rules. But they have evolved into sometimes violent gatherings of hundreds or thousands of people where standing six feet apart is impossible. Chanting, singing, and shouting may spread the virus through respiratory droplets.

“If you were out protesting last night, you probably need to go get a COVID test this week,” Atlanta Mayor Keisha Lance Bottoms said Saturday, according to The Associated Press. Read More.
 

Diabetes: 1 in 10 hospitalized for COVID-19 die within a week

More than 10% of people with diabetes who are hospitalized for COVID-19 die within a week, while nearly a third require mechanical ventilation, new research shows.

Data from the CORONADO study also revealed that body mass index was independently associated with death or intubation at 7 days, while A_1c and use of renin-angiotensin-aldosterone system blockers and dipeptidyl peptidase–4 inhibitors were not.

The presence of diabetes-related complications and older age also increased the risk of death.

The findings were published online in Diabetologia.

Previous studies have linked diabetes to worse outcomes in COVID-19, but this is the first to examine specific characteristics before and at the time of hospital admission that predict worse outcomes among people with diabetes, study coauthor Samy Hadjadj, MD, PhD, said in an interview. Read more.
 

Most adult epilepsy-related deaths could be avoided

Almost 80% of epilepsy deaths among adults are potentially avoidable, results of a new study suggest.

The research shows that such avoidable deaths “remain common and have not declined over time, despite advances in treatment,” Gashirai Mbizvo, MBChB, PhD, of the University of Edinburgh, United Kingdom, said during a press briefing. The findings were presented at the virtual/online Congress of the European Academy of Neurology (EAN) 2020.

Dr. Mbizvo investigated adolescents and adults aged 16 years and older who died because of epilepsy from 2009 to 2016. He compared this group to patients of similar age who were living with epilepsy. A total of 2149 epilepsy-related deaths occurred.

The most common cause of death in the 16- to 54-year age group was sudden unexpected death in epilepsy, followed by respiratory disorders, such as aspiration pneumonia. “We think this should be avoidable, in the sense that these are people that could perhaps be targeted early with, for example, antibiotics,” Dr. Mbizvo said.

The next most common cause of death was circulatory disease, largely cardiac arrest.

“The idea is that electroexcitation – an abnormality in the brain – and the heart are related, and maybe that’s translating to a risk of death,” Dr. Mbizvo said. Read More.
 

FDA approves combo treatment for hepatocellular cancer

The Food and Drug Administration has approved atezolizumab (Tecentriq) in combination with bevacizumab (Avastin) to treat patients with unresectable or metastatic hepatocellular carcinoma who have not received prior systemic therapy.

The approval was supported by results from the IMbrave150 trial (N Engl J Med 2020; 382:1894-1905). This phase 3 trial enrolled 501 patients with hepatocellular carcinoma who were randomized to receive either sorafenib or atezolizumab plus bevacizumab.

The median overall survival was not reached in patients who received atezolizumab plus bevacizumab, but it was 13.2 months in patients who received sorafenib.

The median progression-free survival was 6.8 months in patients who received atezolizumab plus bevacizumab and 4.3 months for those who received sorafenib. Read more.
 

For more on COVID-19, visit our Resource Center. All of our latest news is available on MDedge.com.

More than 1 in 10 people with diabetes hospitalized with COVID-19 die within a week, while nearly a third require mechanical ventilation, new research shows.

Data from the CORONADO (French Coronavirus SARS-CoV-2 and Diabetes Outcomes) study also revealed that body mass index (BMI) was independently associated with death or intubation at 7 days, while A_1c and use of renin-angiotensin-aldosterone system (RAAS) blockers and dipeptidyl peptidase–4 inhibitors were not.

The presence of diabetes-related complications and older age also increased the risk of death.

The findings were published online Diabetologia by Bertrand Cariou, MD, PhD, of the department of endocrinology at the Hôpital Guillaume et René Laennec in Nantes, France, and colleagues.
 

First study to examine specific characteristics at time of admission

Previous studies have linked diabetes to worse outcomes in COVID-19, but this is the first to examine specific characteristics before and at the time of hospital admission that predict worse outcomes among people with diabetes, study coauthor Samy Hadjadj, MD, PhD, said in an interview.

“Before the CORONADO study it was ‘all diabetes [patients] are the same.’ Now we can surely consider more precisely the risk, taking age, sex, BMI, complications, and [obstructive sleep apnea] as clear ‘very high-risk situations,’” said Dr. Hadjadj, of the same institution as Dr. Cariou.

Another clinical message, Dr. Hadjadj said, is that, “even in diabetes, each increase in BMI is associated with an increase in the risk of intubation and/or death in the 7 days following admission for COVID-19. So let’s target this population as a really important population to keep social distancing and stay alert on avoiding the virus.”

But he urged caution regarding the A_1c finding. “A_1c might be associated with admission to hospital but other factors far beyond A_1c drive the prognosis as soon as a patient is admitted. It’s surprising but reasonable speculation can explain this.”

And Dr. Hadjadj said that no obvious signals were identified with regard to medication use.

“Insulin is not suspected of having adverse effects closely related to COVID-19. RAAS blockers are not deleterious but indicative of hypertension, which is a comorbidity even in diabetes patients,” he said. (None of the patients studied were taking sodium-glucose cotransporter 2 inhibitors or glucagonlike peptide receptor agonists.)
 

_{Yet again, high BMI emerges as a major risk factor}

The study included 1,317 patients with diabetes and confirmed COVID-19 admitted to 53 French hospitals during March 10-31, 2020. Participants included 88.5% with type 2 diabetes, 3% with type 1 diabetes, and 3.1% newly diagnosed on admission. Mean age was 69.8 years.

Diabetes-related disorders on admission were reported in 11.1% of participants overall. These included 132 episodes of severe hyperglycemia, including 40 of ketosis, of which 19 were ketoacidosis, and 14 hypoglycemic events. Severe anorexia was reported in 6.3%.

The composite primary endpoint, tracheal intubation for mechanical ventilation and/or death within 7 days of admission, occurred in 29% of patients (n = 382).

Of the secondary outcomes, 31.1% (n = 410) were admitted to ICUs within 7 days of hospital admission, including 20.3% (n = 267) who required tracheal intubation for mechanical ventilation.

On day 7, 10.6% (n = 140) had died and 18.0% (n = 237) were discharged.

In the univariate analysis, the primary outcome was more frequent in men (69.1% vs. 63.2%; P = .0420) and those taking RAAS blockers (61.5% vs. 55.3%; P = .0386). Median BMI was significantly higher in those in whom the primary outcome occurred (29.1 vs 28.1 kg/m²; P = .0009),

Other characteristics prior to admission associated with risk of death on day 7 included age, hypertension, micro- and macrovascular diabetes-related complications, and comorbidities such as heart failure and treated obstructive sleep apnea.

Over 40% of those admitted had such complications. Of the patients analyzed, microvascular complications (eye, kidney, and neuropathy) were present in 47% and macrovascular complications (arteries of the heart, brain, and legs) were present in 41%.

Encouragingly, there were no deaths in patients aged under 65 years with type 1 diabetes, but only 39 participants had type 1 diabetes. Other work is ongoing to establish the effect of COVID-19 in this specific population, the researchers wrote.

Among prior medications, metformin use was lower in people who died, while insulin use, RAAS blockers, beta-blockers, loop diuretics, and mineralocorticoid-receptor antagonists were associated with death on day 7. The medication findings didn’t reach statistical significance, however.

When asked about the hint of a protective effect of metformin (odds ratio, 0.80; P = .4532), given that some experts have advised stopping it in the setting of COVID-19 because of the risk of lactic acidosis, Dr. Hadjadj said he wouldn’t necessarily stop it in all patients with COVID-19, but said, “let’s stop it in cases of severe condition.”
 

Analysis ongoing, ‘some new messages might pop up’

After adjustment for age and sex, BMI was significantly and positively associated with the primary outcome (P = .0001) but not with death on day 7 (P = .1488), and A_1c wasn’t associated with either outcome.

In a multivariable analysis that included characteristics prior to admission, BMI remained the only independent preadmission predictor associated with the primary outcome (adjusted odds ratio, 1.28), while factors independently associated with risk of death on day 7 included age, diabetes complication history, and treated obstructive sleep apnea.

And after adjustment for age and sex, admission plasma glucose level was significantly and positively associated with both the primary outcome (P = .0001) and death on day 7 (P = .0059).

In the multivariate analysis, admission characteristics that predicted the primary outcome were dyspnea, lymphopenia, increased AST, and increased C-reactive protein.

Dr. Hadjadj said his team is now “focusing on specific risk factors such as obesity, age, vascular complications, medications ... to perform some deeper analyses.”

“We look forward to analyzing the data on in-hospital stay up to day 28 after admission. Some new messages might well pop up,” he added.

But in the meantime, “Elderly populations with long-term diabetes with advanced diabetes-related complications and/or treated obstructive sleep apnea were particularly at risk of early death and might require specific management to avoid infection with the novel coronavirus,” the researchers stressed.

The study received funding from the Fondation Francophone de Recherche sur le Diabète and was supported by Novo Nordisk, MSD, Abbott, AstraZeneca, Lilly, and the Fédération Française des Diabétiques; Société Francophone du Diabète; and Air Liquide Healthcare International. Dr. Hadjadj reported receiving grants, personal fees, and/or nonfinancial support from AstraZeneca, Bayer, Boehringer Ingelheim, Dinno Santé, Eli Lilly, LVL, MSD, Novartis, Pierre Fabre Santé, Sanofi, Servier, and Valbiotis.

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

More than 1 in 10 people with diabetes hospitalized with COVID-19 die within a week, while nearly a third require mechanical ventilation, new research shows.

Data from the CORONADO (French Coronavirus SARS-CoV-2 and Diabetes Outcomes) study also revealed that body mass index (BMI) was independently associated with death or intubation at 7 days, while A_1c and use of renin-angiotensin-aldosterone system (RAAS) blockers and dipeptidyl peptidase–4 inhibitors were not.

The presence of diabetes-related complications and older age also increased the risk of death.

The findings were published online Diabetologia by Bertrand Cariou, MD, PhD, of the department of endocrinology at the Hôpital Guillaume et René Laennec in Nantes, France, and colleagues.
 

First study to examine specific characteristics at time of admission

Previous studies have linked diabetes to worse outcomes in COVID-19, but this is the first to examine specific characteristics before and at the time of hospital admission that predict worse outcomes among people with diabetes, study coauthor Samy Hadjadj, MD, PhD, said in an interview.

“Before the CORONADO study it was ‘all diabetes [patients] are the same.’ Now we can surely consider more precisely the risk, taking age, sex, BMI, complications, and [obstructive sleep apnea] as clear ‘very high-risk situations,’” said Dr. Hadjadj, of the same institution as Dr. Cariou.

Another clinical message, Dr. Hadjadj said, is that, “even in diabetes, each increase in BMI is associated with an increase in the risk of intubation and/or death in the 7 days following admission for COVID-19. So let’s target this population as a really important population to keep social distancing and stay alert on avoiding the virus.”

But he urged caution regarding the A_1c finding. “A_1c might be associated with admission to hospital but other factors far beyond A_1c drive the prognosis as soon as a patient is admitted. It’s surprising but reasonable speculation can explain this.”

And Dr. Hadjadj said that no obvious signals were identified with regard to medication use.

“Insulin is not suspected of having adverse effects closely related to COVID-19. RAAS blockers are not deleterious but indicative of hypertension, which is a comorbidity even in diabetes patients,” he said. (None of the patients studied were taking sodium-glucose cotransporter 2 inhibitors or glucagonlike peptide receptor agonists.)
 

_{Yet again, high BMI emerges as a major risk factor}

The study included 1,317 patients with diabetes and confirmed COVID-19 admitted to 53 French hospitals during March 10-31, 2020. Participants included 88.5% with type 2 diabetes, 3% with type 1 diabetes, and 3.1% newly diagnosed on admission. Mean age was 69.8 years.

Diabetes-related disorders on admission were reported in 11.1% of participants overall. These included 132 episodes of severe hyperglycemia, including 40 of ketosis, of which 19 were ketoacidosis, and 14 hypoglycemic events. Severe anorexia was reported in 6.3%.

The composite primary endpoint, tracheal intubation for mechanical ventilation and/or death within 7 days of admission, occurred in 29% of patients (n = 382).

Of the secondary outcomes, 31.1% (n = 410) were admitted to ICUs within 7 days of hospital admission, including 20.3% (n = 267) who required tracheal intubation for mechanical ventilation.

On day 7, 10.6% (n = 140) had died and 18.0% (n = 237) were discharged.

In the univariate analysis, the primary outcome was more frequent in men (69.1% vs. 63.2%; P = .0420) and those taking RAAS blockers (61.5% vs. 55.3%; P = .0386). Median BMI was significantly higher in those in whom the primary outcome occurred (29.1 vs 28.1 kg/m²; P = .0009),

Other characteristics prior to admission associated with risk of death on day 7 included age, hypertension, micro- and macrovascular diabetes-related complications, and comorbidities such as heart failure and treated obstructive sleep apnea.

Over 40% of those admitted had such complications. Of the patients analyzed, microvascular complications (eye, kidney, and neuropathy) were present in 47% and macrovascular complications (arteries of the heart, brain, and legs) were present in 41%.

Encouragingly, there were no deaths in patients aged under 65 years with type 1 diabetes, but only 39 participants had type 1 diabetes. Other work is ongoing to establish the effect of COVID-19 in this specific population, the researchers wrote.

Among prior medications, metformin use was lower in people who died, while insulin use, RAAS blockers, beta-blockers, loop diuretics, and mineralocorticoid-receptor antagonists were associated with death on day 7. The medication findings didn’t reach statistical significance, however.

When asked about the hint of a protective effect of metformin (odds ratio, 0.80; P = .4532), given that some experts have advised stopping it in the setting of COVID-19 because of the risk of lactic acidosis, Dr. Hadjadj said he wouldn’t necessarily stop it in all patients with COVID-19, but said, “let’s stop it in cases of severe condition.”
 

Analysis ongoing, ‘some new messages might pop up’

After adjustment for age and sex, BMI was significantly and positively associated with the primary outcome (P = .0001) but not with death on day 7 (P = .1488), and A_1c wasn’t associated with either outcome.

In a multivariable analysis that included characteristics prior to admission, BMI remained the only independent preadmission predictor associated with the primary outcome (adjusted odds ratio, 1.28), while factors independently associated with risk of death on day 7 included age, diabetes complication history, and treated obstructive sleep apnea.

And after adjustment for age and sex, admission plasma glucose level was significantly and positively associated with both the primary outcome (P = .0001) and death on day 7 (P = .0059).

In the multivariate analysis, admission characteristics that predicted the primary outcome were dyspnea, lymphopenia, increased AST, and increased C-reactive protein.

Dr. Hadjadj said his team is now “focusing on specific risk factors such as obesity, age, vascular complications, medications ... to perform some deeper analyses.”

“We look forward to analyzing the data on in-hospital stay up to day 28 after admission. Some new messages might well pop up,” he added.

But in the meantime, “Elderly populations with long-term diabetes with advanced diabetes-related complications and/or treated obstructive sleep apnea were particularly at risk of early death and might require specific management to avoid infection with the novel coronavirus,” the researchers stressed.

The study received funding from the Fondation Francophone de Recherche sur le Diabète and was supported by Novo Nordisk, MSD, Abbott, AstraZeneca, Lilly, and the Fédération Française des Diabétiques; Société Francophone du Diabète; and Air Liquide Healthcare International. Dr. Hadjadj reported receiving grants, personal fees, and/or nonfinancial support from AstraZeneca, Bayer, Boehringer Ingelheim, Dinno Santé, Eli Lilly, LVL, MSD, Novartis, Pierre Fabre Santé, Sanofi, Servier, and Valbiotis.

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

More than 1 in 10 people with diabetes hospitalized with COVID-19 die within a week, while nearly a third require mechanical ventilation, new research shows.

Data from the CORONADO (French Coronavirus SARS-CoV-2 and Diabetes Outcomes) study also revealed that body mass index (BMI) was independently associated with death or intubation at 7 days, while A_1c and use of renin-angiotensin-aldosterone system (RAAS) blockers and dipeptidyl peptidase–4 inhibitors were not.

The presence of diabetes-related complications and older age also increased the risk of death.

The findings were published online Diabetologia by Bertrand Cariou, MD, PhD, of the department of endocrinology at the Hôpital Guillaume et René Laennec in Nantes, France, and colleagues.
 

First study to examine specific characteristics at time of admission

Previous studies have linked diabetes to worse outcomes in COVID-19, but this is the first to examine specific characteristics before and at the time of hospital admission that predict worse outcomes among people with diabetes, study coauthor Samy Hadjadj, MD, PhD, said in an interview.

“Before the CORONADO study it was ‘all diabetes [patients] are the same.’ Now we can surely consider more precisely the risk, taking age, sex, BMI, complications, and [obstructive sleep apnea] as clear ‘very high-risk situations,’” said Dr. Hadjadj, of the same institution as Dr. Cariou.

Another clinical message, Dr. Hadjadj said, is that, “even in diabetes, each increase in BMI is associated with an increase in the risk of intubation and/or death in the 7 days following admission for COVID-19. So let’s target this population as a really important population to keep social distancing and stay alert on avoiding the virus.”

But he urged caution regarding the A_1c finding. “A_1c might be associated with admission to hospital but other factors far beyond A_1c drive the prognosis as soon as a patient is admitted. It’s surprising but reasonable speculation can explain this.”

And Dr. Hadjadj said that no obvious signals were identified with regard to medication use.

“Insulin is not suspected of having adverse effects closely related to COVID-19. RAAS blockers are not deleterious but indicative of hypertension, which is a comorbidity even in diabetes patients,” he said. (None of the patients studied were taking sodium-glucose cotransporter 2 inhibitors or glucagonlike peptide receptor agonists.)
 

_{Yet again, high BMI emerges as a major risk factor}

The study included 1,317 patients with diabetes and confirmed COVID-19 admitted to 53 French hospitals during March 10-31, 2020. Participants included 88.5% with type 2 diabetes, 3% with type 1 diabetes, and 3.1% newly diagnosed on admission. Mean age was 69.8 years.

Diabetes-related disorders on admission were reported in 11.1% of participants overall. These included 132 episodes of severe hyperglycemia, including 40 of ketosis, of which 19 were ketoacidosis, and 14 hypoglycemic events. Severe anorexia was reported in 6.3%.

The composite primary endpoint, tracheal intubation for mechanical ventilation and/or death within 7 days of admission, occurred in 29% of patients (n = 382).

Of the secondary outcomes, 31.1% (n = 410) were admitted to ICUs within 7 days of hospital admission, including 20.3% (n = 267) who required tracheal intubation for mechanical ventilation.

On day 7, 10.6% (n = 140) had died and 18.0% (n = 237) were discharged.

In the univariate analysis, the primary outcome was more frequent in men (69.1% vs. 63.2%; P = .0420) and those taking RAAS blockers (61.5% vs. 55.3%; P = .0386). Median BMI was significantly higher in those in whom the primary outcome occurred (29.1 vs 28.1 kg/m²; P = .0009),

Other characteristics prior to admission associated with risk of death on day 7 included age, hypertension, micro- and macrovascular diabetes-related complications, and comorbidities such as heart failure and treated obstructive sleep apnea.

Over 40% of those admitted had such complications. Of the patients analyzed, microvascular complications (eye, kidney, and neuropathy) were present in 47% and macrovascular complications (arteries of the heart, brain, and legs) were present in 41%.

Encouragingly, there were no deaths in patients aged under 65 years with type 1 diabetes, but only 39 participants had type 1 diabetes. Other work is ongoing to establish the effect of COVID-19 in this specific population, the researchers wrote.

Among prior medications, metformin use was lower in people who died, while insulin use, RAAS blockers, beta-blockers, loop diuretics, and mineralocorticoid-receptor antagonists were associated with death on day 7. The medication findings didn’t reach statistical significance, however.

When asked about the hint of a protective effect of metformin (odds ratio, 0.80; P = .4532), given that some experts have advised stopping it in the setting of COVID-19 because of the risk of lactic acidosis, Dr. Hadjadj said he wouldn’t necessarily stop it in all patients with COVID-19, but said, “let’s stop it in cases of severe condition.”
 

Analysis ongoing, ‘some new messages might pop up’

After adjustment for age and sex, BMI was significantly and positively associated with the primary outcome (P = .0001) but not with death on day 7 (P = .1488), and A_1c wasn’t associated with either outcome.

In a multivariable analysis that included characteristics prior to admission, BMI remained the only independent preadmission predictor associated with the primary outcome (adjusted odds ratio, 1.28), while factors independently associated with risk of death on day 7 included age, diabetes complication history, and treated obstructive sleep apnea.

And after adjustment for age and sex, admission plasma glucose level was significantly and positively associated with both the primary outcome (P = .0001) and death on day 7 (P = .0059).

In the multivariate analysis, admission characteristics that predicted the primary outcome were dyspnea, lymphopenia, increased AST, and increased C-reactive protein.

Dr. Hadjadj said his team is now “focusing on specific risk factors such as obesity, age, vascular complications, medications ... to perform some deeper analyses.”

“We look forward to analyzing the data on in-hospital stay up to day 28 after admission. Some new messages might well pop up,” he added.

But in the meantime, “Elderly populations with long-term diabetes with advanced diabetes-related complications and/or treated obstructive sleep apnea were particularly at risk of early death and might require specific management to avoid infection with the novel coronavirus,” the researchers stressed.

The study received funding from the Fondation Francophone de Recherche sur le Diabète and was supported by Novo Nordisk, MSD, Abbott, AstraZeneca, Lilly, and the Fédération Française des Diabétiques; Société Francophone du Diabète; and Air Liquide Healthcare International. Dr. Hadjadj reported receiving grants, personal fees, and/or nonfinancial support from AstraZeneca, Bayer, Boehringer Ingelheim, Dinno Santé, Eli Lilly, LVL, MSD, Novartis, Pierre Fabre Santé, Sanofi, Servier, and Valbiotis.

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

As mass protests continued in large and small cities across the country, officials expressed concerns on Sunday news shows about a potential spike in coronavirus cases in coming days.

“There’s going to be a lot of issues coming out of what’s happened in the last week, but one of them is going to be that chains of transmission will have become lit from these gatherings,” said Scott Gottlieb, former FDA commissioner, on the CBS News show “Face the Nation.”

In Minnesota, he noted, COVID-19 cases and hospitalizations increased in recent days – even before the protests started.

“We still have pockets of spread in communities that aren’t under good control,” he said.

The protests generally have started peacefully with some demonstrators following physical distancing rules. But they have evolved into sometimes violent gatherings of hundreds or thousands of people where standing 6 feet apart is impossible.

Chanting, singing, and shouting may spread the virus through respiratory droplets. In addition, people who have the virus but don’t show symptoms may infect others without knowing it.

“If you were out protesting last night, you probably need to go get a COVID test this week,” Atlanta Mayor Keisha Lance Bottoms said Saturday, according to the Associated Press.

Gottlieb and Bottoms also spoke Sunday about the disproportionate effect of the coronavirus on black and Hispanic people, who are contracting and dying from the virus at higher rates. Socioeconomic factors such as low incomes, limited health care access, underlying conditions and overcrowded housing play a role in the greater risk, Gottlieb said.

“It’s a symptom of broader racial inequities in our country that we need to work to resolve,” he said.

Protests against racial injustice, sparked by the death of George Floyd in Minneapolis last week, could harm those communities experiencing the most severe outcomes of the coronavirus, Bottoms added.

“We know what’s already happening in our community with this virus. We’re going to see the other side of this in a couple of weeks,” Bottoms said on CNN’s “State of the Union.”

The protests may affect the pandemic in other ways. Los Angeles Mayor Eric Garcetti said the city’s coronavirus testing centers were closed on Saturday because of “safety worries across the city,” according to KTLA.

“We need to make sure, especially in communities that have less power, that we are able to make sure people don’t disproportionately die because of the color of their skin,” he said. “We can’t do that when the city breaks down.”

This article first appeared on WebMD.com.

As mass protests continued in large and small cities across the country, officials expressed concerns on Sunday news shows about a potential spike in coronavirus cases in coming days.

“There’s going to be a lot of issues coming out of what’s happened in the last week, but one of them is going to be that chains of transmission will have become lit from these gatherings,” said Scott Gottlieb, former FDA commissioner, on the CBS News show “Face the Nation.”

In Minnesota, he noted, COVID-19 cases and hospitalizations increased in recent days – even before the protests started.

“We still have pockets of spread in communities that aren’t under good control,” he said.

The protests generally have started peacefully with some demonstrators following physical distancing rules. But they have evolved into sometimes violent gatherings of hundreds or thousands of people where standing 6 feet apart is impossible.

Chanting, singing, and shouting may spread the virus through respiratory droplets. In addition, people who have the virus but don’t show symptoms may infect others without knowing it.

“If you were out protesting last night, you probably need to go get a COVID test this week,” Atlanta Mayor Keisha Lance Bottoms said Saturday, according to the Associated Press.

Gottlieb and Bottoms also spoke Sunday about the disproportionate effect of the coronavirus on black and Hispanic people, who are contracting and dying from the virus at higher rates. Socioeconomic factors such as low incomes, limited health care access, underlying conditions and overcrowded housing play a role in the greater risk, Gottlieb said.

“It’s a symptom of broader racial inequities in our country that we need to work to resolve,” he said.

Protests against racial injustice, sparked by the death of George Floyd in Minneapolis last week, could harm those communities experiencing the most severe outcomes of the coronavirus, Bottoms added.

“We know what’s already happening in our community with this virus. We’re going to see the other side of this in a couple of weeks,” Bottoms said on CNN’s “State of the Union.”

The protests may affect the pandemic in other ways. Los Angeles Mayor Eric Garcetti said the city’s coronavirus testing centers were closed on Saturday because of “safety worries across the city,” according to KTLA.

“We need to make sure, especially in communities that have less power, that we are able to make sure people don’t disproportionately die because of the color of their skin,” he said. “We can’t do that when the city breaks down.”

This article first appeared on WebMD.com.

As mass protests continued in large and small cities across the country, officials expressed concerns on Sunday news shows about a potential spike in coronavirus cases in coming days.

“There’s going to be a lot of issues coming out of what’s happened in the last week, but one of them is going to be that chains of transmission will have become lit from these gatherings,” said Scott Gottlieb, former FDA commissioner, on the CBS News show “Face the Nation.”

In Minnesota, he noted, COVID-19 cases and hospitalizations increased in recent days – even before the protests started.

“We still have pockets of spread in communities that aren’t under good control,” he said.

The protests generally have started peacefully with some demonstrators following physical distancing rules. But they have evolved into sometimes violent gatherings of hundreds or thousands of people where standing 6 feet apart is impossible.

Chanting, singing, and shouting may spread the virus through respiratory droplets. In addition, people who have the virus but don’t show symptoms may infect others without knowing it.

“If you were out protesting last night, you probably need to go get a COVID test this week,” Atlanta Mayor Keisha Lance Bottoms said Saturday, according to the Associated Press.

Gottlieb and Bottoms also spoke Sunday about the disproportionate effect of the coronavirus on black and Hispanic people, who are contracting and dying from the virus at higher rates. Socioeconomic factors such as low incomes, limited health care access, underlying conditions and overcrowded housing play a role in the greater risk, Gottlieb said.

“It’s a symptom of broader racial inequities in our country that we need to work to resolve,” he said.

Protests against racial injustice, sparked by the death of George Floyd in Minneapolis last week, could harm those communities experiencing the most severe outcomes of the coronavirus, Bottoms added.

“We know what’s already happening in our community with this virus. We’re going to see the other side of this in a couple of weeks,” Bottoms said on CNN’s “State of the Union.”

The protests may affect the pandemic in other ways. Los Angeles Mayor Eric Garcetti said the city’s coronavirus testing centers were closed on Saturday because of “safety worries across the city,” according to KTLA.

“We need to make sure, especially in communities that have less power, that we are able to make sure people don’t disproportionately die because of the color of their skin,” he said. “We can’t do that when the city breaks down.”

This article first appeared on WebMD.com.

Prior to the current crisis of COVID-19, I had a critical view of the direction of our psychiatric field. We have given up on complicated psychotherapies in favor of dispensing medications. We have given up on complicated diagnostic assessments in favor of simple self-rated symptoms questionnaires. Many of us even chose to give up on seeing patients face to face in favor of practicing telepsychiatry in the comfort of our homes. Some even promoted a future of psychiatry in which psychiatrists treated patients through large spreadsheets of evidence-based rating tools following evidence-based algorithms without even ever meeting the patients.

I do not view this problem as unique to psychiatry but rather as part of a larger trend in society. For the past couple of years, Vivek Murthy, MD, the former U.S. surgeon general, has popularized the idea that we are in a loneliness epidemic, saying, “We live in the most technologically connected age in the history of civilization, yet rates of loneliness have doubled since the 1980s.” Despite having enumerable means to reach other human beings, so many of us feel distant and out of touch with others. This loneliness has a measurable impact on our well-being with one study that states, “Actual and perceived social isolation are both associated with increased risk for early mortality.”

Then, seemingly out of nowhere, we were confronted with the largest challenge to our sense of connectedness in my lifetime. Throughout the past months, we have been asked to meet each other less frequently, do so through sterile means, and certainly not shake hands, hug, or embrace. The COVID-19 crisis has quickly made us all experts in telepsychiatry, remote work, and doing more with less. The COVID-19 crisis has asked many of us to put aside some of our human rituals like eating together, enjoying artistic experiences as a group, and touching, for the sake of saving lives.

For many, socially distancing has been a considerable added stressor – a stressor that continues to test humanity’s ability to be resilient. I am saddened by prior patients reaching out to seek comfort in these difficult times. I am touched by their desire to reconnect with someone they know, someone who feels familiar. I am surprised by the power of connection through phone and video calls. For some patients, despite the added burden, the current crisis has been an opportunity for their mental health and a reminder of the things that are important, including calling old friends and staying in touch with those who matter the most.

Yet, as the social restrictions continue, the stressors mount and the resilience becomes harder to find. Checking in on others can become a chore. The social norm to partake in fashion, and self-care, become harder to find. In some cases, even hygiene and our health take a side role. The weekly phone visits with a therapist can feel just as mundane and repetitive as life. Sleep becomes harder to find, and food loses its taste. At this point, we realize the humanity that we lost in all this.

In the past couple of months, we have all become much more aware of the fragility of connectedness. However, we should recognize that the impact was well on its way before the COVID-19 crisis. It is my opinion that psychiatry should champion the issue of human relations. I do not think that we need to wait for a new DSM diagnosis, an evidence-based paradigm, or a Food and Drug Administration–approved medication to do so. The COVID-19 crisis has rendered us all cognizant of the importance of relationships.

While it may be that psychiatry continues to foray in electronic means of communication, use of impersonal scales and diagnosis, as well as anonymized algorithmic treatment plans, we should also promote as much humanity as society and public health safety will permit. Getting dressed to see your psychiatrist, face to face, to have an open-ended conversation about the nature of one’s life has clearly become something precious and powerful that should be cherished and protected. My hope is the rules and mandates we are required to use during the pandemic today do not become a continued habit that result in further loneliness and disconnect. If we chose to, the lessons we learn today can, in fact, strengthen our appreciation and pursuit of human connection.
 

Dr. Badre is a forensic psychiatrist in San Diego and an expert in correctional mental health. He holds teaching positions at the University of California, San Diego, and the University of San Diego. He teaches medical education, psychopharmacology, ethics in psychiatry, and correctional care. Among his writings is chapter 7 in the book “Critical Psychiatry: Controversies and Clinical Implications” (Springer, 2019). He has no disclosures.

Prior to the current crisis of COVID-19, I had a critical view of the direction of our psychiatric field. We have given up on complicated psychotherapies in favor of dispensing medications. We have given up on complicated diagnostic assessments in favor of simple self-rated symptoms questionnaires. Many of us even chose to give up on seeing patients face to face in favor of practicing telepsychiatry in the comfort of our homes. Some even promoted a future of psychiatry in which psychiatrists treated patients through large spreadsheets of evidence-based rating tools following evidence-based algorithms without even ever meeting the patients.

I do not view this problem as unique to psychiatry but rather as part of a larger trend in society. For the past couple of years, Vivek Murthy, MD, the former U.S. surgeon general, has popularized the idea that we are in a loneliness epidemic, saying, “We live in the most technologically connected age in the history of civilization, yet rates of loneliness have doubled since the 1980s.” Despite having enumerable means to reach other human beings, so many of us feel distant and out of touch with others. This loneliness has a measurable impact on our well-being with one study that states, “Actual and perceived social isolation are both associated with increased risk for early mortality.”

Then, seemingly out of nowhere, we were confronted with the largest challenge to our sense of connectedness in my lifetime. Throughout the past months, we have been asked to meet each other less frequently, do so through sterile means, and certainly not shake hands, hug, or embrace. The COVID-19 crisis has quickly made us all experts in telepsychiatry, remote work, and doing more with less. The COVID-19 crisis has asked many of us to put aside some of our human rituals like eating together, enjoying artistic experiences as a group, and touching, for the sake of saving lives.

For many, socially distancing has been a considerable added stressor – a stressor that continues to test humanity’s ability to be resilient. I am saddened by prior patients reaching out to seek comfort in these difficult times. I am touched by their desire to reconnect with someone they know, someone who feels familiar. I am surprised by the power of connection through phone and video calls. For some patients, despite the added burden, the current crisis has been an opportunity for their mental health and a reminder of the things that are important, including calling old friends and staying in touch with those who matter the most.

Yet, as the social restrictions continue, the stressors mount and the resilience becomes harder to find. Checking in on others can become a chore. The social norm to partake in fashion, and self-care, become harder to find. In some cases, even hygiene and our health take a side role. The weekly phone visits with a therapist can feel just as mundane and repetitive as life. Sleep becomes harder to find, and food loses its taste. At this point, we realize the humanity that we lost in all this.

In the past couple of months, we have all become much more aware of the fragility of connectedness. However, we should recognize that the impact was well on its way before the COVID-19 crisis. It is my opinion that psychiatry should champion the issue of human relations. I do not think that we need to wait for a new DSM diagnosis, an evidence-based paradigm, or a Food and Drug Administration–approved medication to do so. The COVID-19 crisis has rendered us all cognizant of the importance of relationships.

While it may be that psychiatry continues to foray in electronic means of communication, use of impersonal scales and diagnosis, as well as anonymized algorithmic treatment plans, we should also promote as much humanity as society and public health safety will permit. Getting dressed to see your psychiatrist, face to face, to have an open-ended conversation about the nature of one’s life has clearly become something precious and powerful that should be cherished and protected. My hope is the rules and mandates we are required to use during the pandemic today do not become a continued habit that result in further loneliness and disconnect. If we chose to, the lessons we learn today can, in fact, strengthen our appreciation and pursuit of human connection.
 

Dr. Badre is a forensic psychiatrist in San Diego and an expert in correctional mental health. He holds teaching positions at the University of California, San Diego, and the University of San Diego. He teaches medical education, psychopharmacology, ethics in psychiatry, and correctional care. Among his writings is chapter 7 in the book “Critical Psychiatry: Controversies and Clinical Implications” (Springer, 2019). He has no disclosures.

Prior to the current crisis of COVID-19, I had a critical view of the direction of our psychiatric field. We have given up on complicated psychotherapies in favor of dispensing medications. We have given up on complicated diagnostic assessments in favor of simple self-rated symptoms questionnaires. Many of us even chose to give up on seeing patients face to face in favor of practicing telepsychiatry in the comfort of our homes. Some even promoted a future of psychiatry in which psychiatrists treated patients through large spreadsheets of evidence-based rating tools following evidence-based algorithms without even ever meeting the patients.

I do not view this problem as unique to psychiatry but rather as part of a larger trend in society. For the past couple of years, Vivek Murthy, MD, the former U.S. surgeon general, has popularized the idea that we are in a loneliness epidemic, saying, “We live in the most technologically connected age in the history of civilization, yet rates of loneliness have doubled since the 1980s.” Despite having enumerable means to reach other human beings, so many of us feel distant and out of touch with others. This loneliness has a measurable impact on our well-being with one study that states, “Actual and perceived social isolation are both associated with increased risk for early mortality.”

Then, seemingly out of nowhere, we were confronted with the largest challenge to our sense of connectedness in my lifetime. Throughout the past months, we have been asked to meet each other less frequently, do so through sterile means, and certainly not shake hands, hug, or embrace. The COVID-19 crisis has quickly made us all experts in telepsychiatry, remote work, and doing more with less. The COVID-19 crisis has asked many of us to put aside some of our human rituals like eating together, enjoying artistic experiences as a group, and touching, for the sake of saving lives.

For many, socially distancing has been a considerable added stressor – a stressor that continues to test humanity’s ability to be resilient. I am saddened by prior patients reaching out to seek comfort in these difficult times. I am touched by their desire to reconnect with someone they know, someone who feels familiar. I am surprised by the power of connection through phone and video calls. For some patients, despite the added burden, the current crisis has been an opportunity for their mental health and a reminder of the things that are important, including calling old friends and staying in touch with those who matter the most.

Yet, as the social restrictions continue, the stressors mount and the resilience becomes harder to find. Checking in on others can become a chore. The social norm to partake in fashion, and self-care, become harder to find. In some cases, even hygiene and our health take a side role. The weekly phone visits with a therapist can feel just as mundane and repetitive as life. Sleep becomes harder to find, and food loses its taste. At this point, we realize the humanity that we lost in all this.

In the past couple of months, we have all become much more aware of the fragility of connectedness. However, we should recognize that the impact was well on its way before the COVID-19 crisis. It is my opinion that psychiatry should champion the issue of human relations. I do not think that we need to wait for a new DSM diagnosis, an evidence-based paradigm, or a Food and Drug Administration–approved medication to do so. The COVID-19 crisis has rendered us all cognizant of the importance of relationships.

While it may be that psychiatry continues to foray in electronic means of communication, use of impersonal scales and diagnosis, as well as anonymized algorithmic treatment plans, we should also promote as much humanity as society and public health safety will permit. Getting dressed to see your psychiatrist, face to face, to have an open-ended conversation about the nature of one’s life has clearly become something precious and powerful that should be cherished and protected. My hope is the rules and mandates we are required to use during the pandemic today do not become a continued habit that result in further loneliness and disconnect. If we chose to, the lessons we learn today can, in fact, strengthen our appreciation and pursuit of human connection.
 

Dr. Badre is a forensic psychiatrist in San Diego and an expert in correctional mental health. He holds teaching positions at the University of California, San Diego, and the University of San Diego. He teaches medical education, psychopharmacology, ethics in psychiatry, and correctional care. Among his writings is chapter 7 in the book “Critical Psychiatry: Controversies and Clinical Implications” (Springer, 2019). He has no disclosures.

Pembrolizumab treatment significantly improved progression-free survival versus brentuximab vedotin in a randomized, phase 3 trial including patients with relapsed or refractory classical Hodgkin lymphoma, an investigator has reported.

Median progression-free survival (PFS) was 13.2 versus 8.3 months in favor of pembrolizumab, according to the report on the KEYNOTE-204 trial, which included patients with classical Hodgkin lymphoma who either had relapsed after autologous stem cell transplant (SCT) or were ineligible for autologous SCT.

The PFS improvement was “statistically significant and clinically meaningful,” said investigator John Kuruvilla, MD, of Princess Margaret Cancer Centre in Toronto.

“This PFS benefit extended to key subgroups, including those ineligible for autologous transplant, patients with primary refractory disease, and patients who were brentuximab-vedotin naive,” Dr. Kuruvilla added in his presentation, which was part of the American Society of Clinical Oncology virtual scientific program.

Pneumonitis was more frequent in the pembrolizumab arm, but “appeared in general to be quite well managed” among patients who experienced this adverse event, according to Dr. Kuruvilla, who said that treatment with the programmed death–1 inhibitor should be considered “the preferred treatment option and the new standard of care” for patients with relapsed/refractory classic Hodgkin lymphoma who have relapsed after autologous SCT or are ineligible for it.

Although the pneumonitis findings are important to keep in mind, results of KEYNOTE-204 are indeed “practice defining” and immediately impactful, said Mark J. Roschewski, MD, clinical investigator in the lymphoid malignancies branch at the Center for Cancer Research, part of the National Cancer Institute, Bethesda, Md.

“I would select pembrolizumab over brentuximab for this patient population, particularly those that are refractory to chemotherapy,” he said in a commentary on the study also included in the virtual ASCO proceedings.

“There may be specific patient populations that I’d reconsider, such as those that might be at high risk for lung toxicity,” he added. “They may not be suitable for this, but it’s something to at least to be aware of.”

Although the antibody-drug conjugate brentuximab vedotin has been considered the standard of care for patients with relapse after autologous SCT, there has historically been no standard of care for patients who are ineligible for transplant because of chemorefractory disease, advanced age, or comorbidities, Dr. Kuruvilla said in his presentation.

In the KEYNOTE-204 study, 304 patients with relapsed/refractory classic Hodgkin lymphoma were randomized to receive either pembrolizumab 200 mg or brentuximab at 1.8 mg/kg intravenously every 3 weeks for up to 35 cycles.

The median age of patients was 36 years in the pembrolizumab arm and 35 years in the brentuximab vedotin arm, according to the report. Approximately 37% of the patients had previously undergone autologous SCT. About 40% had been refractory to frontline therapy, while 28% relapsed within 12 months of therapy and 32% relapsed later than 12 months.

Median PFS by blinded independent central review was 13.2 versus 8.3 months in the pembrolizumab and brentuximab arms, respectively (hazard ratio, 0.65; 95% confidence interval, 0.48-0.88; P = .00271), Dr. Kuruvilla reported.

The benefit extended to “key subgroups” in the trial, he added, including those who were ineligible for autologous SCT, those with primary refractory disease, and those who were naive to brentuximab vedotin, with HRs of 0.61, 0.52, and 0.67, respectively.

Pembrolizumab was also associated with more durable responses versus brentuximab vedotin, according to the investigator.

The overall response rate was 65.6% and 54.2%, respectively, for pembrolizumab and brentuximab, although this difference of approximately 11 percentage points did not meet criteria for statistical significance, he said. Duration of response was 20.7 months or pembrolizumab and 13.8 months for brentuximab.

The rate of serious treatment-related adverse events was similar between groups, according to Dr. Kuruvilla, who reported grade 3-5 events occurring in 19.6% and 25.0% of the pembrolizumab and brentuximab arms. Serious treatment-related adverse events were numerically more frequent in the pembrolizumab arm (16.2% vs. 10.5%) and there was one treatment-related death caused by pneumonia, seen in the pembrolizumab arm.

Pneumonitis occurred in 2.6% of the brentuximab-treated patients and in 10.8% of pembrolizumab-treated patients, of which half of cases were grade 3-4, according to the report.

In the pembrolizumab arm, pneumonitis was felt to be drug-related in 15 of 16 cases, according to Dr. Kuruvilla, who added that 15 of 16 patients required corticosteroid therapy. “This has led to the resolution of the pneumonitis in 12 of 16 patients, with ongoing resolution in one further patient.”

Research funding for KEYNOTE-204 came from Merck Sharp & Dohme. Dr. Kuruvilla provided disclosures related to Merck and a variety of other pharmaceutical companies. Dr. Roschewski said he had no relationships to disclose.

SOURCE: Kuruvilla J et al. ASCO 2020, Abstract 8005.

Pembrolizumab treatment significantly improved progression-free survival versus brentuximab vedotin in a randomized, phase 3 trial including patients with relapsed or refractory classical Hodgkin lymphoma, an investigator has reported.

Median progression-free survival (PFS) was 13.2 versus 8.3 months in favor of pembrolizumab, according to the report on the KEYNOTE-204 trial, which included patients with classical Hodgkin lymphoma who either had relapsed after autologous stem cell transplant (SCT) or were ineligible for autologous SCT.

The PFS improvement was “statistically significant and clinically meaningful,” said investigator John Kuruvilla, MD, of Princess Margaret Cancer Centre in Toronto.

“This PFS benefit extended to key subgroups, including those ineligible for autologous transplant, patients with primary refractory disease, and patients who were brentuximab-vedotin naive,” Dr. Kuruvilla added in his presentation, which was part of the American Society of Clinical Oncology virtual scientific program.

Pneumonitis was more frequent in the pembrolizumab arm, but “appeared in general to be quite well managed” among patients who experienced this adverse event, according to Dr. Kuruvilla, who said that treatment with the programmed death–1 inhibitor should be considered “the preferred treatment option and the new standard of care” for patients with relapsed/refractory classic Hodgkin lymphoma who have relapsed after autologous SCT or are ineligible for it.

Although the pneumonitis findings are important to keep in mind, results of KEYNOTE-204 are indeed “practice defining” and immediately impactful, said Mark J. Roschewski, MD, clinical investigator in the lymphoid malignancies branch at the Center for Cancer Research, part of the National Cancer Institute, Bethesda, Md.

“I would select pembrolizumab over brentuximab for this patient population, particularly those that are refractory to chemotherapy,” he said in a commentary on the study also included in the virtual ASCO proceedings.

“There may be specific patient populations that I’d reconsider, such as those that might be at high risk for lung toxicity,” he added. “They may not be suitable for this, but it’s something to at least to be aware of.”

Although the antibody-drug conjugate brentuximab vedotin has been considered the standard of care for patients with relapse after autologous SCT, there has historically been no standard of care for patients who are ineligible for transplant because of chemorefractory disease, advanced age, or comorbidities, Dr. Kuruvilla said in his presentation.

In the KEYNOTE-204 study, 304 patients with relapsed/refractory classic Hodgkin lymphoma were randomized to receive either pembrolizumab 200 mg or brentuximab at 1.8 mg/kg intravenously every 3 weeks for up to 35 cycles.

The median age of patients was 36 years in the pembrolizumab arm and 35 years in the brentuximab vedotin arm, according to the report. Approximately 37% of the patients had previously undergone autologous SCT. About 40% had been refractory to frontline therapy, while 28% relapsed within 12 months of therapy and 32% relapsed later than 12 months.

Median PFS by blinded independent central review was 13.2 versus 8.3 months in the pembrolizumab and brentuximab arms, respectively (hazard ratio, 0.65; 95% confidence interval, 0.48-0.88; P = .00271), Dr. Kuruvilla reported.

The benefit extended to “key subgroups” in the trial, he added, including those who were ineligible for autologous SCT, those with primary refractory disease, and those who were naive to brentuximab vedotin, with HRs of 0.61, 0.52, and 0.67, respectively.

Pembrolizumab was also associated with more durable responses versus brentuximab vedotin, according to the investigator.

The overall response rate was 65.6% and 54.2%, respectively, for pembrolizumab and brentuximab, although this difference of approximately 11 percentage points did not meet criteria for statistical significance, he said. Duration of response was 20.7 months or pembrolizumab and 13.8 months for brentuximab.

The rate of serious treatment-related adverse events was similar between groups, according to Dr. Kuruvilla, who reported grade 3-5 events occurring in 19.6% and 25.0% of the pembrolizumab and brentuximab arms. Serious treatment-related adverse events were numerically more frequent in the pembrolizumab arm (16.2% vs. 10.5%) and there was one treatment-related death caused by pneumonia, seen in the pembrolizumab arm.

Pneumonitis occurred in 2.6% of the brentuximab-treated patients and in 10.8% of pembrolizumab-treated patients, of which half of cases were grade 3-4, according to the report.

In the pembrolizumab arm, pneumonitis was felt to be drug-related in 15 of 16 cases, according to Dr. Kuruvilla, who added that 15 of 16 patients required corticosteroid therapy. “This has led to the resolution of the pneumonitis in 12 of 16 patients, with ongoing resolution in one further patient.”

Research funding for KEYNOTE-204 came from Merck Sharp & Dohme. Dr. Kuruvilla provided disclosures related to Merck and a variety of other pharmaceutical companies. Dr. Roschewski said he had no relationships to disclose.

SOURCE: Kuruvilla J et al. ASCO 2020, Abstract 8005.

Pembrolizumab treatment significantly improved progression-free survival versus brentuximab vedotin in a randomized, phase 3 trial including patients with relapsed or refractory classical Hodgkin lymphoma, an investigator has reported.

Median progression-free survival (PFS) was 13.2 versus 8.3 months in favor of pembrolizumab, according to the report on the KEYNOTE-204 trial, which included patients with classical Hodgkin lymphoma who either had relapsed after autologous stem cell transplant (SCT) or were ineligible for autologous SCT.

The PFS improvement was “statistically significant and clinically meaningful,” said investigator John Kuruvilla, MD, of Princess Margaret Cancer Centre in Toronto.

“This PFS benefit extended to key subgroups, including those ineligible for autologous transplant, patients with primary refractory disease, and patients who were brentuximab-vedotin naive,” Dr. Kuruvilla added in his presentation, which was part of the American Society of Clinical Oncology virtual scientific program.

Pneumonitis was more frequent in the pembrolizumab arm, but “appeared in general to be quite well managed” among patients who experienced this adverse event, according to Dr. Kuruvilla, who said that treatment with the programmed death–1 inhibitor should be considered “the preferred treatment option and the new standard of care” for patients with relapsed/refractory classic Hodgkin lymphoma who have relapsed after autologous SCT or are ineligible for it.

Although the pneumonitis findings are important to keep in mind, results of KEYNOTE-204 are indeed “practice defining” and immediately impactful, said Mark J. Roschewski, MD, clinical investigator in the lymphoid malignancies branch at the Center for Cancer Research, part of the National Cancer Institute, Bethesda, Md.

“I would select pembrolizumab over brentuximab for this patient population, particularly those that are refractory to chemotherapy,” he said in a commentary on the study also included in the virtual ASCO proceedings.

“There may be specific patient populations that I’d reconsider, such as those that might be at high risk for lung toxicity,” he added. “They may not be suitable for this, but it’s something to at least to be aware of.”

Although the antibody-drug conjugate brentuximab vedotin has been considered the standard of care for patients with relapse after autologous SCT, there has historically been no standard of care for patients who are ineligible for transplant because of chemorefractory disease, advanced age, or comorbidities, Dr. Kuruvilla said in his presentation.

In the KEYNOTE-204 study, 304 patients with relapsed/refractory classic Hodgkin lymphoma were randomized to receive either pembrolizumab 200 mg or brentuximab at 1.8 mg/kg intravenously every 3 weeks for up to 35 cycles.

The median age of patients was 36 years in the pembrolizumab arm and 35 years in the brentuximab vedotin arm, according to the report. Approximately 37% of the patients had previously undergone autologous SCT. About 40% had been refractory to frontline therapy, while 28% relapsed within 12 months of therapy and 32% relapsed later than 12 months.

Median PFS by blinded independent central review was 13.2 versus 8.3 months in the pembrolizumab and brentuximab arms, respectively (hazard ratio, 0.65; 95% confidence interval, 0.48-0.88; P = .00271), Dr. Kuruvilla reported.

The benefit extended to “key subgroups” in the trial, he added, including those who were ineligible for autologous SCT, those with primary refractory disease, and those who were naive to brentuximab vedotin, with HRs of 0.61, 0.52, and 0.67, respectively.

Pembrolizumab was also associated with more durable responses versus brentuximab vedotin, according to the investigator.

The overall response rate was 65.6% and 54.2%, respectively, for pembrolizumab and brentuximab, although this difference of approximately 11 percentage points did not meet criteria for statistical significance, he said. Duration of response was 20.7 months or pembrolizumab and 13.8 months for brentuximab.

The rate of serious treatment-related adverse events was similar between groups, according to Dr. Kuruvilla, who reported grade 3-5 events occurring in 19.6% and 25.0% of the pembrolizumab and brentuximab arms. Serious treatment-related adverse events were numerically more frequent in the pembrolizumab arm (16.2% vs. 10.5%) and there was one treatment-related death caused by pneumonia, seen in the pembrolizumab arm.

Pneumonitis occurred in 2.6% of the brentuximab-treated patients and in 10.8% of pembrolizumab-treated patients, of which half of cases were grade 3-4, according to the report.

In the pembrolizumab arm, pneumonitis was felt to be drug-related in 15 of 16 cases, according to Dr. Kuruvilla, who added that 15 of 16 patients required corticosteroid therapy. “This has led to the resolution of the pneumonitis in 12 of 16 patients, with ongoing resolution in one further patient.”

Research funding for KEYNOTE-204 came from Merck Sharp & Dohme. Dr. Kuruvilla provided disclosures related to Merck and a variety of other pharmaceutical companies. Dr. Roschewski said he had no relationships to disclose.

SOURCE: Kuruvilla J et al. ASCO 2020, Abstract 8005.

Three main reasons have been put forth for using corticosteroids in critically ill patients with COVID-19, but only one – the hope of preventing lung fibrosis in patients with unresolved acute respiratory distress syndrome – is reasonable to employ now outside of formal randomized trials, Peter Pickkers, MD, PhD, asserted at a webinar on COVID-19 sponsored by the European Society of Intensive Care Medicine.

The most commonly invoked rationale for giving steroids in patients with severe COVID-19 is to modulate the destructive inflammatory immune response that occurs with advancing disease. Another justification cited for giving steroids is to treat suspected adrenal insufficiency in those with refractory shock. Of note, both practices are endorsed in the recent Surviving Sepsis Campaign guidelines on management of critically ill patients with COVID-19 (Intensive Care Med. 2020 May;46[5]:854-87).

But those recommendations – numbers 22 and 42 out of a total of 50 recommendations included in the guidelines – should never have been made, according to Dr. Pickkers, professor of experimental intensive care medicine at Radboud University Medical Center in Nijmegen, the Netherlands.
 

Dueling guidelines

The Surviving Sepsis Campaign guidelines, which were developed by a panel comprising 36 experts in 12 countries, are quite frank in conceding that the guidance in favor of corticosteroids are weak recommendations based on low-quality evidence.

The guidelines recommend against using corticosteroids to try to modulate the immune system in mechanically ventilated COVID-19 patients without acute respiratory distress syndrome (ARDS), but do recommend steroids in those with COVID-19 and ARDS. However, the guidelines also note that, because of the very low quality of the evidence, some experts on the panel preferred not to issue a pro-steroids recommendation at all until higher-quality evidence becomes available. Dr. Pickkers said he believes that the minority view should have prevailed. Moreover, current COVID-19 guidance from the World Health Organization is at odds with the Surviving Sepsis Campaign recommendations; the WHO advises against corticosteroids unless the treatment is indicated for a reason other than immunomodulation, he noted.

The evidence in favor of steroids in an effort to blunt the immune response in COVID patients with ARDS is based largely upon a single small, retrospective, non–peer-reviewed report that 5-7 days of treatment with 1-2 mg/kg per day of methylprednisolone was associated with shortened fever duration and need for supplemental oxygen.

The evidence against steroids for immunomodulation comes mainly from earlier studies of the SARS and MERS novel coronaviruses. For example, in a multicenter study of 309 patients with the MERS (Middle East respiratory syndrome) virus, those who received corticosteroids received no benefit and experienced delayed viral clearance (Am J Respir Crit Care Med. 2018 Mar 15;197[6]:757-67).

“The thing is, virtually all COVID-19 patients in the ICU fulfill the criteria for ARDS, so following the Surviving Sepsis Campaign guidelines would have far-reaching consequences,” Dr. Pickkers said.

Those consequences include a theoretic potential for serious harm arising from dampening the immune response at a point in the course of COVID-19 when the virus is still present, which could result in slowed viral clearance and prolonged viral shedding. Moreover so far no one has been able to identify a sweet spot in the disease course where the viral load has waned and the immune response is sufficiently early that intervention with corticosteroids might have an optimal benefit/risk ratio, he continued.

“My opinion is that at this moment there is no benefit at all for corticosteroids for immunomodulation in patients with COVID-19,” Dr. Pickkers said. “My personal recommendation, in contrast to the Surviving Sepsis Campaign recommendation, is not to use this therapy outside of a study.”

He added that randomized, controlled trials of corticosteroid therapy in critically ill patients with COVID-19 are ongoing in Europe and the United States, including the large RECOVERY study of dexamethasone in the United Kingdom.

As for the Surviving Sepsis Campaign recommendation to use corticosteroids to treat refractory shock in COVID-19, Dr. Pickkers dismissed this guidance as largely irrelevant. That’s because few patients with COVID-19 who need mechanical ventilation have refractory shock as evidenced by the need for a high infusion rate of norepinephrine. Anyway, he noted, that Surviving Sepsis recommendation is based upon extrapolation from evidence of benefit in bacterial septic shock patients, which he deemed to be of questionable relevance to the COVID-19 pandemic.
 

Attacking the fibroproliferative phase of ARDS

First off, Dr. Pickkers conceded, there is no evidence that treatment with corticosteroids to prevent lung fibrosis in COVID-19 patients with nonresolving ARDS is an effective strategy; the pandemic is simply too new at this point for the appropriate studies to have been done. But this much is known: Postmortem pathologic studies show fibroplastic proliferation is present in the lungs of COVID-19 patients, as in those who die of ARDS of other causes. Also, COVID-19 patients typically aren’t admitted to the ICU until day 11 or 12 after developing their first symptoms, so by the time they display indications that their ARDS is not resolving, the virus has typically left the scene; thus, there is little risk at that point that corticosteroids will promote viral proliferation. Additionally, studies in critically ill patients with nonresolving ARDS of other causes show clinically meaningful benefits for corticosteroid therapy.

Dr. Pickkers cited as “must reading” an analysis of five randomized trials of corticosteroid therapy in a total of 518 patients with acute lung injury ARDS of non–COVID-19 origin. The analysis by investigators at the University of Tennessee, Memphis, concluded that treatment resulted in clinically meaningful reductions in duration of mechanical ventilation and ICU length of stay. Moreover, in the 400 patients whose steroid therapy commenced before day 14 of ARDS, there was a statistically significant 22% reduction in risk of death, compared with patients in whom corticosteroids were started later (Intensive Care Med. 2008 Jan;34[1]:61-9).

Session cochair Jan De Waele, MD, PhD, struck a cautious note, remarking, “It’s my perception that we’re using the evidence that we’ve gathered in other conditions and are now trying to apply it in COVID-19. But quality data on patients with COVID-19 itself is pretty scare, and it’s really hard to say whether this disease behaves similarly to bacterial septic shock or to other viral infections.”

“We need more information about the use of corticosteroids in COVID-19, although I think a lot of people are using it at this moment,” added Dr. De Waele, a surgical intensivist at Ghent (Belgium) University.

That being said, he asked Dr. Pickkers when he considers using corticosteroids to prevent pulmonary fibrosis.

Dr. Pickkers said that when he notices that a COVID-19 patient’s lung compliance is worsening, that stiff lung is a clue that fibrosis is occurring and is having clinical consequences. “We also measure blood procollagen, a not very sensitive but moderately specific marker of fibroproliferation. If we see an increase in this biomarker and the lung mechanics are changing, then we do treat these patients with corticosteroids,” Dr. Pickkers replied.

He and his colleagues try to start steroids before day 14 of ARDS, and they continue treatment for longer than 7 days in order to prevent a rebound inflammatory response upon treatment discontinuation. They also avoid using neuromuscular agents and engage in meticulous infection surveillance in order to minimize potential complications of corticosteroid therapy in the ICU.

Dr. Pickkers reported having no financial conflicts regarding his presentation.

[email protected]

Three main reasons have been put forth for using corticosteroids in critically ill patients with COVID-19, but only one – the hope of preventing lung fibrosis in patients with unresolved acute respiratory distress syndrome – is reasonable to employ now outside of formal randomized trials, Peter Pickkers, MD, PhD, asserted at a webinar on COVID-19 sponsored by the European Society of Intensive Care Medicine.

The most commonly invoked rationale for giving steroids in patients with severe COVID-19 is to modulate the destructive inflammatory immune response that occurs with advancing disease. Another justification cited for giving steroids is to treat suspected adrenal insufficiency in those with refractory shock. Of note, both practices are endorsed in the recent Surviving Sepsis Campaign guidelines on management of critically ill patients with COVID-19 (Intensive Care Med. 2020 May;46[5]:854-87).

But those recommendations – numbers 22 and 42 out of a total of 50 recommendations included in the guidelines – should never have been made, according to Dr. Pickkers, professor of experimental intensive care medicine at Radboud University Medical Center in Nijmegen, the Netherlands.
 

Dueling guidelines

The Surviving Sepsis Campaign guidelines, which were developed by a panel comprising 36 experts in 12 countries, are quite frank in conceding that the guidance in favor of corticosteroids are weak recommendations based on low-quality evidence.

The guidelines recommend against using corticosteroids to try to modulate the immune system in mechanically ventilated COVID-19 patients without acute respiratory distress syndrome (ARDS), but do recommend steroids in those with COVID-19 and ARDS. However, the guidelines also note that, because of the very low quality of the evidence, some experts on the panel preferred not to issue a pro-steroids recommendation at all until higher-quality evidence becomes available. Dr. Pickkers said he believes that the minority view should have prevailed. Moreover, current COVID-19 guidance from the World Health Organization is at odds with the Surviving Sepsis Campaign recommendations; the WHO advises against corticosteroids unless the treatment is indicated for a reason other than immunomodulation, he noted.

The evidence in favor of steroids in an effort to blunt the immune response in COVID patients with ARDS is based largely upon a single small, retrospective, non–peer-reviewed report that 5-7 days of treatment with 1-2 mg/kg per day of methylprednisolone was associated with shortened fever duration and need for supplemental oxygen.

The evidence against steroids for immunomodulation comes mainly from earlier studies of the SARS and MERS novel coronaviruses. For example, in a multicenter study of 309 patients with the MERS (Middle East respiratory syndrome) virus, those who received corticosteroids received no benefit and experienced delayed viral clearance (Am J Respir Crit Care Med. 2018 Mar 15;197[6]:757-67).

“The thing is, virtually all COVID-19 patients in the ICU fulfill the criteria for ARDS, so following the Surviving Sepsis Campaign guidelines would have far-reaching consequences,” Dr. Pickkers said.

Those consequences include a theoretic potential for serious harm arising from dampening the immune response at a point in the course of COVID-19 when the virus is still present, which could result in slowed viral clearance and prolonged viral shedding. Moreover so far no one has been able to identify a sweet spot in the disease course where the viral load has waned and the immune response is sufficiently early that intervention with corticosteroids might have an optimal benefit/risk ratio, he continued.

“My opinion is that at this moment there is no benefit at all for corticosteroids for immunomodulation in patients with COVID-19,” Dr. Pickkers said. “My personal recommendation, in contrast to the Surviving Sepsis Campaign recommendation, is not to use this therapy outside of a study.”

He added that randomized, controlled trials of corticosteroid therapy in critically ill patients with COVID-19 are ongoing in Europe and the United States, including the large RECOVERY study of dexamethasone in the United Kingdom.

As for the Surviving Sepsis Campaign recommendation to use corticosteroids to treat refractory shock in COVID-19, Dr. Pickkers dismissed this guidance as largely irrelevant. That’s because few patients with COVID-19 who need mechanical ventilation have refractory shock as evidenced by the need for a high infusion rate of norepinephrine. Anyway, he noted, that Surviving Sepsis recommendation is based upon extrapolation from evidence of benefit in bacterial septic shock patients, which he deemed to be of questionable relevance to the COVID-19 pandemic.
 

Attacking the fibroproliferative phase of ARDS

First off, Dr. Pickkers conceded, there is no evidence that treatment with corticosteroids to prevent lung fibrosis in COVID-19 patients with nonresolving ARDS is an effective strategy; the pandemic is simply too new at this point for the appropriate studies to have been done. But this much is known: Postmortem pathologic studies show fibroplastic proliferation is present in the lungs of COVID-19 patients, as in those who die of ARDS of other causes. Also, COVID-19 patients typically aren’t admitted to the ICU until day 11 or 12 after developing their first symptoms, so by the time they display indications that their ARDS is not resolving, the virus has typically left the scene; thus, there is little risk at that point that corticosteroids will promote viral proliferation. Additionally, studies in critically ill patients with nonresolving ARDS of other causes show clinically meaningful benefits for corticosteroid therapy.

Dr. Pickkers cited as “must reading” an analysis of five randomized trials of corticosteroid therapy in a total of 518 patients with acute lung injury ARDS of non–COVID-19 origin. The analysis by investigators at the University of Tennessee, Memphis, concluded that treatment resulted in clinically meaningful reductions in duration of mechanical ventilation and ICU length of stay. Moreover, in the 400 patients whose steroid therapy commenced before day 14 of ARDS, there was a statistically significant 22% reduction in risk of death, compared with patients in whom corticosteroids were started later (Intensive Care Med. 2008 Jan;34[1]:61-9).

Session cochair Jan De Waele, MD, PhD, struck a cautious note, remarking, “It’s my perception that we’re using the evidence that we’ve gathered in other conditions and are now trying to apply it in COVID-19. But quality data on patients with COVID-19 itself is pretty scare, and it’s really hard to say whether this disease behaves similarly to bacterial septic shock or to other viral infections.”

“We need more information about the use of corticosteroids in COVID-19, although I think a lot of people are using it at this moment,” added Dr. De Waele, a surgical intensivist at Ghent (Belgium) University.

That being said, he asked Dr. Pickkers when he considers using corticosteroids to prevent pulmonary fibrosis.

Dr. Pickkers said that when he notices that a COVID-19 patient’s lung compliance is worsening, that stiff lung is a clue that fibrosis is occurring and is having clinical consequences. “We also measure blood procollagen, a not very sensitive but moderately specific marker of fibroproliferation. If we see an increase in this biomarker and the lung mechanics are changing, then we do treat these patients with corticosteroids,” Dr. Pickkers replied.

He and his colleagues try to start steroids before day 14 of ARDS, and they continue treatment for longer than 7 days in order to prevent a rebound inflammatory response upon treatment discontinuation. They also avoid using neuromuscular agents and engage in meticulous infection surveillance in order to minimize potential complications of corticosteroid therapy in the ICU.

Dr. Pickkers reported having no financial conflicts regarding his presentation.

[email protected]

Three main reasons have been put forth for using corticosteroids in critically ill patients with COVID-19, but only one – the hope of preventing lung fibrosis in patients with unresolved acute respiratory distress syndrome – is reasonable to employ now outside of formal randomized trials, Peter Pickkers, MD, PhD, asserted at a webinar on COVID-19 sponsored by the European Society of Intensive Care Medicine.

The most commonly invoked rationale for giving steroids in patients with severe COVID-19 is to modulate the destructive inflammatory immune response that occurs with advancing disease. Another justification cited for giving steroids is to treat suspected adrenal insufficiency in those with refractory shock. Of note, both practices are endorsed in the recent Surviving Sepsis Campaign guidelines on management of critically ill patients with COVID-19 (Intensive Care Med. 2020 May;46[5]:854-87).

But those recommendations – numbers 22 and 42 out of a total of 50 recommendations included in the guidelines – should never have been made, according to Dr. Pickkers, professor of experimental intensive care medicine at Radboud University Medical Center in Nijmegen, the Netherlands.
 

Dueling guidelines

The Surviving Sepsis Campaign guidelines, which were developed by a panel comprising 36 experts in 12 countries, are quite frank in conceding that the guidance in favor of corticosteroids are weak recommendations based on low-quality evidence.

The guidelines recommend against using corticosteroids to try to modulate the immune system in mechanically ventilated COVID-19 patients without acute respiratory distress syndrome (ARDS), but do recommend steroids in those with COVID-19 and ARDS. However, the guidelines also note that, because of the very low quality of the evidence, some experts on the panel preferred not to issue a pro-steroids recommendation at all until higher-quality evidence becomes available. Dr. Pickkers said he believes that the minority view should have prevailed. Moreover, current COVID-19 guidance from the World Health Organization is at odds with the Surviving Sepsis Campaign recommendations; the WHO advises against corticosteroids unless the treatment is indicated for a reason other than immunomodulation, he noted.

The evidence in favor of steroids in an effort to blunt the immune response in COVID patients with ARDS is based largely upon a single small, retrospective, non–peer-reviewed report that 5-7 days of treatment with 1-2 mg/kg per day of methylprednisolone was associated with shortened fever duration and need for supplemental oxygen.

The evidence against steroids for immunomodulation comes mainly from earlier studies of the SARS and MERS novel coronaviruses. For example, in a multicenter study of 309 patients with the MERS (Middle East respiratory syndrome) virus, those who received corticosteroids received no benefit and experienced delayed viral clearance (Am J Respir Crit Care Med. 2018 Mar 15;197[6]:757-67).

“The thing is, virtually all COVID-19 patients in the ICU fulfill the criteria for ARDS, so following the Surviving Sepsis Campaign guidelines would have far-reaching consequences,” Dr. Pickkers said.

Those consequences include a theoretic potential for serious harm arising from dampening the immune response at a point in the course of COVID-19 when the virus is still present, which could result in slowed viral clearance and prolonged viral shedding. Moreover so far no one has been able to identify a sweet spot in the disease course where the viral load has waned and the immune response is sufficiently early that intervention with corticosteroids might have an optimal benefit/risk ratio, he continued.

“My opinion is that at this moment there is no benefit at all for corticosteroids for immunomodulation in patients with COVID-19,” Dr. Pickkers said. “My personal recommendation, in contrast to the Surviving Sepsis Campaign recommendation, is not to use this therapy outside of a study.”

He added that randomized, controlled trials of corticosteroid therapy in critically ill patients with COVID-19 are ongoing in Europe and the United States, including the large RECOVERY study of dexamethasone in the United Kingdom.

As for the Surviving Sepsis Campaign recommendation to use corticosteroids to treat refractory shock in COVID-19, Dr. Pickkers dismissed this guidance as largely irrelevant. That’s because few patients with COVID-19 who need mechanical ventilation have refractory shock as evidenced by the need for a high infusion rate of norepinephrine. Anyway, he noted, that Surviving Sepsis recommendation is based upon extrapolation from evidence of benefit in bacterial septic shock patients, which he deemed to be of questionable relevance to the COVID-19 pandemic.
 

Attacking the fibroproliferative phase of ARDS

First off, Dr. Pickkers conceded, there is no evidence that treatment with corticosteroids to prevent lung fibrosis in COVID-19 patients with nonresolving ARDS is an effective strategy; the pandemic is simply too new at this point for the appropriate studies to have been done. But this much is known: Postmortem pathologic studies show fibroplastic proliferation is present in the lungs of COVID-19 patients, as in those who die of ARDS of other causes. Also, COVID-19 patients typically aren’t admitted to the ICU until day 11 or 12 after developing their first symptoms, so by the time they display indications that their ARDS is not resolving, the virus has typically left the scene; thus, there is little risk at that point that corticosteroids will promote viral proliferation. Additionally, studies in critically ill patients with nonresolving ARDS of other causes show clinically meaningful benefits for corticosteroid therapy.

Dr. Pickkers cited as “must reading” an analysis of five randomized trials of corticosteroid therapy in a total of 518 patients with acute lung injury ARDS of non–COVID-19 origin. The analysis by investigators at the University of Tennessee, Memphis, concluded that treatment resulted in clinically meaningful reductions in duration of mechanical ventilation and ICU length of stay. Moreover, in the 400 patients whose steroid therapy commenced before day 14 of ARDS, there was a statistically significant 22% reduction in risk of death, compared with patients in whom corticosteroids were started later (Intensive Care Med. 2008 Jan;34[1]:61-9).

Session cochair Jan De Waele, MD, PhD, struck a cautious note, remarking, “It’s my perception that we’re using the evidence that we’ve gathered in other conditions and are now trying to apply it in COVID-19. But quality data on patients with COVID-19 itself is pretty scare, and it’s really hard to say whether this disease behaves similarly to bacterial septic shock or to other viral infections.”

“We need more information about the use of corticosteroids in COVID-19, although I think a lot of people are using it at this moment,” added Dr. De Waele, a surgical intensivist at Ghent (Belgium) University.

That being said, he asked Dr. Pickkers when he considers using corticosteroids to prevent pulmonary fibrosis.

Dr. Pickkers said that when he notices that a COVID-19 patient’s lung compliance is worsening, that stiff lung is a clue that fibrosis is occurring and is having clinical consequences. “We also measure blood procollagen, a not very sensitive but moderately specific marker of fibroproliferation. If we see an increase in this biomarker and the lung mechanics are changing, then we do treat these patients with corticosteroids,” Dr. Pickkers replied.

He and his colleagues try to start steroids before day 14 of ARDS, and they continue treatment for longer than 7 days in order to prevent a rebound inflammatory response upon treatment discontinuation. They also avoid using neuromuscular agents and engage in meticulous infection surveillance in order to minimize potential complications of corticosteroid therapy in the ICU.

Dr. Pickkers reported having no financial conflicts regarding his presentation.

[email protected]

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