Federal Practitioner

Further data suggesting that a lower dose of rituximab seems to offer similar effectiveness with a better safety profile than higher doses commonly used in multiple sclerosis (MS), according to a new observational study. “We showed similar numbers of relapses, MRI new/active lesions, and effects on disability with a higher and lower dose of rituximab over a median follow of 16 months,” said lead author, Luciana Midaglia, MD, Multiple Sclerosis Centre of Catalonia (Cemcat) at Vall d’Hebron University Hospital, Barcelona. “But adverse effects – particularly frequency of infection – were increased in the high-dose group.”

Dr. Midaglia presented the findings at the recent Joint European Committee for Treatment and Research in Multiple Sclerosis–Americas Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS-ACTRIMS) 2020, this year known as MSVirtual2020.

“There haven’t been large studies of rituximab in MS as the company [Genentech/Roche] prioritized development of ocrelizumab over rituximab,” she explained. Rituximab has, therefore, never been approved for this indication. But it is available for several other conditions, and it is often used off label for MS.

“Although we now have a lot of experience with rituximab in MS, a dosage regimen has not been standardized,” Dr. Midaglia noted.

The current study was conducted to compare the efficacy and safety of two different dosage regimens of rituximab used at two different Catalan MS centers.

In the Barcelona center, 249 patients received a regimen of 2 g IV for the first three 6-month cycles followed by 1 g every 6 months thereafter (higher-dose group). In the Girona center, 54 patients received just one loading dose of 2 g followed by 500 mg every 6 months thereafter (lower-dose group).

Patients were followed up clinically every 6 months, and MRI brain scans were performed at baseline and yearly thereafter. Blood samples for safety and B cell/immunoglobulin monitoring were drawn at 3 months after rituximab infusions.

Results showed that the annualized relapse rate reduced by 87% (from 0.4 to 0.05; P < .001) in the higher-dose cohort, and by 90% (from 0.31 to 0.03; P = .018) in the lower-dose cohort.

The Expanded Disability Status Scale score remained stable or improved in 83% of the higher-dose group versus 72% of the lower-dose group (P = .09).

Contrast-enhancing lesions were reduced by 92% by 12 months and by 100% by 36 months in the higher-dose group and by 81% and 100%, respectively, in the lower-dose group.

New T2 lesions were present in 19% of patients at 12 months and in 12% at 36 months in the higher-dose group and in 16% and 0%, respectively, in the lower-dose group.

Reductions in B cell levels were similar with both doses. However, a reduced rate of adverse effects, mainly infections, was seen in the lower-dose group.

Infections were reported in 7.2% of the higher-dose group and 3.7% of the lower-dose group at 1 year, in 9.7% versus 0% in the second year, and in 9.7% versus 0% in the third year. Urinary tract infections, followed by respiratory infections, were the most prevalent.

A randomized phase 3 study is now underway testing an even lower dose of rituximab. The trial, known as RIDOSE-MS, is comparing maintenance doses of 500 mg every 6 months and 500 mg every 12 months.

Dr. Midaglia said that most centers are using higher doses of rituximab – similar to the Barcelona cohort in this study.

“After this study, we will we now start a new protocol and use the lower dose for all MS patients,” she said.

She reported that her hospital has been using rituximab extensively in MS.

“There were delays to ocrelizumab being introduced in Spain, and while we were waiting, we started using rituximab,” she said. “We believe it is similarly effective to ocrelizumab. It has exactly the same mechanism of action. The only difference is that rituximab is a chimeric antibody while ocrelizumab is fully humanized.”

While rituximab has not had the validation of a full phase 3 trial, she added, “there are data available from several smaller studies and we feel we have learned how to use it in the real world, but we don’t have an approved dosage schedule. We started off using the dose approved for use in rheumatological and hematological conditions.”

Now that ocrelizumab is approved, Dr. Midaglia said they are using that drug for the patients who meet the approved criteria, but there are many patients who don’t qualify.

“For example, in progressive MS, ocrelizumab has quite a narrow indication – it is not reimbursed for patients without any inflammatory activity. So for these patients, we tend to use rituximab,” she noted.

“While there is no good data on its efficacy in these patients, we believe it has some effect and there is no other option at present. Rituximab is an inexpensive drug and has a long safety record in other conditions, so we feel it’s worth a try,” Dr. Midaglia concluded. “And now we have better data on the optimal dosage.”

Commenting on the study, Daniel Ontaneda, MD, comoderator of the session at which the study was presented, said: “Rituximab is not an [Food and Drug Administration]–approved medication for MS, but it has been used in clinical practice quite extensively in the U.S. and also in Europe. The study is of interest as it showed that the lower dose of rituximab achieved good control of disease activity.”

Dr. Ontaneda, a neurologist at the Mellen Center for MS at the Cleveland Clinic, Ohio, added: “Many centers have been using lower doses or less frequent infusions and this study supports this practice. Some degree of residual confounding in the study in the differences in side effects may be related to the two different sites, but overall I think these results add to the real-world observational data now available for anti-CD20 therapies.”

Dr. Midaglia reported receiving travel funding from Genzyme, Roche, Biogen Idec, and Novartis, and personal fees for lectures from Roche.
 

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

Further data suggesting that a lower dose of rituximab seems to offer similar effectiveness with a better safety profile than higher doses commonly used in multiple sclerosis (MS), according to a new observational study. “We showed similar numbers of relapses, MRI new/active lesions, and effects on disability with a higher and lower dose of rituximab over a median follow of 16 months,” said lead author, Luciana Midaglia, MD, Multiple Sclerosis Centre of Catalonia (Cemcat) at Vall d’Hebron University Hospital, Barcelona. “But adverse effects – particularly frequency of infection – were increased in the high-dose group.”

Dr. Midaglia presented the findings at the recent Joint European Committee for Treatment and Research in Multiple Sclerosis–Americas Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS-ACTRIMS) 2020, this year known as MSVirtual2020.

“There haven’t been large studies of rituximab in MS as the company [Genentech/Roche] prioritized development of ocrelizumab over rituximab,” she explained. Rituximab has, therefore, never been approved for this indication. But it is available for several other conditions, and it is often used off label for MS.

“Although we now have a lot of experience with rituximab in MS, a dosage regimen has not been standardized,” Dr. Midaglia noted.

The current study was conducted to compare the efficacy and safety of two different dosage regimens of rituximab used at two different Catalan MS centers.

In the Barcelona center, 249 patients received a regimen of 2 g IV for the first three 6-month cycles followed by 1 g every 6 months thereafter (higher-dose group). In the Girona center, 54 patients received just one loading dose of 2 g followed by 500 mg every 6 months thereafter (lower-dose group).

Patients were followed up clinically every 6 months, and MRI brain scans were performed at baseline and yearly thereafter. Blood samples for safety and B cell/immunoglobulin monitoring were drawn at 3 months after rituximab infusions.

Results showed that the annualized relapse rate reduced by 87% (from 0.4 to 0.05; P < .001) in the higher-dose cohort, and by 90% (from 0.31 to 0.03; P = .018) in the lower-dose cohort.

The Expanded Disability Status Scale score remained stable or improved in 83% of the higher-dose group versus 72% of the lower-dose group (P = .09).

Contrast-enhancing lesions were reduced by 92% by 12 months and by 100% by 36 months in the higher-dose group and by 81% and 100%, respectively, in the lower-dose group.

New T2 lesions were present in 19% of patients at 12 months and in 12% at 36 months in the higher-dose group and in 16% and 0%, respectively, in the lower-dose group.

Reductions in B cell levels were similar with both doses. However, a reduced rate of adverse effects, mainly infections, was seen in the lower-dose group.

Infections were reported in 7.2% of the higher-dose group and 3.7% of the lower-dose group at 1 year, in 9.7% versus 0% in the second year, and in 9.7% versus 0% in the third year. Urinary tract infections, followed by respiratory infections, were the most prevalent.

A randomized phase 3 study is now underway testing an even lower dose of rituximab. The trial, known as RIDOSE-MS, is comparing maintenance doses of 500 mg every 6 months and 500 mg every 12 months.

Dr. Midaglia said that most centers are using higher doses of rituximab – similar to the Barcelona cohort in this study.

“After this study, we will we now start a new protocol and use the lower dose for all MS patients,” she said.

She reported that her hospital has been using rituximab extensively in MS.

“There were delays to ocrelizumab being introduced in Spain, and while we were waiting, we started using rituximab,” she said. “We believe it is similarly effective to ocrelizumab. It has exactly the same mechanism of action. The only difference is that rituximab is a chimeric antibody while ocrelizumab is fully humanized.”

While rituximab has not had the validation of a full phase 3 trial, she added, “there are data available from several smaller studies and we feel we have learned how to use it in the real world, but we don’t have an approved dosage schedule. We started off using the dose approved for use in rheumatological and hematological conditions.”

Now that ocrelizumab is approved, Dr. Midaglia said they are using that drug for the patients who meet the approved criteria, but there are many patients who don’t qualify.

“For example, in progressive MS, ocrelizumab has quite a narrow indication – it is not reimbursed for patients without any inflammatory activity. So for these patients, we tend to use rituximab,” she noted.

“While there is no good data on its efficacy in these patients, we believe it has some effect and there is no other option at present. Rituximab is an inexpensive drug and has a long safety record in other conditions, so we feel it’s worth a try,” Dr. Midaglia concluded. “And now we have better data on the optimal dosage.”

Commenting on the study, Daniel Ontaneda, MD, comoderator of the session at which the study was presented, said: “Rituximab is not an [Food and Drug Administration]–approved medication for MS, but it has been used in clinical practice quite extensively in the U.S. and also in Europe. The study is of interest as it showed that the lower dose of rituximab achieved good control of disease activity.”

Dr. Ontaneda, a neurologist at the Mellen Center for MS at the Cleveland Clinic, Ohio, added: “Many centers have been using lower doses or less frequent infusions and this study supports this practice. Some degree of residual confounding in the study in the differences in side effects may be related to the two different sites, but overall I think these results add to the real-world observational data now available for anti-CD20 therapies.”

Dr. Midaglia reported receiving travel funding from Genzyme, Roche, Biogen Idec, and Novartis, and personal fees for lectures from Roche.
 

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

Further data suggesting that a lower dose of rituximab seems to offer similar effectiveness with a better safety profile than higher doses commonly used in multiple sclerosis (MS), according to a new observational study. “We showed similar numbers of relapses, MRI new/active lesions, and effects on disability with a higher and lower dose of rituximab over a median follow of 16 months,” said lead author, Luciana Midaglia, MD, Multiple Sclerosis Centre of Catalonia (Cemcat) at Vall d’Hebron University Hospital, Barcelona. “But adverse effects – particularly frequency of infection – were increased in the high-dose group.”

Dr. Midaglia presented the findings at the recent Joint European Committee for Treatment and Research in Multiple Sclerosis–Americas Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS-ACTRIMS) 2020, this year known as MSVirtual2020.

“There haven’t been large studies of rituximab in MS as the company [Genentech/Roche] prioritized development of ocrelizumab over rituximab,” she explained. Rituximab has, therefore, never been approved for this indication. But it is available for several other conditions, and it is often used off label for MS.

“Although we now have a lot of experience with rituximab in MS, a dosage regimen has not been standardized,” Dr. Midaglia noted.

The current study was conducted to compare the efficacy and safety of two different dosage regimens of rituximab used at two different Catalan MS centers.

In the Barcelona center, 249 patients received a regimen of 2 g IV for the first three 6-month cycles followed by 1 g every 6 months thereafter (higher-dose group). In the Girona center, 54 patients received just one loading dose of 2 g followed by 500 mg every 6 months thereafter (lower-dose group).

Patients were followed up clinically every 6 months, and MRI brain scans were performed at baseline and yearly thereafter. Blood samples for safety and B cell/immunoglobulin monitoring were drawn at 3 months after rituximab infusions.

Results showed that the annualized relapse rate reduced by 87% (from 0.4 to 0.05; P < .001) in the higher-dose cohort, and by 90% (from 0.31 to 0.03; P = .018) in the lower-dose cohort.

The Expanded Disability Status Scale score remained stable or improved in 83% of the higher-dose group versus 72% of the lower-dose group (P = .09).

Contrast-enhancing lesions were reduced by 92% by 12 months and by 100% by 36 months in the higher-dose group and by 81% and 100%, respectively, in the lower-dose group.

New T2 lesions were present in 19% of patients at 12 months and in 12% at 36 months in the higher-dose group and in 16% and 0%, respectively, in the lower-dose group.

Reductions in B cell levels were similar with both doses. However, a reduced rate of adverse effects, mainly infections, was seen in the lower-dose group.

Infections were reported in 7.2% of the higher-dose group and 3.7% of the lower-dose group at 1 year, in 9.7% versus 0% in the second year, and in 9.7% versus 0% in the third year. Urinary tract infections, followed by respiratory infections, were the most prevalent.

A randomized phase 3 study is now underway testing an even lower dose of rituximab. The trial, known as RIDOSE-MS, is comparing maintenance doses of 500 mg every 6 months and 500 mg every 12 months.

Dr. Midaglia said that most centers are using higher doses of rituximab – similar to the Barcelona cohort in this study.

“After this study, we will we now start a new protocol and use the lower dose for all MS patients,” she said.

She reported that her hospital has been using rituximab extensively in MS.

“There were delays to ocrelizumab being introduced in Spain, and while we were waiting, we started using rituximab,” she said. “We believe it is similarly effective to ocrelizumab. It has exactly the same mechanism of action. The only difference is that rituximab is a chimeric antibody while ocrelizumab is fully humanized.”

While rituximab has not had the validation of a full phase 3 trial, she added, “there are data available from several smaller studies and we feel we have learned how to use it in the real world, but we don’t have an approved dosage schedule. We started off using the dose approved for use in rheumatological and hematological conditions.”

Now that ocrelizumab is approved, Dr. Midaglia said they are using that drug for the patients who meet the approved criteria, but there are many patients who don’t qualify.

“For example, in progressive MS, ocrelizumab has quite a narrow indication – it is not reimbursed for patients without any inflammatory activity. So for these patients, we tend to use rituximab,” she noted.

“While there is no good data on its efficacy in these patients, we believe it has some effect and there is no other option at present. Rituximab is an inexpensive drug and has a long safety record in other conditions, so we feel it’s worth a try,” Dr. Midaglia concluded. “And now we have better data on the optimal dosage.”

Commenting on the study, Daniel Ontaneda, MD, comoderator of the session at which the study was presented, said: “Rituximab is not an [Food and Drug Administration]–approved medication for MS, but it has been used in clinical practice quite extensively in the U.S. and also in Europe. The study is of interest as it showed that the lower dose of rituximab achieved good control of disease activity.”

Dr. Ontaneda, a neurologist at the Mellen Center for MS at the Cleveland Clinic, Ohio, added: “Many centers have been using lower doses or less frequent infusions and this study supports this practice. Some degree of residual confounding in the study in the differences in side effects may be related to the two different sites, but overall I think these results add to the real-world observational data now available for anti-CD20 therapies.”

Dr. Midaglia reported receiving travel funding from Genzyme, Roche, Biogen Idec, and Novartis, and personal fees for lectures from Roche.
 

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

Johnson & Johnson (J&J) on Wednesday said it advanced into phase 3 testing of its COVID-19 vaccine candidate, which uses the same technology as an Ebola vaccine already approved by European regulators.

The National Institute of Allergy and Infectious Diseases, which is aiding Johnson & Johnson with development, described this in a news release as the fourth phase 3 clinical trial of evaluating an investigational vaccine for coronavirus disease.

This NIAID tally tracks products likely to be presented soon for Food and Drug Administration approval. (The World Health Organization’s COVID vaccine tracker lists nine candidates as having reached this stage, including products developed in Russia and China.)

As many as 60,000 volunteers will be enrolled in the trial, with about 215 clinical research sites expected to participate, NIAID said. The vaccine will be tested in the United States and abroad.

The start of this test, known as the ENSEMBLE trial, follows positive results from a Phase 1/2a clinical study, which involved a single vaccination. The results of this study have been submitted to medRxiv and are set to be published online imminently.

New Brunswick, N.J–based J&J said it intends to offer the vaccine on “a not-for-profit basis for emergency pandemic use.” If testing proceeds well, J&J might seek an emergency use clearance for the vaccine, which could possibly allow the first batches to be made available in early 2021.

J&J’s vaccine is unusual in that it will be tested based on a single dose, while other advanced candidates have been tested in two-dose regimens.

J&J on Wednesday also released the study protocol for its phase 3 test. The developers of the other late-stage COVID vaccine candidates also have done this, as reported by Medscape Medical News. Because of the great interest in the COVID vaccine, the American Medical Association had last month asked the FDA to keep physicians informed of their COVID-19 vaccine review process.
 

Trials and tribulations

One of these experimental COVID vaccines already has had a setback in phase 3 testing, which is a fairly routine occurrence in drug development. But with a pandemic still causing deaths and disrupting lives around the world, there has been intense interest in each step of the effort to develop a COVID vaccine.

AstraZeneca PLC earlier this month announced a temporary cessation of all their coronavirus vaccine trials to investigate an “unexplained illness” that arose in a participant, as reported by Medscape Medical News.

On September 12, AstraZeneca announced that clinical trials for the AZD1222, which it developed with Oxford University, had resumed in the United Kingdom. On Wednesday, CNBC said Health and Human Services Secretary Alex Azar told the news station that AstraZeneca’s late-stage coronavirus vaccine trial in the United States remains on hold until safety concerns are resolved, a critical issue with all the fast-track COVID vaccines now being tested.

“Look at the AstraZeneca program, phase 3 clinical trial, a lot of hope. [A] single serious adverse event report in the United Kingdom, global shutdown, and [a] hold of the clinical trials,” Mr. Azar told CNBC.

The New York Times has reported on concerns stemming from serious neurologic illnesses in two participants, both women, who received AstraZeneca’s experimental vaccine in Britain.

The Senate Health, Education, Labor and Pensions Committee on Wednesday separately held a hearing with the leaders of the FDA and the Centers of Disease Control and Prevention, allowing an airing of lawmakers’ concerns about a potential rush to approve a COVID vaccine.
 

Details of J&J trial

The J&J trial is designed primarily to determine if the investigational vaccine can prevent moderate to severe COVID-19 after a single dose. It also is designed to examine whether the vaccine can prevent COVID-19 requiring medical intervention and if the vaccine can prevent milder cases of COVID-19 and asymptomatic SARS-CoV-2 infection, NIAID said.

Principal investigators for the phase 3 trial of the J & J vaccine are Paul A. Goepfert, MD, director of the Alabama Vaccine Research Clinic at the University of Alabama in Birmingham; Beatriz Grinsztejn, MD, PhD, director of the Laboratory of Clinical Research on HIV/AIDS at the Evandro Chagas National Institute of Infectious Diseases-Oswaldo Cruz Foundation in Rio de Janeiro, Brazil; and Glenda E. Gray, MBBCh, president and chief executive officer of the South African Medical Research Council and coprincipal investigator of the HIV Vaccine Trials Network.

This article first appeared on Medscape.com.

Johnson & Johnson (J&J) on Wednesday said it advanced into phase 3 testing of its COVID-19 vaccine candidate, which uses the same technology as an Ebola vaccine already approved by European regulators.

The National Institute of Allergy and Infectious Diseases, which is aiding Johnson & Johnson with development, described this in a news release as the fourth phase 3 clinical trial of evaluating an investigational vaccine for coronavirus disease.

This NIAID tally tracks products likely to be presented soon for Food and Drug Administration approval. (The World Health Organization’s COVID vaccine tracker lists nine candidates as having reached this stage, including products developed in Russia and China.)

As many as 60,000 volunteers will be enrolled in the trial, with about 215 clinical research sites expected to participate, NIAID said. The vaccine will be tested in the United States and abroad.

The start of this test, known as the ENSEMBLE trial, follows positive results from a Phase 1/2a clinical study, which involved a single vaccination. The results of this study have been submitted to medRxiv and are set to be published online imminently.

New Brunswick, N.J–based J&J said it intends to offer the vaccine on “a not-for-profit basis for emergency pandemic use.” If testing proceeds well, J&J might seek an emergency use clearance for the vaccine, which could possibly allow the first batches to be made available in early 2021.

J&J’s vaccine is unusual in that it will be tested based on a single dose, while other advanced candidates have been tested in two-dose regimens.

J&J on Wednesday also released the study protocol for its phase 3 test. The developers of the other late-stage COVID vaccine candidates also have done this, as reported by Medscape Medical News. Because of the great interest in the COVID vaccine, the American Medical Association had last month asked the FDA to keep physicians informed of their COVID-19 vaccine review process.
 

Trials and tribulations

One of these experimental COVID vaccines already has had a setback in phase 3 testing, which is a fairly routine occurrence in drug development. But with a pandemic still causing deaths and disrupting lives around the world, there has been intense interest in each step of the effort to develop a COVID vaccine.

AstraZeneca PLC earlier this month announced a temporary cessation of all their coronavirus vaccine trials to investigate an “unexplained illness” that arose in a participant, as reported by Medscape Medical News.

On September 12, AstraZeneca announced that clinical trials for the AZD1222, which it developed with Oxford University, had resumed in the United Kingdom. On Wednesday, CNBC said Health and Human Services Secretary Alex Azar told the news station that AstraZeneca’s late-stage coronavirus vaccine trial in the United States remains on hold until safety concerns are resolved, a critical issue with all the fast-track COVID vaccines now being tested.

“Look at the AstraZeneca program, phase 3 clinical trial, a lot of hope. [A] single serious adverse event report in the United Kingdom, global shutdown, and [a] hold of the clinical trials,” Mr. Azar told CNBC.

The New York Times has reported on concerns stemming from serious neurologic illnesses in two participants, both women, who received AstraZeneca’s experimental vaccine in Britain.

The Senate Health, Education, Labor and Pensions Committee on Wednesday separately held a hearing with the leaders of the FDA and the Centers of Disease Control and Prevention, allowing an airing of lawmakers’ concerns about a potential rush to approve a COVID vaccine.
 

Details of J&J trial

The J&J trial is designed primarily to determine if the investigational vaccine can prevent moderate to severe COVID-19 after a single dose. It also is designed to examine whether the vaccine can prevent COVID-19 requiring medical intervention and if the vaccine can prevent milder cases of COVID-19 and asymptomatic SARS-CoV-2 infection, NIAID said.

Principal investigators for the phase 3 trial of the J & J vaccine are Paul A. Goepfert, MD, director of the Alabama Vaccine Research Clinic at the University of Alabama in Birmingham; Beatriz Grinsztejn, MD, PhD, director of the Laboratory of Clinical Research on HIV/AIDS at the Evandro Chagas National Institute of Infectious Diseases-Oswaldo Cruz Foundation in Rio de Janeiro, Brazil; and Glenda E. Gray, MBBCh, president and chief executive officer of the South African Medical Research Council and coprincipal investigator of the HIV Vaccine Trials Network.

This article first appeared on Medscape.com.

Johnson & Johnson (J&J) on Wednesday said it advanced into phase 3 testing of its COVID-19 vaccine candidate, which uses the same technology as an Ebola vaccine already approved by European regulators.

The National Institute of Allergy and Infectious Diseases, which is aiding Johnson & Johnson with development, described this in a news release as the fourth phase 3 clinical trial of evaluating an investigational vaccine for coronavirus disease.

This NIAID tally tracks products likely to be presented soon for Food and Drug Administration approval. (The World Health Organization’s COVID vaccine tracker lists nine candidates as having reached this stage, including products developed in Russia and China.)

As many as 60,000 volunteers will be enrolled in the trial, with about 215 clinical research sites expected to participate, NIAID said. The vaccine will be tested in the United States and abroad.

The start of this test, known as the ENSEMBLE trial, follows positive results from a Phase 1/2a clinical study, which involved a single vaccination. The results of this study have been submitted to medRxiv and are set to be published online imminently.

New Brunswick, N.J–based J&J said it intends to offer the vaccine on “a not-for-profit basis for emergency pandemic use.” If testing proceeds well, J&J might seek an emergency use clearance for the vaccine, which could possibly allow the first batches to be made available in early 2021.

J&J’s vaccine is unusual in that it will be tested based on a single dose, while other advanced candidates have been tested in two-dose regimens.

J&J on Wednesday also released the study protocol for its phase 3 test. The developers of the other late-stage COVID vaccine candidates also have done this, as reported by Medscape Medical News. Because of the great interest in the COVID vaccine, the American Medical Association had last month asked the FDA to keep physicians informed of their COVID-19 vaccine review process.
 

Trials and tribulations

One of these experimental COVID vaccines already has had a setback in phase 3 testing, which is a fairly routine occurrence in drug development. But with a pandemic still causing deaths and disrupting lives around the world, there has been intense interest in each step of the effort to develop a COVID vaccine.

AstraZeneca PLC earlier this month announced a temporary cessation of all their coronavirus vaccine trials to investigate an “unexplained illness” that arose in a participant, as reported by Medscape Medical News.

On September 12, AstraZeneca announced that clinical trials for the AZD1222, which it developed with Oxford University, had resumed in the United Kingdom. On Wednesday, CNBC said Health and Human Services Secretary Alex Azar told the news station that AstraZeneca’s late-stage coronavirus vaccine trial in the United States remains on hold until safety concerns are resolved, a critical issue with all the fast-track COVID vaccines now being tested.

“Look at the AstraZeneca program, phase 3 clinical trial, a lot of hope. [A] single serious adverse event report in the United Kingdom, global shutdown, and [a] hold of the clinical trials,” Mr. Azar told CNBC.

The New York Times has reported on concerns stemming from serious neurologic illnesses in two participants, both women, who received AstraZeneca’s experimental vaccine in Britain.

The Senate Health, Education, Labor and Pensions Committee on Wednesday separately held a hearing with the leaders of the FDA and the Centers of Disease Control and Prevention, allowing an airing of lawmakers’ concerns about a potential rush to approve a COVID vaccine.
 

Details of J&J trial

The J&J trial is designed primarily to determine if the investigational vaccine can prevent moderate to severe COVID-19 after a single dose. It also is designed to examine whether the vaccine can prevent COVID-19 requiring medical intervention and if the vaccine can prevent milder cases of COVID-19 and asymptomatic SARS-CoV-2 infection, NIAID said.

Principal investigators for the phase 3 trial of the J & J vaccine are Paul A. Goepfert, MD, director of the Alabama Vaccine Research Clinic at the University of Alabama in Birmingham; Beatriz Grinsztejn, MD, PhD, director of the Laboratory of Clinical Research on HIV/AIDS at the Evandro Chagas National Institute of Infectious Diseases-Oswaldo Cruz Foundation in Rio de Janeiro, Brazil; and Glenda E. Gray, MBBCh, president and chief executive officer of the South African Medical Research Council and coprincipal investigator of the HIV Vaccine Trials Network.

This article first appeared on Medscape.com.

America has been struggling to understand its racial dynamics since the arrival of enslaved Africans more than 400 years ago. Today, with much of the world more polarized than ever, and certainly in our United States, there is a need for something to shift us from our fear and survival paranoid schizoid (us-vs.-them) position to an integrated form if we are to come out of this unusual democratic and societal unrest whole.

Courtesy Random House

Yet, we’ve never had the lexicon to adequately describe the sociopolitical dynamics rooted in race and racism and their power to shape the thinking of all who originate in this country and all who enter its self-made borders whether forcefully or voluntarily. Enter Isabel Wilkerson, a Pulitzer Prize–winning, former New York Times Chicago bureau chief, and author of “The Warmth of Other Suns: The Epic Story of America’s Great Migration” (New York: Random House, 2010) with her second book, “Caste: The Origins of Our Discontents” (New York: Random House, 2020).

Ms. Wilkerson quickly gets to work in an engaging storytelling style of weaving past to present with ideas she supports with letters from the past, historians’ impressions, research studies, and data. Her observations and research are bookended by the lead up to the 2016 presidential election and its aftermath on the one end, and the impending 2020 presidential election on the other. In her view, the reemergence of violence that has accelerated in the 21st century and the renewed commitment to promote white supremacy can be understood if we expand our view of race and racism to consider the enduring power of caste. For, in Ms. Wilkerson’s view, the fear of the 2042 U.S. census (which is predicted to reflect for the first time a non-White majority) is a driving force behind the dominant caste’s determination to maintain the status quo power dynamics in the United States.

In an effort to explain American’s racial hierarchy, Ms. Wilkerson explains the need for a new lexicon “that may sound like a foreign language,” but this is intentional on her part. She writes:

“To recalibrate how we see ourselves, I use language that may be more commonly associated with people in other cultures, to suggest a new way of understanding our hierarchy: Dominant caste, ruling majority, favored caste, or upper caste, instead of, or in addition to, white. Middle castes instead of, or in addition to, Asian or Latino. Subordinate caste, lowest caste, bottom caste, disfavored caste, historically stigmatized instead of African-American. Original, conquered, or indigenous peoples instead of, or in addition to, Native American. Marginalized people in addition to, or instead of, women of any race, or minorities of any kind.”

Early in the book Ms. Wilkerson anchors her argument in Rev. Dr. Martin Luther King Jr.’s sojourn to India. Rather than focus on the known history of Dr. King’s admiration of Mohandas Gandhi, Ms. Wilkerson directs our attention to Dr. King’s discovery of his connection to Dalits, those who had been considered “untouchables” until Bhimrao Ramji Ambedkar, the Indian economist, jurist, social reformer, and Dalit leader, fiercely and successfully advocated for a rebranding of his caste of origin; instead of “untouchables” they would be considered Dalits or “broken people.” Dr. King did not meet Mr. Ambedkar, who died 3 years before this journey, but Ms. Wilkerson writes that Dr. King acknowledged the kinship, “And he said unto himself, Yes, I am an untouchable, and every Negro in the United States is an untouchable.” The Dalits and Dr. King recognized in each other their shared positions as subordinates in a global caste system.

In answering the question about the difference between racism and casteism, Ms. Wilkerson writes:

“Because caste and race are interwoven in America, it can be hard to separate the two. ... Casteism is the investment in keeping the hierarchy as it is in order to maintain your own ranking, advantage, privilege, or to elevate yourself above others or to keep others beneath you.”

Reading “Caste: The Origins of Our Discontents” is akin to the experience of gaining relief after struggling for years with a chronic malady that has a fluctuating course: Under the surface is low-grade pain that is compartmentalized and often met with denial or gaslighting when symptoms and systems are reported to members of the dominant caste. Yet, when there are acute flare-ups and increasingly frequent deadly encounters, the defenses of denial are painfully revealed; structures are broken and sometimes burned down. This has been the clinical course of racism, particularly in the United States. In that vein, an early reaction while reading “Caste” might be comparable to hearing an interpretation that educates, clarifies, resonates, and lands perfectly on the right diagnosis at the right moment.
 

Approach proves clarifying

In conceptualizing the malady as one of caste, Ms. Wilkerson achieves several things simultaneously – she names the malady, thus providing a lexicon, describes its symptoms, and most importantly, in our opinion, shares some of the compelling data from her field studies. By focusing on India, Nazi Germany, and the United States, she describes how easily one system influences another in the global effort to maintain power among the privileged.

This is not a new way of conceptualizing racial hierarchy; however, what is truly persuasive is Ms. Wilkerson’s ability to weave her rigorous research, sociopolitical analysis, and cogent psychological insights and interpretations to explain the 400-year trajectory of racialized caste in the United States. She achieves this exigent task with beautiful prose that motivates the reader to return time and time again to learn gut-wrenching painful historical details. She summarizes truths that have been unearthed (again) about Germany, India, and, in particular, the United States during her research and travels around the world. In doing so, she provides vivid examples of racism layered on caste. Consider the following:

“The Nazis were impressed by the American custom of lynching its subordinate caste of African-Americans, having become aware of the ritual torture and mutilations that typically accompanied them. Hitler especially marveled at the American ‘knack for maintaining an air of robust innocence in the wake of mass death.’ ” Ms. Wilkerson informs us that Hitler sent emissaries to study America’s Jim Crow system and then imported some features to orchestrate the Holocaust in Nazi Germany.

Her most vivid example of internalized casteism is the experience of a Dalit scholar who still experiences anxiety and a corresponding sense of inadequacy in the presence of someone who is considered to be from a higher caste.

A painful account of interpersonal racism is captured as Ms. Wilkerson recounts her experience after a routine business flight from Chicago to Detroit. She details her difficulty leaving a rental car parking lot because she had become so disoriented after being profiled and accosted by Drug Enforcement Administration agents who had intercepted her in the airport terminal and followed her onto the airport shuttle bus as she attempted to reach her destination. She provides a description of “getting turned around in a parking lot that I had been to dozens of times, going in circles, not able to get out, not registering the signs to the exit, not seeing how to get to Interstate 94, when I knew full well how to get to I-94 after all the times I’d driven it. ... This was the thievery of caste, stealing the time and psychic resources of the marginalized, draining energy in an already uphill competition. They were not, like me, frozen and disoriented, trying to make sense of a public violation that seemed all the more menacing now that I could see it in full. The quiet mundanity of that terror has never left me, the scars outliving the cut.”

This account is consistent with the dissociative, disorienting dynamics of race-based trauma. Her experience is not uncommon and helps to explain the activism of those in the subordinate caste who have attained some measure of wealth, power, and influence, and are motivated to expend their resources (energy, time, fame, and/or wealth) to raise awareness about social and political injustices by calling out structural racism in medicine, protesting police use of force by taking a knee, boycotting sporting events, and even demanding that football stadiums be used as polling sites. At the end of the day, all of us who have “made it” know that when we leave our homes, our relegation to the subordinate caste determines how we are perceived and what landmines we must navigate to make it through the day and that determine whether we will make it home.

This tour de force work of art has the potential to be a game changer in the way that we think about racial polarization in the United States. It is hoped that this new language opens up a space that allows each of us to explore this hegemony while identifying our placement and actions we take to maintain it, for each of us undeniably has a position in this caste system.

Having this new lexicon summons to mind the reactions of patients who gain immediate relief from having their illnesses named. In the case of the U.S. malady that has gripped us all, Ms. Wilkerson reiterates the importance of naming the condition. She writes:

“Because, to truly understand America, we must open our eyes to the hidden work of a caste system that has gone unnamed but prevails among us to our collective detriment, to see that we have more in common with each other and with cultures that we might otherwise dismiss, and to summon the courage to consider that therein may lie the answers.”

The naming allows both doctor and patient to have greater insight, understanding its origins and course, as well as having hope that there is a remedy. Naming facilitates the space for a shift in thinking and implementation of treatment protocols, such as Nazi Germany’s “zero tolerance policy” of swastikas in comparison to the ongoing U.S. controversy about the display of Confederate symbols. At this point in history, we welcome a diagnosis that has the potential to shift us from these poles of dominant and subordinate, black and white, good and bad, toward integration and wholeness of the individual psyche and collective global community. This is similar to what Melanie Klein calls the depressive position. Ms. Wilkerson suggests, in relinquishing these polar splits, we increase our capacity to shift to a space where our psychic integration occurs and our inextricable interdependence and responsibility for one another are honored.
 

Dr. Dunlap is a psychiatrist and psychoanalyst, and clinical professor of psychiatry and behavioral sciences at George Washington University. She is interested in the management of “difference” – race, gender, ethnicity, and intersectionality – in dyadic relationships and group dynamics; and the impact of racism on interpersonal relationships in institutional structures. Dr. Dunlap practices in Washington and has no disclosures. Dr. Dennis is a clinical psychologist and psychoanalyst. Her interests are in gender and ethnic diversity, health equity, and supervision and training. Dr. Dennis practices in Washington and has no disclosures.

America has been struggling to understand its racial dynamics since the arrival of enslaved Africans more than 400 years ago. Today, with much of the world more polarized than ever, and certainly in our United States, there is a need for something to shift us from our fear and survival paranoid schizoid (us-vs.-them) position to an integrated form if we are to come out of this unusual democratic and societal unrest whole.

Courtesy Random House

Yet, we’ve never had the lexicon to adequately describe the sociopolitical dynamics rooted in race and racism and their power to shape the thinking of all who originate in this country and all who enter its self-made borders whether forcefully or voluntarily. Enter Isabel Wilkerson, a Pulitzer Prize–winning, former New York Times Chicago bureau chief, and author of “The Warmth of Other Suns: The Epic Story of America’s Great Migration” (New York: Random House, 2010) with her second book, “Caste: The Origins of Our Discontents” (New York: Random House, 2020).

Ms. Wilkerson quickly gets to work in an engaging storytelling style of weaving past to present with ideas she supports with letters from the past, historians’ impressions, research studies, and data. Her observations and research are bookended by the lead up to the 2016 presidential election and its aftermath on the one end, and the impending 2020 presidential election on the other. In her view, the reemergence of violence that has accelerated in the 21st century and the renewed commitment to promote white supremacy can be understood if we expand our view of race and racism to consider the enduring power of caste. For, in Ms. Wilkerson’s view, the fear of the 2042 U.S. census (which is predicted to reflect for the first time a non-White majority) is a driving force behind the dominant caste’s determination to maintain the status quo power dynamics in the United States.

In an effort to explain American’s racial hierarchy, Ms. Wilkerson explains the need for a new lexicon “that may sound like a foreign language,” but this is intentional on her part. She writes:

“To recalibrate how we see ourselves, I use language that may be more commonly associated with people in other cultures, to suggest a new way of understanding our hierarchy: Dominant caste, ruling majority, favored caste, or upper caste, instead of, or in addition to, white. Middle castes instead of, or in addition to, Asian or Latino. Subordinate caste, lowest caste, bottom caste, disfavored caste, historically stigmatized instead of African-American. Original, conquered, or indigenous peoples instead of, or in addition to, Native American. Marginalized people in addition to, or instead of, women of any race, or minorities of any kind.”

Early in the book Ms. Wilkerson anchors her argument in Rev. Dr. Martin Luther King Jr.’s sojourn to India. Rather than focus on the known history of Dr. King’s admiration of Mohandas Gandhi, Ms. Wilkerson directs our attention to Dr. King’s discovery of his connection to Dalits, those who had been considered “untouchables” until Bhimrao Ramji Ambedkar, the Indian economist, jurist, social reformer, and Dalit leader, fiercely and successfully advocated for a rebranding of his caste of origin; instead of “untouchables” they would be considered Dalits or “broken people.” Dr. King did not meet Mr. Ambedkar, who died 3 years before this journey, but Ms. Wilkerson writes that Dr. King acknowledged the kinship, “And he said unto himself, Yes, I am an untouchable, and every Negro in the United States is an untouchable.” The Dalits and Dr. King recognized in each other their shared positions as subordinates in a global caste system.

In answering the question about the difference between racism and casteism, Ms. Wilkerson writes:

“Because caste and race are interwoven in America, it can be hard to separate the two. ... Casteism is the investment in keeping the hierarchy as it is in order to maintain your own ranking, advantage, privilege, or to elevate yourself above others or to keep others beneath you.”

Reading “Caste: The Origins of Our Discontents” is akin to the experience of gaining relief after struggling for years with a chronic malady that has a fluctuating course: Under the surface is low-grade pain that is compartmentalized and often met with denial or gaslighting when symptoms and systems are reported to members of the dominant caste. Yet, when there are acute flare-ups and increasingly frequent deadly encounters, the defenses of denial are painfully revealed; structures are broken and sometimes burned down. This has been the clinical course of racism, particularly in the United States. In that vein, an early reaction while reading “Caste” might be comparable to hearing an interpretation that educates, clarifies, resonates, and lands perfectly on the right diagnosis at the right moment.
 

Approach proves clarifying

In conceptualizing the malady as one of caste, Ms. Wilkerson achieves several things simultaneously – she names the malady, thus providing a lexicon, describes its symptoms, and most importantly, in our opinion, shares some of the compelling data from her field studies. By focusing on India, Nazi Germany, and the United States, she describes how easily one system influences another in the global effort to maintain power among the privileged.

This is not a new way of conceptualizing racial hierarchy; however, what is truly persuasive is Ms. Wilkerson’s ability to weave her rigorous research, sociopolitical analysis, and cogent psychological insights and interpretations to explain the 400-year trajectory of racialized caste in the United States. She achieves this exigent task with beautiful prose that motivates the reader to return time and time again to learn gut-wrenching painful historical details. She summarizes truths that have been unearthed (again) about Germany, India, and, in particular, the United States during her research and travels around the world. In doing so, she provides vivid examples of racism layered on caste. Consider the following:

“The Nazis were impressed by the American custom of lynching its subordinate caste of African-Americans, having become aware of the ritual torture and mutilations that typically accompanied them. Hitler especially marveled at the American ‘knack for maintaining an air of robust innocence in the wake of mass death.’ ” Ms. Wilkerson informs us that Hitler sent emissaries to study America’s Jim Crow system and then imported some features to orchestrate the Holocaust in Nazi Germany.

Her most vivid example of internalized casteism is the experience of a Dalit scholar who still experiences anxiety and a corresponding sense of inadequacy in the presence of someone who is considered to be from a higher caste.

A painful account of interpersonal racism is captured as Ms. Wilkerson recounts her experience after a routine business flight from Chicago to Detroit. She details her difficulty leaving a rental car parking lot because she had become so disoriented after being profiled and accosted by Drug Enforcement Administration agents who had intercepted her in the airport terminal and followed her onto the airport shuttle bus as she attempted to reach her destination. She provides a description of “getting turned around in a parking lot that I had been to dozens of times, going in circles, not able to get out, not registering the signs to the exit, not seeing how to get to Interstate 94, when I knew full well how to get to I-94 after all the times I’d driven it. ... This was the thievery of caste, stealing the time and psychic resources of the marginalized, draining energy in an already uphill competition. They were not, like me, frozen and disoriented, trying to make sense of a public violation that seemed all the more menacing now that I could see it in full. The quiet mundanity of that terror has never left me, the scars outliving the cut.”

This account is consistent with the dissociative, disorienting dynamics of race-based trauma. Her experience is not uncommon and helps to explain the activism of those in the subordinate caste who have attained some measure of wealth, power, and influence, and are motivated to expend their resources (energy, time, fame, and/or wealth) to raise awareness about social and political injustices by calling out structural racism in medicine, protesting police use of force by taking a knee, boycotting sporting events, and even demanding that football stadiums be used as polling sites. At the end of the day, all of us who have “made it” know that when we leave our homes, our relegation to the subordinate caste determines how we are perceived and what landmines we must navigate to make it through the day and that determine whether we will make it home.

This tour de force work of art has the potential to be a game changer in the way that we think about racial polarization in the United States. It is hoped that this new language opens up a space that allows each of us to explore this hegemony while identifying our placement and actions we take to maintain it, for each of us undeniably has a position in this caste system.

Having this new lexicon summons to mind the reactions of patients who gain immediate relief from having their illnesses named. In the case of the U.S. malady that has gripped us all, Ms. Wilkerson reiterates the importance of naming the condition. She writes:

“Because, to truly understand America, we must open our eyes to the hidden work of a caste system that has gone unnamed but prevails among us to our collective detriment, to see that we have more in common with each other and with cultures that we might otherwise dismiss, and to summon the courage to consider that therein may lie the answers.”

The naming allows both doctor and patient to have greater insight, understanding its origins and course, as well as having hope that there is a remedy. Naming facilitates the space for a shift in thinking and implementation of treatment protocols, such as Nazi Germany’s “zero tolerance policy” of swastikas in comparison to the ongoing U.S. controversy about the display of Confederate symbols. At this point in history, we welcome a diagnosis that has the potential to shift us from these poles of dominant and subordinate, black and white, good and bad, toward integration and wholeness of the individual psyche and collective global community. This is similar to what Melanie Klein calls the depressive position. Ms. Wilkerson suggests, in relinquishing these polar splits, we increase our capacity to shift to a space where our psychic integration occurs and our inextricable interdependence and responsibility for one another are honored.
 

Dr. Dunlap is a psychiatrist and psychoanalyst, and clinical professor of psychiatry and behavioral sciences at George Washington University. She is interested in the management of “difference” – race, gender, ethnicity, and intersectionality – in dyadic relationships and group dynamics; and the impact of racism on interpersonal relationships in institutional structures. Dr. Dunlap practices in Washington and has no disclosures. Dr. Dennis is a clinical psychologist and psychoanalyst. Her interests are in gender and ethnic diversity, health equity, and supervision and training. Dr. Dennis practices in Washington and has no disclosures.

America has been struggling to understand its racial dynamics since the arrival of enslaved Africans more than 400 years ago. Today, with much of the world more polarized than ever, and certainly in our United States, there is a need for something to shift us from our fear and survival paranoid schizoid (us-vs.-them) position to an integrated form if we are to come out of this unusual democratic and societal unrest whole.

Courtesy Random House

Yet, we’ve never had the lexicon to adequately describe the sociopolitical dynamics rooted in race and racism and their power to shape the thinking of all who originate in this country and all who enter its self-made borders whether forcefully or voluntarily. Enter Isabel Wilkerson, a Pulitzer Prize–winning, former New York Times Chicago bureau chief, and author of “The Warmth of Other Suns: The Epic Story of America’s Great Migration” (New York: Random House, 2010) with her second book, “Caste: The Origins of Our Discontents” (New York: Random House, 2020).

Ms. Wilkerson quickly gets to work in an engaging storytelling style of weaving past to present with ideas she supports with letters from the past, historians’ impressions, research studies, and data. Her observations and research are bookended by the lead up to the 2016 presidential election and its aftermath on the one end, and the impending 2020 presidential election on the other. In her view, the reemergence of violence that has accelerated in the 21st century and the renewed commitment to promote white supremacy can be understood if we expand our view of race and racism to consider the enduring power of caste. For, in Ms. Wilkerson’s view, the fear of the 2042 U.S. census (which is predicted to reflect for the first time a non-White majority) is a driving force behind the dominant caste’s determination to maintain the status quo power dynamics in the United States.

In an effort to explain American’s racial hierarchy, Ms. Wilkerson explains the need for a new lexicon “that may sound like a foreign language,” but this is intentional on her part. She writes:

“To recalibrate how we see ourselves, I use language that may be more commonly associated with people in other cultures, to suggest a new way of understanding our hierarchy: Dominant caste, ruling majority, favored caste, or upper caste, instead of, or in addition to, white. Middle castes instead of, or in addition to, Asian or Latino. Subordinate caste, lowest caste, bottom caste, disfavored caste, historically stigmatized instead of African-American. Original, conquered, or indigenous peoples instead of, or in addition to, Native American. Marginalized people in addition to, or instead of, women of any race, or minorities of any kind.”

Early in the book Ms. Wilkerson anchors her argument in Rev. Dr. Martin Luther King Jr.’s sojourn to India. Rather than focus on the known history of Dr. King’s admiration of Mohandas Gandhi, Ms. Wilkerson directs our attention to Dr. King’s discovery of his connection to Dalits, those who had been considered “untouchables” until Bhimrao Ramji Ambedkar, the Indian economist, jurist, social reformer, and Dalit leader, fiercely and successfully advocated for a rebranding of his caste of origin; instead of “untouchables” they would be considered Dalits or “broken people.” Dr. King did not meet Mr. Ambedkar, who died 3 years before this journey, but Ms. Wilkerson writes that Dr. King acknowledged the kinship, “And he said unto himself, Yes, I am an untouchable, and every Negro in the United States is an untouchable.” The Dalits and Dr. King recognized in each other their shared positions as subordinates in a global caste system.

In answering the question about the difference between racism and casteism, Ms. Wilkerson writes:

“Because caste and race are interwoven in America, it can be hard to separate the two. ... Casteism is the investment in keeping the hierarchy as it is in order to maintain your own ranking, advantage, privilege, or to elevate yourself above others or to keep others beneath you.”

Reading “Caste: The Origins of Our Discontents” is akin to the experience of gaining relief after struggling for years with a chronic malady that has a fluctuating course: Under the surface is low-grade pain that is compartmentalized and often met with denial or gaslighting when symptoms and systems are reported to members of the dominant caste. Yet, when there are acute flare-ups and increasingly frequent deadly encounters, the defenses of denial are painfully revealed; structures are broken and sometimes burned down. This has been the clinical course of racism, particularly in the United States. In that vein, an early reaction while reading “Caste” might be comparable to hearing an interpretation that educates, clarifies, resonates, and lands perfectly on the right diagnosis at the right moment.
 

Approach proves clarifying

In conceptualizing the malady as one of caste, Ms. Wilkerson achieves several things simultaneously – she names the malady, thus providing a lexicon, describes its symptoms, and most importantly, in our opinion, shares some of the compelling data from her field studies. By focusing on India, Nazi Germany, and the United States, she describes how easily one system influences another in the global effort to maintain power among the privileged.

This is not a new way of conceptualizing racial hierarchy; however, what is truly persuasive is Ms. Wilkerson’s ability to weave her rigorous research, sociopolitical analysis, and cogent psychological insights and interpretations to explain the 400-year trajectory of racialized caste in the United States. She achieves this exigent task with beautiful prose that motivates the reader to return time and time again to learn gut-wrenching painful historical details. She summarizes truths that have been unearthed (again) about Germany, India, and, in particular, the United States during her research and travels around the world. In doing so, she provides vivid examples of racism layered on caste. Consider the following:

“The Nazis were impressed by the American custom of lynching its subordinate caste of African-Americans, having become aware of the ritual torture and mutilations that typically accompanied them. Hitler especially marveled at the American ‘knack for maintaining an air of robust innocence in the wake of mass death.’ ” Ms. Wilkerson informs us that Hitler sent emissaries to study America’s Jim Crow system and then imported some features to orchestrate the Holocaust in Nazi Germany.

Her most vivid example of internalized casteism is the experience of a Dalit scholar who still experiences anxiety and a corresponding sense of inadequacy in the presence of someone who is considered to be from a higher caste.

A painful account of interpersonal racism is captured as Ms. Wilkerson recounts her experience after a routine business flight from Chicago to Detroit. She details her difficulty leaving a rental car parking lot because she had become so disoriented after being profiled and accosted by Drug Enforcement Administration agents who had intercepted her in the airport terminal and followed her onto the airport shuttle bus as she attempted to reach her destination. She provides a description of “getting turned around in a parking lot that I had been to dozens of times, going in circles, not able to get out, not registering the signs to the exit, not seeing how to get to Interstate 94, when I knew full well how to get to I-94 after all the times I’d driven it. ... This was the thievery of caste, stealing the time and psychic resources of the marginalized, draining energy in an already uphill competition. They were not, like me, frozen and disoriented, trying to make sense of a public violation that seemed all the more menacing now that I could see it in full. The quiet mundanity of that terror has never left me, the scars outliving the cut.”

This account is consistent with the dissociative, disorienting dynamics of race-based trauma. Her experience is not uncommon and helps to explain the activism of those in the subordinate caste who have attained some measure of wealth, power, and influence, and are motivated to expend their resources (energy, time, fame, and/or wealth) to raise awareness about social and political injustices by calling out structural racism in medicine, protesting police use of force by taking a knee, boycotting sporting events, and even demanding that football stadiums be used as polling sites. At the end of the day, all of us who have “made it” know that when we leave our homes, our relegation to the subordinate caste determines how we are perceived and what landmines we must navigate to make it through the day and that determine whether we will make it home.

This tour de force work of art has the potential to be a game changer in the way that we think about racial polarization in the United States. It is hoped that this new language opens up a space that allows each of us to explore this hegemony while identifying our placement and actions we take to maintain it, for each of us undeniably has a position in this caste system.

Having this new lexicon summons to mind the reactions of patients who gain immediate relief from having their illnesses named. In the case of the U.S. malady that has gripped us all, Ms. Wilkerson reiterates the importance of naming the condition. She writes:

“Because, to truly understand America, we must open our eyes to the hidden work of a caste system that has gone unnamed but prevails among us to our collective detriment, to see that we have more in common with each other and with cultures that we might otherwise dismiss, and to summon the courage to consider that therein may lie the answers.”

The naming allows both doctor and patient to have greater insight, understanding its origins and course, as well as having hope that there is a remedy. Naming facilitates the space for a shift in thinking and implementation of treatment protocols, such as Nazi Germany’s “zero tolerance policy” of swastikas in comparison to the ongoing U.S. controversy about the display of Confederate symbols. At this point in history, we welcome a diagnosis that has the potential to shift us from these poles of dominant and subordinate, black and white, good and bad, toward integration and wholeness of the individual psyche and collective global community. This is similar to what Melanie Klein calls the depressive position. Ms. Wilkerson suggests, in relinquishing these polar splits, we increase our capacity to shift to a space where our psychic integration occurs and our inextricable interdependence and responsibility for one another are honored.
 

Dr. Dunlap is a psychiatrist and psychoanalyst, and clinical professor of psychiatry and behavioral sciences at George Washington University. She is interested in the management of “difference” – race, gender, ethnicity, and intersectionality – in dyadic relationships and group dynamics; and the impact of racism on interpersonal relationships in institutional structures. Dr. Dunlap practices in Washington and has no disclosures. Dr. Dennis is a clinical psychologist and psychoanalyst. Her interests are in gender and ethnic diversity, health equity, and supervision and training. Dr. Dennis practices in Washington and has no disclosures.

Suicide rates in young people aged 10-24 years increased significantly in 42 states from 2007-2009 to 2016-2018, according to a recent analysis from the National Center for Health Statistics.

Nationally, the suicide rate jumped 47%, based on the averages for the two 3-year periods, rising from 7.0 per 100,000 persons aged 10-24 years to 10.3 per 100,000. For all ages, the corresponding increase was 47%, Sally C. Curtin, MA, of the NCHS, said in a National Vital Statistics Report.

There was no state with a decrease in suicide rates for adolescents and young adults, as the other eight all had nonsignificant increases, the smallest being 14% in South Dakota. Three-year averages were used to increase statistical power for states with relatively small numbers of deaths but were still not enough to show significance for some large increases, such as the 48% rise in Delaware, Ms. Curtin noted.

In 2016-2018, Alaska’s suicide rate of 31.8 per 100,000 persons aged 10-24 years was the highest in the country, followed by South Dakota (23.6), Montana (23.2), and Wyoming (20.5). New Jersey had the lowest rate at 5.7 per 100,000, with New York and Rhode Island both slightly higher at 5.9 and Connecticut at 6.3, based on data from the National Vital Statistics System.

Even the low numbers, however, hide some large changes, as New Jersey (up by 39%) and New York (up by 44%) were among the 42 states with statistically significant increases, which ranged from 21.7% in Maryland to 110% in New Hampshire, Ms. Curtin said in the report. The increases seen in this analysis contrast with data from the preceding time period, as “the suicide rate among persons aged 10-24 was statistically stable from 2000 to 2007.”

[email protected]

SOURCE: Curtin SC. National Vital Statistics Reports. 2020;69(11)1-9.

Suicide rates in young people aged 10-24 years increased significantly in 42 states from 2007-2009 to 2016-2018, according to a recent analysis from the National Center for Health Statistics.

Nationally, the suicide rate jumped 47%, based on the averages for the two 3-year periods, rising from 7.0 per 100,000 persons aged 10-24 years to 10.3 per 100,000. For all ages, the corresponding increase was 47%, Sally C. Curtin, MA, of the NCHS, said in a National Vital Statistics Report.

There was no state with a decrease in suicide rates for adolescents and young adults, as the other eight all had nonsignificant increases, the smallest being 14% in South Dakota. Three-year averages were used to increase statistical power for states with relatively small numbers of deaths but were still not enough to show significance for some large increases, such as the 48% rise in Delaware, Ms. Curtin noted.

In 2016-2018, Alaska’s suicide rate of 31.8 per 100,000 persons aged 10-24 years was the highest in the country, followed by South Dakota (23.6), Montana (23.2), and Wyoming (20.5). New Jersey had the lowest rate at 5.7 per 100,000, with New York and Rhode Island both slightly higher at 5.9 and Connecticut at 6.3, based on data from the National Vital Statistics System.

Even the low numbers, however, hide some large changes, as New Jersey (up by 39%) and New York (up by 44%) were among the 42 states with statistically significant increases, which ranged from 21.7% in Maryland to 110% in New Hampshire, Ms. Curtin said in the report. The increases seen in this analysis contrast with data from the preceding time period, as “the suicide rate among persons aged 10-24 was statistically stable from 2000 to 2007.”

[email protected]

SOURCE: Curtin SC. National Vital Statistics Reports. 2020;69(11)1-9.

Suicide rates in young people aged 10-24 years increased significantly in 42 states from 2007-2009 to 2016-2018, according to a recent analysis from the National Center for Health Statistics.

Nationally, the suicide rate jumped 47%, based on the averages for the two 3-year periods, rising from 7.0 per 100,000 persons aged 10-24 years to 10.3 per 100,000. For all ages, the corresponding increase was 47%, Sally C. Curtin, MA, of the NCHS, said in a National Vital Statistics Report.

There was no state with a decrease in suicide rates for adolescents and young adults, as the other eight all had nonsignificant increases, the smallest being 14% in South Dakota. Three-year averages were used to increase statistical power for states with relatively small numbers of deaths but were still not enough to show significance for some large increases, such as the 48% rise in Delaware, Ms. Curtin noted.

In 2016-2018, Alaska’s suicide rate of 31.8 per 100,000 persons aged 10-24 years was the highest in the country, followed by South Dakota (23.6), Montana (23.2), and Wyoming (20.5). New Jersey had the lowest rate at 5.7 per 100,000, with New York and Rhode Island both slightly higher at 5.9 and Connecticut at 6.3, based on data from the National Vital Statistics System.

Even the low numbers, however, hide some large changes, as New Jersey (up by 39%) and New York (up by 44%) were among the 42 states with statistically significant increases, which ranged from 21.7% in Maryland to 110% in New Hampshire, Ms. Curtin said in the report. The increases seen in this analysis contrast with data from the preceding time period, as “the suicide rate among persons aged 10-24 was statistically stable from 2000 to 2007.”

[email protected]

SOURCE: Curtin SC. National Vital Statistics Reports. 2020;69(11)1-9.

States have begun preparing to distribute a COVID-19 vaccine if one is approved, a CDC official said today.

The CDC released guidance for states on Sept. 16 titled COVID-19 Vaccination Program Interim Playbook for Jurisdiction Operations. The document discusses vaccine ordering, storage, and handling and says that states should submit their plans for vaccine distribution to the agency by Oct. 16.

“Every jurisdiction is heavily involved right now in their plan development,” CDC official Janell Routh, MD, told the Advisory Committee on Immunization Practices during its Sept. 22 meeting. “It was really impressive to me that, even though the playbook only went out last week, states and jurisdictions have been thinking about this for quite some time.”

However, one committee member suggested that setting a deadline before more safety, efficacy, and storage information is known may be premature.

“I cannot imagine that we will actually know the final storage requirements for this vaccine by Oct. 16, which makes me a little concerned about finalizing state plans,” said Helen “Keipp” Talbot, MD, MPH, associate professor of medicine at Vanderbilt University Medical Center in Nashville, Tenn. “We also don’t know the best populations yet when it comes to efficacy and safety.”

Dr. Routh said the CDC is asking states to plan on the basis of assumptions. “We know those plans will constantly be improving, changing, as we learn more information,” Dr. Routh said. States agreed to return a plan 30 days after the playbook was released, which is how the Oct. 16 deadline was established, she said.

States are encouraged to think broadly. Plans may include contingencies for a product that requires ultracold storage or for distributing more than one vaccine product, Dr. Routh said.

“One goal is to be ready on the first day that we can actually distribute vaccine,” Nancy Messonnier, MD, director of the National Center for Immunization and Respiratory Diseases, said during the meeting. “Our colleagues in Operation Warp Speed say that they expect there will be vaccine as early as November, and therefore we need to be ready so there is no delay in distributing that vaccine. And that phase, that early phase, is really close upon us.”

Many states have already developed plans, and the CDC is providing technical assistance as needed to monitor the plans regularly, Dr. Routh said.
 

Key issues identified

From holding pilot meetings with five jurisdictions, officials learned that public confidence in the vaccine is among states’ greatest concerns, Dr. Routh said. In addition, distribution is resource intensive, and social distancing adds logistical complexity.

Specific guidance on whom to vaccinate in the early stages will smooth the process, officials suggested during the pilot meetings. For the first several weeks, vaccine doses may be limited to priority populations, such as health care workers.

“This interim playbook is a living document,” Dr. Routh emphasized. “We definitely plan to update the content regularly as we learn more information about what vaccines and when they will be released.”

During the early stages of COVID-19 vaccination, officials plan to implement an enhanced monitoring program in which vaccine recipients would complete surveys about adverse events, in addition to the traditional vaccine safety monitoring programs that already exist, officials said.
 

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

States have begun preparing to distribute a COVID-19 vaccine if one is approved, a CDC official said today.

The CDC released guidance for states on Sept. 16 titled COVID-19 Vaccination Program Interim Playbook for Jurisdiction Operations. The document discusses vaccine ordering, storage, and handling and says that states should submit their plans for vaccine distribution to the agency by Oct. 16.

“Every jurisdiction is heavily involved right now in their plan development,” CDC official Janell Routh, MD, told the Advisory Committee on Immunization Practices during its Sept. 22 meeting. “It was really impressive to me that, even though the playbook only went out last week, states and jurisdictions have been thinking about this for quite some time.”

However, one committee member suggested that setting a deadline before more safety, efficacy, and storage information is known may be premature.

“I cannot imagine that we will actually know the final storage requirements for this vaccine by Oct. 16, which makes me a little concerned about finalizing state plans,” said Helen “Keipp” Talbot, MD, MPH, associate professor of medicine at Vanderbilt University Medical Center in Nashville, Tenn. “We also don’t know the best populations yet when it comes to efficacy and safety.”

Dr. Routh said the CDC is asking states to plan on the basis of assumptions. “We know those plans will constantly be improving, changing, as we learn more information,” Dr. Routh said. States agreed to return a plan 30 days after the playbook was released, which is how the Oct. 16 deadline was established, she said.

States are encouraged to think broadly. Plans may include contingencies for a product that requires ultracold storage or for distributing more than one vaccine product, Dr. Routh said.

“One goal is to be ready on the first day that we can actually distribute vaccine,” Nancy Messonnier, MD, director of the National Center for Immunization and Respiratory Diseases, said during the meeting. “Our colleagues in Operation Warp Speed say that they expect there will be vaccine as early as November, and therefore we need to be ready so there is no delay in distributing that vaccine. And that phase, that early phase, is really close upon us.”

Many states have already developed plans, and the CDC is providing technical assistance as needed to monitor the plans regularly, Dr. Routh said.
 

Key issues identified

From holding pilot meetings with five jurisdictions, officials learned that public confidence in the vaccine is among states’ greatest concerns, Dr. Routh said. In addition, distribution is resource intensive, and social distancing adds logistical complexity.

Specific guidance on whom to vaccinate in the early stages will smooth the process, officials suggested during the pilot meetings. For the first several weeks, vaccine doses may be limited to priority populations, such as health care workers.

“This interim playbook is a living document,” Dr. Routh emphasized. “We definitely plan to update the content regularly as we learn more information about what vaccines and when they will be released.”

During the early stages of COVID-19 vaccination, officials plan to implement an enhanced monitoring program in which vaccine recipients would complete surveys about adverse events, in addition to the traditional vaccine safety monitoring programs that already exist, officials said.
 

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

States have begun preparing to distribute a COVID-19 vaccine if one is approved, a CDC official said today.

The CDC released guidance for states on Sept. 16 titled COVID-19 Vaccination Program Interim Playbook for Jurisdiction Operations. The document discusses vaccine ordering, storage, and handling and says that states should submit their plans for vaccine distribution to the agency by Oct. 16.

“Every jurisdiction is heavily involved right now in their plan development,” CDC official Janell Routh, MD, told the Advisory Committee on Immunization Practices during its Sept. 22 meeting. “It was really impressive to me that, even though the playbook only went out last week, states and jurisdictions have been thinking about this for quite some time.”

However, one committee member suggested that setting a deadline before more safety, efficacy, and storage information is known may be premature.

“I cannot imagine that we will actually know the final storage requirements for this vaccine by Oct. 16, which makes me a little concerned about finalizing state plans,” said Helen “Keipp” Talbot, MD, MPH, associate professor of medicine at Vanderbilt University Medical Center in Nashville, Tenn. “We also don’t know the best populations yet when it comes to efficacy and safety.”

Dr. Routh said the CDC is asking states to plan on the basis of assumptions. “We know those plans will constantly be improving, changing, as we learn more information,” Dr. Routh said. States agreed to return a plan 30 days after the playbook was released, which is how the Oct. 16 deadline was established, she said.

States are encouraged to think broadly. Plans may include contingencies for a product that requires ultracold storage or for distributing more than one vaccine product, Dr. Routh said.

“One goal is to be ready on the first day that we can actually distribute vaccine,” Nancy Messonnier, MD, director of the National Center for Immunization and Respiratory Diseases, said during the meeting. “Our colleagues in Operation Warp Speed say that they expect there will be vaccine as early as November, and therefore we need to be ready so there is no delay in distributing that vaccine. And that phase, that early phase, is really close upon us.”

Many states have already developed plans, and the CDC is providing technical assistance as needed to monitor the plans regularly, Dr. Routh said.
 

Key issues identified

From holding pilot meetings with five jurisdictions, officials learned that public confidence in the vaccine is among states’ greatest concerns, Dr. Routh said. In addition, distribution is resource intensive, and social distancing adds logistical complexity.

Specific guidance on whom to vaccinate in the early stages will smooth the process, officials suggested during the pilot meetings. For the first several weeks, vaccine doses may be limited to priority populations, such as health care workers.

“This interim playbook is a living document,” Dr. Routh emphasized. “We definitely plan to update the content regularly as we learn more information about what vaccines and when they will be released.”

During the early stages of COVID-19 vaccination, officials plan to implement an enhanced monitoring program in which vaccine recipients would complete surveys about adverse events, in addition to the traditional vaccine safety monitoring programs that already exist, officials said.
 

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

Current American and European guidelines recommending long-term beta-blocker therapy following an acute MI appear to be obsolete in the modern reperfusion era, suggests an analysis of Danish registry data.

Those guidelines are based on old randomized trials of beta-blocker therapy conducted prior to introduction of routine percutaneous coronary intervention and modern multidrug optimal medical therapy for acute MI. There have been no prospective controlled studies in the reperfusion era. And a new Danish national observational study strongly suggests it’s time to reexamine the beta-blocker recommendation, Anders Holt, MD, said at the virtual annual congress of the European Society of Cardiology.

“Stable, optimally treated MI patients do not seem to benefit from beta-blocker treatment exceeding 3 months post hospitalization – bearing in mind this doesn’t apply to patients with other indications for beta-blockers, like heart failure or atrial fibrillation,” said Dr. Holt of Copenhagen University Hospital.

His analysis of Danish national registry data on more than 30,000 patients hospitalized for acute MI during 2003-2018 earned him the annual ESC Young Investigator Award in Population Science.

Frontline Medical News

“This was a crisp and clear presentation of a very creative use of observational epidemiology to try to understand the length of therapy that may or may not be appropriate,” commented award session cochair Paul M. Ridker, MD, director of the Center for Cardiovascular Disease Prevention at Brigham and Women’s Hospital and professor of medicine at Harvard Medical School, both in Boston.

Dr. Holt reported on 30,177 patients optimally treated for a first MI in Danish hospitals during 2003-2018, none of whom had a prior indication or contraindication for beta-blocker therapy. “Optimally treated” meant they underwent percutaneous coronary revascularization and were discharged on a statin and aspirin. As a study requirement, all had to be stable 90 days post hospitalization, at which point 24,770 of the patients were on long-term beta-blocker therapy, and 5,407 (18%) were not. The two groups were comparable in terms of age, sex, comorbidities, and baseline medications. All patients were followed through the registries for a maximum of 3 years, the duration of beta-blocker therapy post MI recommended in American Heart Association/American College of Cardiology guidelines. (The Danish Society of Cardiology recommends 2 years.)

At 3 years post MI, there was no between-group difference in a composite outcome comprising cardiovascular death, recurrent MI, heart failure, stroke, angina, or a cardiac procedure, with a rate of 22.9% in the beta-blocker group and 21.6% in patients not on long-term beta-blocker therapy. The rate of recurrent MI was identical at 6.7% in both groups. Cardiovascular death occurred during 3 years of follow-up in 1.4% of patients on beta-blocker therapy and 1.7% who weren’t, a nonsignificant difference.

“We saw no evidence of any cardioprotective effect, but no increased risk of adverse events resulting in hospitalization, either,” Dr. Holt observed. “I would like to acknowledge that no evidence of effect does not necessarily equal evidence of no effect, but even if there was an effect we can with fair certainty say that it’s probably quite minimal.”

He noted that the Danish registry data indicates that each year since 2012 has shown a growing trend for Danish patients to dispense with long-term beta-blocker therapy after an acute MI.

“This might indicate we are nudging toward a change in practice, where more physicians are thinking that long-term beta-blocker therapy might not be indicated for all MI patients in the reperfusion era,” according to Dr. Holt.

Asked by the four-judge award panel about the possibility of unmeasured confounding in this observational study, Dr Holt responded: “I would be very cautious about asking patients to stop beta-blocker therapy after 3 months just based on this observational data. We can’t speak to causality in an observational study.” But he added that “well-designed observational studies provide valuable data regarding this topic and should not be ignored. They should possibly influence the guidelines and the designs for upcoming randomized trials.”

He conducted several supplementary analyses designed to address the possibility of unevenly distributed unmeasured confounding in the registry study. These analyses proved reassuring. A positive exposure control analysis compared 3-year outcomes in patients who remained on long-term statin therapy and those who didn’t. As expected, outcomes were significantly better in those who did: a 3-year composite outcome rate of 22.1%, compared with 32.1% in patients not on a statin; a cardiovascular death rate of 1.3% with and 2.1% without statin therapy; a recurrent MI rate of 6.6%, compared with 10.1% without a statin; and a 2.8% all-cause mortality with and 5.4% without statin therapy.

In contrast, all-cause mortality was unaffected by whether or not patients were on long-term beta-blocker therapy. And in a negative exposure outcome analysis, no association was found between beta-blocker therapy and the risk of hospitalization for pneumonia, as to be expected if the beta-blocker and no-beta-blocker groups were comparable in key respects.

Dr. Holt reported having no financial conflicts regarding his study.

[email protected]

Current American and European guidelines recommending long-term beta-blocker therapy following an acute MI appear to be obsolete in the modern reperfusion era, suggests an analysis of Danish registry data.

Those guidelines are based on old randomized trials of beta-blocker therapy conducted prior to introduction of routine percutaneous coronary intervention and modern multidrug optimal medical therapy for acute MI. There have been no prospective controlled studies in the reperfusion era. And a new Danish national observational study strongly suggests it’s time to reexamine the beta-blocker recommendation, Anders Holt, MD, said at the virtual annual congress of the European Society of Cardiology.

“Stable, optimally treated MI patients do not seem to benefit from beta-blocker treatment exceeding 3 months post hospitalization – bearing in mind this doesn’t apply to patients with other indications for beta-blockers, like heart failure or atrial fibrillation,” said Dr. Holt of Copenhagen University Hospital.

His analysis of Danish national registry data on more than 30,000 patients hospitalized for acute MI during 2003-2018 earned him the annual ESC Young Investigator Award in Population Science.

Frontline Medical News

“This was a crisp and clear presentation of a very creative use of observational epidemiology to try to understand the length of therapy that may or may not be appropriate,” commented award session cochair Paul M. Ridker, MD, director of the Center for Cardiovascular Disease Prevention at Brigham and Women’s Hospital and professor of medicine at Harvard Medical School, both in Boston.

Dr. Holt reported on 30,177 patients optimally treated for a first MI in Danish hospitals during 2003-2018, none of whom had a prior indication or contraindication for beta-blocker therapy. “Optimally treated” meant they underwent percutaneous coronary revascularization and were discharged on a statin and aspirin. As a study requirement, all had to be stable 90 days post hospitalization, at which point 24,770 of the patients were on long-term beta-blocker therapy, and 5,407 (18%) were not. The two groups were comparable in terms of age, sex, comorbidities, and baseline medications. All patients were followed through the registries for a maximum of 3 years, the duration of beta-blocker therapy post MI recommended in American Heart Association/American College of Cardiology guidelines. (The Danish Society of Cardiology recommends 2 years.)

At 3 years post MI, there was no between-group difference in a composite outcome comprising cardiovascular death, recurrent MI, heart failure, stroke, angina, or a cardiac procedure, with a rate of 22.9% in the beta-blocker group and 21.6% in patients not on long-term beta-blocker therapy. The rate of recurrent MI was identical at 6.7% in both groups. Cardiovascular death occurred during 3 years of follow-up in 1.4% of patients on beta-blocker therapy and 1.7% who weren’t, a nonsignificant difference.

“We saw no evidence of any cardioprotective effect, but no increased risk of adverse events resulting in hospitalization, either,” Dr. Holt observed. “I would like to acknowledge that no evidence of effect does not necessarily equal evidence of no effect, but even if there was an effect we can with fair certainty say that it’s probably quite minimal.”

He noted that the Danish registry data indicates that each year since 2012 has shown a growing trend for Danish patients to dispense with long-term beta-blocker therapy after an acute MI.

“This might indicate we are nudging toward a change in practice, where more physicians are thinking that long-term beta-blocker therapy might not be indicated for all MI patients in the reperfusion era,” according to Dr. Holt.

Asked by the four-judge award panel about the possibility of unmeasured confounding in this observational study, Dr Holt responded: “I would be very cautious about asking patients to stop beta-blocker therapy after 3 months just based on this observational data. We can’t speak to causality in an observational study.” But he added that “well-designed observational studies provide valuable data regarding this topic and should not be ignored. They should possibly influence the guidelines and the designs for upcoming randomized trials.”

He conducted several supplementary analyses designed to address the possibility of unevenly distributed unmeasured confounding in the registry study. These analyses proved reassuring. A positive exposure control analysis compared 3-year outcomes in patients who remained on long-term statin therapy and those who didn’t. As expected, outcomes were significantly better in those who did: a 3-year composite outcome rate of 22.1%, compared with 32.1% in patients not on a statin; a cardiovascular death rate of 1.3% with and 2.1% without statin therapy; a recurrent MI rate of 6.6%, compared with 10.1% without a statin; and a 2.8% all-cause mortality with and 5.4% without statin therapy.

In contrast, all-cause mortality was unaffected by whether or not patients were on long-term beta-blocker therapy. And in a negative exposure outcome analysis, no association was found between beta-blocker therapy and the risk of hospitalization for pneumonia, as to be expected if the beta-blocker and no-beta-blocker groups were comparable in key respects.

Dr. Holt reported having no financial conflicts regarding his study.

[email protected]

Current American and European guidelines recommending long-term beta-blocker therapy following an acute MI appear to be obsolete in the modern reperfusion era, suggests an analysis of Danish registry data.

Those guidelines are based on old randomized trials of beta-blocker therapy conducted prior to introduction of routine percutaneous coronary intervention and modern multidrug optimal medical therapy for acute MI. There have been no prospective controlled studies in the reperfusion era. And a new Danish national observational study strongly suggests it’s time to reexamine the beta-blocker recommendation, Anders Holt, MD, said at the virtual annual congress of the European Society of Cardiology.

“Stable, optimally treated MI patients do not seem to benefit from beta-blocker treatment exceeding 3 months post hospitalization – bearing in mind this doesn’t apply to patients with other indications for beta-blockers, like heart failure or atrial fibrillation,” said Dr. Holt of Copenhagen University Hospital.

His analysis of Danish national registry data on more than 30,000 patients hospitalized for acute MI during 2003-2018 earned him the annual ESC Young Investigator Award in Population Science.

Frontline Medical News

“This was a crisp and clear presentation of a very creative use of observational epidemiology to try to understand the length of therapy that may or may not be appropriate,” commented award session cochair Paul M. Ridker, MD, director of the Center for Cardiovascular Disease Prevention at Brigham and Women’s Hospital and professor of medicine at Harvard Medical School, both in Boston.

Dr. Holt reported on 30,177 patients optimally treated for a first MI in Danish hospitals during 2003-2018, none of whom had a prior indication or contraindication for beta-blocker therapy. “Optimally treated” meant they underwent percutaneous coronary revascularization and were discharged on a statin and aspirin. As a study requirement, all had to be stable 90 days post hospitalization, at which point 24,770 of the patients were on long-term beta-blocker therapy, and 5,407 (18%) were not. The two groups were comparable in terms of age, sex, comorbidities, and baseline medications. All patients were followed through the registries for a maximum of 3 years, the duration of beta-blocker therapy post MI recommended in American Heart Association/American College of Cardiology guidelines. (The Danish Society of Cardiology recommends 2 years.)

At 3 years post MI, there was no between-group difference in a composite outcome comprising cardiovascular death, recurrent MI, heart failure, stroke, angina, or a cardiac procedure, with a rate of 22.9% in the beta-blocker group and 21.6% in patients not on long-term beta-blocker therapy. The rate of recurrent MI was identical at 6.7% in both groups. Cardiovascular death occurred during 3 years of follow-up in 1.4% of patients on beta-blocker therapy and 1.7% who weren’t, a nonsignificant difference.

“We saw no evidence of any cardioprotective effect, but no increased risk of adverse events resulting in hospitalization, either,” Dr. Holt observed. “I would like to acknowledge that no evidence of effect does not necessarily equal evidence of no effect, but even if there was an effect we can with fair certainty say that it’s probably quite minimal.”

He noted that the Danish registry data indicates that each year since 2012 has shown a growing trend for Danish patients to dispense with long-term beta-blocker therapy after an acute MI.

“This might indicate we are nudging toward a change in practice, where more physicians are thinking that long-term beta-blocker therapy might not be indicated for all MI patients in the reperfusion era,” according to Dr. Holt.

Asked by the four-judge award panel about the possibility of unmeasured confounding in this observational study, Dr Holt responded: “I would be very cautious about asking patients to stop beta-blocker therapy after 3 months just based on this observational data. We can’t speak to causality in an observational study.” But he added that “well-designed observational studies provide valuable data regarding this topic and should not be ignored. They should possibly influence the guidelines and the designs for upcoming randomized trials.”

He conducted several supplementary analyses designed to address the possibility of unevenly distributed unmeasured confounding in the registry study. These analyses proved reassuring. A positive exposure control analysis compared 3-year outcomes in patients who remained on long-term statin therapy and those who didn’t. As expected, outcomes were significantly better in those who did: a 3-year composite outcome rate of 22.1%, compared with 32.1% in patients not on a statin; a cardiovascular death rate of 1.3% with and 2.1% without statin therapy; a recurrent MI rate of 6.6%, compared with 10.1% without a statin; and a 2.8% all-cause mortality with and 5.4% without statin therapy.

In contrast, all-cause mortality was unaffected by whether or not patients were on long-term beta-blocker therapy. And in a negative exposure outcome analysis, no association was found between beta-blocker therapy and the risk of hospitalization for pneumonia, as to be expected if the beta-blocker and no-beta-blocker groups were comparable in key respects.

Dr. Holt reported having no financial conflicts regarding his study.

[email protected]

Prognoses for patients with AIDS-associated, non-Hodgkin lymphomas (AIDS-NHLs) have improved dramatically as HIV/AIDS has become easier to treat, and “we’re actually seeing patients with long-term remissions that are translating to cure,” a hematologist told colleagues at the virtual 2020 annual meeting of the Association of VA Hematology/Oncology (AVAHO).

“Even those with low CD4 counts initially have more chance of survival compared to the historic patients in the pre-HAART [highly active antiretroviral therapy] era,” explained Erin Reid, MD, MS, of the University of California at San Diego Moores Cancer Center. “They’re seeing complete-response rates and overall-survival rates that are nearly matching what we’re seeing in the non-HIV lymphoma cases. And aggressive infection prophylaxis has seemed to mitigate some of the infectious complications.”

Still, Reid said, a severe form of AIDS-NHL continues to have very poor outcomes, although specific regimens appear to be brightening the picture somewhat.

According to Dr. Reid, AIDS-NHLs are the most common malignancy in the HIV-positive population, and patients with these cancers are more likely to have aggressive lymphomas. These patients are also more likely to have lymphomas associated with Epstein-Barr virus—40 to 80%, depending on the subtype of lymphoma—and Kaposi sarcoma-associated herpesvirus (also known as human herpesvirus-8, or HHV8).

“These viruses are driving these cancers, and it begs the question of whether there’s something we can do to target these viruses within these cancer cells in a way that’s therapeutic,” she said.

Compared with the non-HIV population, patients with AIDS-NHL “are much more likely to present with advanced stage, extranodal disease and central nervous system involvement,” she said.

HAART Benefits

It’s become clear that HIV control via HAART has benefits in terms of higher tolerance of chemotherapy doses—“we’re able to use more full or traditional dose regimens”—and perhaps cancer suppression too, she said. A 2013 meta-analysis “favored concurrent therapy with chemotherapy [and HAART]. This has become our recommended standard of care for virtually all cases, except the very rare ones where you cannot find a regimen that is compatible from a PK [pharmacokinetics] standpoint.”

Reid also noted that the HAART era has changed the role of CD4 counts in AIDS-NHLs. “While CD4 count still has some predictive value, its impact on mortality appears attenuated,” she said.

EPOCH Treatment

With regard to treatment, she emphasized the importance of HAART: “We would recommend concurrent HAART whenever possible with chemotherapy, or start it immediately afterward.”

Aggressive infection prophylaxis also is recommended through granulocyte colony-stimulating factor and agents to target threats from pneumocystis jiroveci pneumonia, gram negative rods, and varicella-zoster virus. “I’ve moved away from fungal prophylaxis over the years, only dealing with it if there’s a known fungal infection,” she said.

As for treatment of AIDS-NHL, Reid Suggested that research supports the EPOCH regimen --etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin. However, “we still need strategies for refractory and relapsed disease,” she said.

Reid noted that she has started to see more plasmablastic cases, although her experience is anecdotal. Plasmablastic lymphoma is much more common in the HIV-positive setting, she said.

Lifespans are poor for these patients, with many failing to live for a year. But research hints that the prognosis in AIDS-NHL patients on HAART may actually be better than in the non-HIV population, she said.

A trial published in September 2020, in fact, reports that 87% of 15 patients with AIDS-associated plasmablastic lymphoma survived for at least one year on the EPOCH regimen. Overall, the study found that “people with a collection of HIV-associated lymphomas were doing well overall with the EPOCH backbone,” Reid explained.

Reid reported no relevant disclosures.

Prognoses for patients with AIDS-associated, non-Hodgkin lymphomas (AIDS-NHLs) have improved dramatically as HIV/AIDS has become easier to treat, and “we’re actually seeing patients with long-term remissions that are translating to cure,” a hematologist told colleagues at the virtual 2020 annual meeting of the Association of VA Hematology/Oncology (AVAHO).

“Even those with low CD4 counts initially have more chance of survival compared to the historic patients in the pre-HAART [highly active antiretroviral therapy] era,” explained Erin Reid, MD, MS, of the University of California at San Diego Moores Cancer Center. “They’re seeing complete-response rates and overall-survival rates that are nearly matching what we’re seeing in the non-HIV lymphoma cases. And aggressive infection prophylaxis has seemed to mitigate some of the infectious complications.”

Still, Reid said, a severe form of AIDS-NHL continues to have very poor outcomes, although specific regimens appear to be brightening the picture somewhat.

According to Dr. Reid, AIDS-NHLs are the most common malignancy in the HIV-positive population, and patients with these cancers are more likely to have aggressive lymphomas. These patients are also more likely to have lymphomas associated with Epstein-Barr virus—40 to 80%, depending on the subtype of lymphoma—and Kaposi sarcoma-associated herpesvirus (also known as human herpesvirus-8, or HHV8).

“These viruses are driving these cancers, and it begs the question of whether there’s something we can do to target these viruses within these cancer cells in a way that’s therapeutic,” she said.

Compared with the non-HIV population, patients with AIDS-NHL “are much more likely to present with advanced stage, extranodal disease and central nervous system involvement,” she said.

HAART Benefits

It’s become clear that HIV control via HAART has benefits in terms of higher tolerance of chemotherapy doses—“we’re able to use more full or traditional dose regimens”—and perhaps cancer suppression too, she said. A 2013 meta-analysis “favored concurrent therapy with chemotherapy [and HAART]. This has become our recommended standard of care for virtually all cases, except the very rare ones where you cannot find a regimen that is compatible from a PK [pharmacokinetics] standpoint.”

Reid also noted that the HAART era has changed the role of CD4 counts in AIDS-NHLs. “While CD4 count still has some predictive value, its impact on mortality appears attenuated,” she said.

EPOCH Treatment

With regard to treatment, she emphasized the importance of HAART: “We would recommend concurrent HAART whenever possible with chemotherapy, or start it immediately afterward.”

Aggressive infection prophylaxis also is recommended through granulocyte colony-stimulating factor and agents to target threats from pneumocystis jiroveci pneumonia, gram negative rods, and varicella-zoster virus. “I’ve moved away from fungal prophylaxis over the years, only dealing with it if there’s a known fungal infection,” she said.

As for treatment of AIDS-NHL, Reid Suggested that research supports the EPOCH regimen --etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin. However, “we still need strategies for refractory and relapsed disease,” she said.

Reid noted that she has started to see more plasmablastic cases, although her experience is anecdotal. Plasmablastic lymphoma is much more common in the HIV-positive setting, she said.

Lifespans are poor for these patients, with many failing to live for a year. But research hints that the prognosis in AIDS-NHL patients on HAART may actually be better than in the non-HIV population, she said.

A trial published in September 2020, in fact, reports that 87% of 15 patients with AIDS-associated plasmablastic lymphoma survived for at least one year on the EPOCH regimen. Overall, the study found that “people with a collection of HIV-associated lymphomas were doing well overall with the EPOCH backbone,” Reid explained.

Reid reported no relevant disclosures.

Prognoses for patients with AIDS-associated, non-Hodgkin lymphomas (AIDS-NHLs) have improved dramatically as HIV/AIDS has become easier to treat, and “we’re actually seeing patients with long-term remissions that are translating to cure,” a hematologist told colleagues at the virtual 2020 annual meeting of the Association of VA Hematology/Oncology (AVAHO).

“Even those with low CD4 counts initially have more chance of survival compared to the historic patients in the pre-HAART [highly active antiretroviral therapy] era,” explained Erin Reid, MD, MS, of the University of California at San Diego Moores Cancer Center. “They’re seeing complete-response rates and overall-survival rates that are nearly matching what we’re seeing in the non-HIV lymphoma cases. And aggressive infection prophylaxis has seemed to mitigate some of the infectious complications.”

Still, Reid said, a severe form of AIDS-NHL continues to have very poor outcomes, although specific regimens appear to be brightening the picture somewhat.

According to Dr. Reid, AIDS-NHLs are the most common malignancy in the HIV-positive population, and patients with these cancers are more likely to have aggressive lymphomas. These patients are also more likely to have lymphomas associated with Epstein-Barr virus—40 to 80%, depending on the subtype of lymphoma—and Kaposi sarcoma-associated herpesvirus (also known as human herpesvirus-8, or HHV8).

“These viruses are driving these cancers, and it begs the question of whether there’s something we can do to target these viruses within these cancer cells in a way that’s therapeutic,” she said.

Compared with the non-HIV population, patients with AIDS-NHL “are much more likely to present with advanced stage, extranodal disease and central nervous system involvement,” she said.

HAART Benefits

It’s become clear that HIV control via HAART has benefits in terms of higher tolerance of chemotherapy doses—“we’re able to use more full or traditional dose regimens”—and perhaps cancer suppression too, she said. A 2013 meta-analysis “favored concurrent therapy with chemotherapy [and HAART]. This has become our recommended standard of care for virtually all cases, except the very rare ones where you cannot find a regimen that is compatible from a PK [pharmacokinetics] standpoint.”

Reid also noted that the HAART era has changed the role of CD4 counts in AIDS-NHLs. “While CD4 count still has some predictive value, its impact on mortality appears attenuated,” she said.

EPOCH Treatment

With regard to treatment, she emphasized the importance of HAART: “We would recommend concurrent HAART whenever possible with chemotherapy, or start it immediately afterward.”

Aggressive infection prophylaxis also is recommended through granulocyte colony-stimulating factor and agents to target threats from pneumocystis jiroveci pneumonia, gram negative rods, and varicella-zoster virus. “I’ve moved away from fungal prophylaxis over the years, only dealing with it if there’s a known fungal infection,” she said.

As for treatment of AIDS-NHL, Reid Suggested that research supports the EPOCH regimen --etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin. However, “we still need strategies for refractory and relapsed disease,” she said.

Reid noted that she has started to see more plasmablastic cases, although her experience is anecdotal. Plasmablastic lymphoma is much more common in the HIV-positive setting, she said.

Lifespans are poor for these patients, with many failing to live for a year. But research hints that the prognosis in AIDS-NHL patients on HAART may actually be better than in the non-HIV population, she said.

A trial published in September 2020, in fact, reports that 87% of 15 patients with AIDS-associated plasmablastic lymphoma survived for at least one year on the EPOCH regimen. Overall, the study found that “people with a collection of HIV-associated lymphomas were doing well overall with the EPOCH backbone,” Reid explained.

Reid reported no relevant disclosures.

Although it may seem that veterans would have a very low risk of bleeding disorders since they were medically cleared for military service, a hematologist/oncologist cautioned that veterans might indeed suffer from both inherited and noninherited forms of these conditions. At the virtual 2020 annual meeting of the Association of VA Hematology/Oncology (AVAHO) Bethany Samuelson Bannow, MD, of Oregon Health & Science University’s Knight Cancer Institute urged colleagues to understand the diagnosis and treatment of bleeding disorders.

            “Most importantly, even though these are patients you probably don’t see on a regular basis, you are never alone,” since colleagues are available to help, she said. Samuelson Bannow treats patients at US Department of Veterans Affairs (VA) Portland Health Care System and used her presentation to focus on 4 types of bleeding disorders. A summary of her perspective and recommendations follows.

Acquired hemophilia: Watch for Infections

Acquired hemophilia affects only an estimated 1.3 to 1.5 in 1 million people, but VA physicians may see it more often since it affects an older population (median age is 78 years), Samuelson Bannow said. “I’ve seen about 4 cases in the last 2 years,” she said. “I’m not sure if we’re a magnet, but it does come up.”

The diagnosis is based on laboratory findings, and a lack of personal or family history of coagulopathy is key, she said. Twenty percent or more of patients older than 65 years die from the disorder, but bleeding usually isn’t the cause. Instead, patients tend to die from infections, she said.

Initial treatment must focus on stopping the bleeding, she said. The new drug porcine antihemophilic factor (recombinant)—Obizur—“is very helpful” and is Samuelson Bannow’s first choice, but it may not widely available at all VA medical centers. Recombinant FVIIa (NovoSeven) and activated prothrombin complex concentrate (Feiba) also are options.

            “The goal is to overpower the clotting cascade and get that burst of thrombin generation that you need to get the bleeding under control. Titrate to the amount of bleeding the patient is having, and make sure you’re doing local control as well,” Samuelson Bannow said. She added that the 2 agents may not work depending on the patient. Neither is preferred and both may be appropriate. “There’s no real reason to pick one over the other beyond convenience and availability.”

            There’s another “equally important component of management,” she said: Inhibitor eradication. “The only way to do this is with immune suppression. You’re going to have to suppress the immune system to get rid of the inhibitor. That’s why we see such high rates of death because we have to use heavy-hitter immunosuppressants.”

            Treatment options include steroids and cyclophosphamide (a common first-line option), rituximab, calcineurin inhibitors, and mycophenolate mofetil. “Just be aware that there is an increased risk of infection with these agents,” she said. “You want to see a decrease in the titer of your inhibitor. This can take 3 or more weeks, and it can take longer for it to disappear entirely. Look for normalized factor VIII level and absent inhibitor.”

            She added: “I tend to do a slow taper, one agent at a time, over the course of weeks. If you see a return of the inhibitor, you can ramp back up as needed. Continue to monitor for a year or more since patients are at high risk of recurrence.”

Acquired von Willebrand Syndrome: Fix the Associated Conditions

Acquired von Willebrand Syndrome is another rare bleeding disorder that may appear in veterans “since it’s associated with a lot of conditions that we see in the VA,” such as heart disorders, solid tumors, vascular malformations, and lymphoproliferative and myeloproliferative disorders, Samuelson Bannow said.

            As with acquired hemophilia, the key is to focus on controlling the bleeding, she said. Then, she advised, focus on the associated condition: “Correct the underlying disorder: Treat the malignancy, address the [cardiac] shear stress, correct hypothyroidism, correct the cardiac defects.”

Inherited Hemophilia: Don’t Rule It Out

It’s possible to “sneak through” military medical screening with undiagnosed inherited bleeding disorders, Dr. Samuelson Bannow said. That’s because service members may have never had an injury that triggered abnormal bleeding, she said. “You can see how someone could slip into the military with a [low clotting factor level]. The classic presentation is going to be joint bleeds and abnormalities. These can be traumatic and spontaneous without any kind of an injury,” she said.

            A general rule for these patients is to “replace what’s missing, and 100% is always normal.” The 100% refers to clotting factor level. She recommended reviewing 2013 guidelines for the treatment of the disorder.

Inherited von Willebrand Syndrome: Ask About Tonsillectomies

Inherited von Willebrand Syndrome is more common in women than it is in men. Bleeding “will primarily be mucocutaneous and trauma-induced,” said. Samuelson Bannow. She recommended asking patients if they have had a tonsillectomy and, if so, did they suffer from unusual bleeding. “If they did not have excessive bleeding, it’s a pretty good sign their hemostasis is good.”

            She recommends a nasal spray drug called desmopressin (DDAVP, Stimate) for management. “It’s critical to know that you must test for efficacy first,” she said. “One of the most common mistakes that people make is that they may give patients DDAVP before surgery without knowing if it works or not. It doesn’t work for every patient.” She typically avoids this drug in patients aged > 65 years, or even > 60 years, due to increased thrombosis risk.

            Recombinant von Willebrand factor (Vonvendi) is a “very helpful drug at patients at increased risk of thrombosis,” she said. However, she noted that the drug, at last check, is not on the VA’s formulary.

            At the end of her presentation, Samuelson Bannow urged colleagues to contact specialized Hemophilia Treatment Centers (HTCs) near them: “Follow this link, find an HTC [Hemophilia Treatment Center] near you, and create a partnership.”

Samuelson Bannow reported no relevant disclosures.

Although it may seem that veterans would have a very low risk of bleeding disorders since they were medically cleared for military service, a hematologist/oncologist cautioned that veterans might indeed suffer from both inherited and noninherited forms of these conditions. At the virtual 2020 annual meeting of the Association of VA Hematology/Oncology (AVAHO) Bethany Samuelson Bannow, MD, of Oregon Health & Science University’s Knight Cancer Institute urged colleagues to understand the diagnosis and treatment of bleeding disorders.

            “Most importantly, even though these are patients you probably don’t see on a regular basis, you are never alone,” since colleagues are available to help, she said. Samuelson Bannow treats patients at US Department of Veterans Affairs (VA) Portland Health Care System and used her presentation to focus on 4 types of bleeding disorders. A summary of her perspective and recommendations follows.

Acquired hemophilia: Watch for Infections

Acquired hemophilia affects only an estimated 1.3 to 1.5 in 1 million people, but VA physicians may see it more often since it affects an older population (median age is 78 years), Samuelson Bannow said. “I’ve seen about 4 cases in the last 2 years,” she said. “I’m not sure if we’re a magnet, but it does come up.”

The diagnosis is based on laboratory findings, and a lack of personal or family history of coagulopathy is key, she said. Twenty percent or more of patients older than 65 years die from the disorder, but bleeding usually isn’t the cause. Instead, patients tend to die from infections, she said.

Initial treatment must focus on stopping the bleeding, she said. The new drug porcine antihemophilic factor (recombinant)—Obizur—“is very helpful” and is Samuelson Bannow’s first choice, but it may not widely available at all VA medical centers. Recombinant FVIIa (NovoSeven) and activated prothrombin complex concentrate (Feiba) also are options.

            “The goal is to overpower the clotting cascade and get that burst of thrombin generation that you need to get the bleeding under control. Titrate to the amount of bleeding the patient is having, and make sure you’re doing local control as well,” Samuelson Bannow said. She added that the 2 agents may not work depending on the patient. Neither is preferred and both may be appropriate. “There’s no real reason to pick one over the other beyond convenience and availability.”

            There’s another “equally important component of management,” she said: Inhibitor eradication. “The only way to do this is with immune suppression. You’re going to have to suppress the immune system to get rid of the inhibitor. That’s why we see such high rates of death because we have to use heavy-hitter immunosuppressants.”

            Treatment options include steroids and cyclophosphamide (a common first-line option), rituximab, calcineurin inhibitors, and mycophenolate mofetil. “Just be aware that there is an increased risk of infection with these agents,” she said. “You want to see a decrease in the titer of your inhibitor. This can take 3 or more weeks, and it can take longer for it to disappear entirely. Look for normalized factor VIII level and absent inhibitor.”

            She added: “I tend to do a slow taper, one agent at a time, over the course of weeks. If you see a return of the inhibitor, you can ramp back up as needed. Continue to monitor for a year or more since patients are at high risk of recurrence.”