Hematology News

Adults with sickle cell disease who experienced a vaso-occlusive crisis had substantially better outcomes when they were treated at specialty infusion centers than those treated in emergency departments (EDs), a prospective observational study shows.

At infusion centers, patients received pain medication an average of 70 minutes faster compared with patients treated in EDs (62 vs. 132 minutes), according to a study published online in the Annals of Internal Medicine. In addition, patients at infusion centers were 3.8 times more likely to have their pain reassessed within 30 minutes of the first dose. And they were 4 times more likely to be discharged home, the researchers found.

“It’s not that the emergency room doctors don’t want to do the right thing,” study author Sophie Lanzkron, MD, said in an interview. “They do, but they aren’t experts in sickle cell disease. They work in an emergency room, which is an incredibly busy, stressful place where they see trauma and heart attacks and strokes and all of these things that need emergency care. And so it just is not the right setting to treat people with sickle cell disease.”

To assess whether care at specialty infusion centers or EDs leads to better outcomes for patients with sickle cell disease with uncomplicated vaso-occlusive crises, Dr. Lanzkron, director of the Sickle Cell Center for Adults at the Johns Hopkins Hospital, Baltimore, and colleagues conducted the ESCAPED (Examining Sickle Cell Acute Pain in the Emergency vs. Day Hospital) study.

The trial included 483 adults with sickle cell disease who lived within 60 miles of an infusion center in four U.S. cities: Baltimore, Maryland; Cleveland, Ohio; Milwaukee, Wisconsin; and Baton Rouge, Louisiana. Investigators recruited patients between April 2015 and December 2016 and followed them for 18 months after enrollment.

The present analysis focused on data from 269 participants who had infusion center visits or ED visits that occurred during weekdays when infusion centers were open. Two sites had infusion centers solely for adults with sickle cell disease (Baltimore and Milwaukee), and two infusion centers shared infusion space with other hematology-oncology patients. All four sites were in hospitals that also had EDs. 

Although participants may have received comprehensive care at one of the sites with an infusion center, those who lived farther from an infusion center were likely to receive care for acute pain at an ED closer to home, the authors explain in the article.

The investigators used propensity score methodology to balance patient characteristics in the study groups.
 

Quick, effective pain reduction is beneficial

The results suggest that infusion centers “are more likely to provide guideline-based care than EDs,” and this care “can improve overall outcomes,” the authors write. 

Although the specialty infusion centers the researchers studied used various models, similar outcomes were seen at all of them.

The study did not include patients who had complications of sickle cell disease in addition to vaso-occlusive crisis, the researchers note. 

“[Because] the magnitude of the treatment effects estimated in our study is large and we have captured most of the important potential confounders, an unmeasured confounder that can nullify the treatment effect is unlikely to exist,” the authors write. 

“Sickle cell disease is a complicated condition that affects multiple organs. Patients who present with acute pain will have better outcomes being treated under providers who know and understand the disease,” commented Julie Kanter, MD, director of the adult sickle cell disease program and codirector of the Comprehensive Sickle Cell Center at the University of Alabama at Birmingham. “Specialized infusion centers offer the opportunity to both improve outcomes and decrease the cost of care. Most importantly, it is better for the individual with sickle cell disease,” she said.

Dr. Kanter wrote an accompanying editorial about the ESCAPED findings. The editorialist notes that “opioid medications are the only option to reduce the pain caused by microvascular injury” in patients with sickle cell crisis, although these treatments do not reduce the underlying damage and have substantial side effects and risks. Nevertheless, “quick and effective reduction of pain can allow patients to more easily move, stretch, and breathe ... important to increase oxygenation and restore blood flow, which will eventually abate the crisis,” Dr. Kanter wrote. 

The study shows that the infusion center treatment approach can benefit patients across different settings, commented John J. Strouse, MD, PhD, medical director of the adult sickle cell program at Duke University Sickle Cell Center, Durham, N.C., who was not involved in the study. 

“They show that they can definitely get closer to the recommendations of guidelines for acute pain management and sickle cell disease” in a setting that is focused on one problem, he said. “The other piece that is really important is that people are much more likely to go home if you follow the guideline.”
 

Infusion centers are scarce

“These systems need to be built,” Dr. Lanzkron said. “In most places, patients don’t have access to the infusion center model for their care. And in some places, it is not going to be practical.” Still, there may be ways to establish infusion locations, such as at oncology centers. And while there are challenges to delivering sickle cell disease care in EDs, “emergency rooms need to try to meet the needs of this patient population as best as they can,” Dr. Lanzkron said.

“Structural racism has played a role in the quality of care delivered” to patients with sickle cell disease, Dr. Lanzkron said. “The big message is [that] there is a better way to do this.” 

The study was funded by the Patient-Centered Outcomes Research Institute. Dr. Lanzkron’s disclosures included grants or contracts with government agencies and companies that are paid to her institution, as well as consulting fees from Bluebird Bio, Novo Nordisk, and Pfizer. Coauthors have disclosed working with sickle cell organizations and various medical companies. Dr. Kanter and Dr. Strouse have reported no relevant financial relationships.

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

Adults with sickle cell disease who experienced a vaso-occlusive crisis had substantially better outcomes when they were treated at specialty infusion centers than those treated in emergency departments (EDs), a prospective observational study shows.

At infusion centers, patients received pain medication an average of 70 minutes faster compared with patients treated in EDs (62 vs. 132 minutes), according to a study published online in the Annals of Internal Medicine. In addition, patients at infusion centers were 3.8 times more likely to have their pain reassessed within 30 minutes of the first dose. And they were 4 times more likely to be discharged home, the researchers found.

“It’s not that the emergency room doctors don’t want to do the right thing,” study author Sophie Lanzkron, MD, said in an interview. “They do, but they aren’t experts in sickle cell disease. They work in an emergency room, which is an incredibly busy, stressful place where they see trauma and heart attacks and strokes and all of these things that need emergency care. And so it just is not the right setting to treat people with sickle cell disease.”

To assess whether care at specialty infusion centers or EDs leads to better outcomes for patients with sickle cell disease with uncomplicated vaso-occlusive crises, Dr. Lanzkron, director of the Sickle Cell Center for Adults at the Johns Hopkins Hospital, Baltimore, and colleagues conducted the ESCAPED (Examining Sickle Cell Acute Pain in the Emergency vs. Day Hospital) study.

The trial included 483 adults with sickle cell disease who lived within 60 miles of an infusion center in four U.S. cities: Baltimore, Maryland; Cleveland, Ohio; Milwaukee, Wisconsin; and Baton Rouge, Louisiana. Investigators recruited patients between April 2015 and December 2016 and followed them for 18 months after enrollment.

The present analysis focused on data from 269 participants who had infusion center visits or ED visits that occurred during weekdays when infusion centers were open. Two sites had infusion centers solely for adults with sickle cell disease (Baltimore and Milwaukee), and two infusion centers shared infusion space with other hematology-oncology patients. All four sites were in hospitals that also had EDs. 

Although participants may have received comprehensive care at one of the sites with an infusion center, those who lived farther from an infusion center were likely to receive care for acute pain at an ED closer to home, the authors explain in the article.

The investigators used propensity score methodology to balance patient characteristics in the study groups.
 

Quick, effective pain reduction is beneficial

The results suggest that infusion centers “are more likely to provide guideline-based care than EDs,” and this care “can improve overall outcomes,” the authors write. 

Although the specialty infusion centers the researchers studied used various models, similar outcomes were seen at all of them.

The study did not include patients who had complications of sickle cell disease in addition to vaso-occlusive crisis, the researchers note. 

“[Because] the magnitude of the treatment effects estimated in our study is large and we have captured most of the important potential confounders, an unmeasured confounder that can nullify the treatment effect is unlikely to exist,” the authors write. 

“Sickle cell disease is a complicated condition that affects multiple organs. Patients who present with acute pain will have better outcomes being treated under providers who know and understand the disease,” commented Julie Kanter, MD, director of the adult sickle cell disease program and codirector of the Comprehensive Sickle Cell Center at the University of Alabama at Birmingham. “Specialized infusion centers offer the opportunity to both improve outcomes and decrease the cost of care. Most importantly, it is better for the individual with sickle cell disease,” she said.

Dr. Kanter wrote an accompanying editorial about the ESCAPED findings. The editorialist notes that “opioid medications are the only option to reduce the pain caused by microvascular injury” in patients with sickle cell crisis, although these treatments do not reduce the underlying damage and have substantial side effects and risks. Nevertheless, “quick and effective reduction of pain can allow patients to more easily move, stretch, and breathe ... important to increase oxygenation and restore blood flow, which will eventually abate the crisis,” Dr. Kanter wrote. 

The study shows that the infusion center treatment approach can benefit patients across different settings, commented John J. Strouse, MD, PhD, medical director of the adult sickle cell program at Duke University Sickle Cell Center, Durham, N.C., who was not involved in the study. 

“They show that they can definitely get closer to the recommendations of guidelines for acute pain management and sickle cell disease” in a setting that is focused on one problem, he said. “The other piece that is really important is that people are much more likely to go home if you follow the guideline.”
 

Infusion centers are scarce

“These systems need to be built,” Dr. Lanzkron said. “In most places, patients don’t have access to the infusion center model for their care. And in some places, it is not going to be practical.” Still, there may be ways to establish infusion locations, such as at oncology centers. And while there are challenges to delivering sickle cell disease care in EDs, “emergency rooms need to try to meet the needs of this patient population as best as they can,” Dr. Lanzkron said.

“Structural racism has played a role in the quality of care delivered” to patients with sickle cell disease, Dr. Lanzkron said. “The big message is [that] there is a better way to do this.” 

The study was funded by the Patient-Centered Outcomes Research Institute. Dr. Lanzkron’s disclosures included grants or contracts with government agencies and companies that are paid to her institution, as well as consulting fees from Bluebird Bio, Novo Nordisk, and Pfizer. Coauthors have disclosed working with sickle cell organizations and various medical companies. Dr. Kanter and Dr. Strouse have reported no relevant financial relationships.

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

Adults with sickle cell disease who experienced a vaso-occlusive crisis had substantially better outcomes when they were treated at specialty infusion centers than those treated in emergency departments (EDs), a prospective observational study shows.

At infusion centers, patients received pain medication an average of 70 minutes faster compared with patients treated in EDs (62 vs. 132 minutes), according to a study published online in the Annals of Internal Medicine. In addition, patients at infusion centers were 3.8 times more likely to have their pain reassessed within 30 minutes of the first dose. And they were 4 times more likely to be discharged home, the researchers found.

“It’s not that the emergency room doctors don’t want to do the right thing,” study author Sophie Lanzkron, MD, said in an interview. “They do, but they aren’t experts in sickle cell disease. They work in an emergency room, which is an incredibly busy, stressful place where they see trauma and heart attacks and strokes and all of these things that need emergency care. And so it just is not the right setting to treat people with sickle cell disease.”

To assess whether care at specialty infusion centers or EDs leads to better outcomes for patients with sickle cell disease with uncomplicated vaso-occlusive crises, Dr. Lanzkron, director of the Sickle Cell Center for Adults at the Johns Hopkins Hospital, Baltimore, and colleagues conducted the ESCAPED (Examining Sickle Cell Acute Pain in the Emergency vs. Day Hospital) study.

The trial included 483 adults with sickle cell disease who lived within 60 miles of an infusion center in four U.S. cities: Baltimore, Maryland; Cleveland, Ohio; Milwaukee, Wisconsin; and Baton Rouge, Louisiana. Investigators recruited patients between April 2015 and December 2016 and followed them for 18 months after enrollment.

The present analysis focused on data from 269 participants who had infusion center visits or ED visits that occurred during weekdays when infusion centers were open. Two sites had infusion centers solely for adults with sickle cell disease (Baltimore and Milwaukee), and two infusion centers shared infusion space with other hematology-oncology patients. All four sites were in hospitals that also had EDs. 

Although participants may have received comprehensive care at one of the sites with an infusion center, those who lived farther from an infusion center were likely to receive care for acute pain at an ED closer to home, the authors explain in the article.

The investigators used propensity score methodology to balance patient characteristics in the study groups.
 

Quick, effective pain reduction is beneficial

The results suggest that infusion centers “are more likely to provide guideline-based care than EDs,” and this care “can improve overall outcomes,” the authors write. 

Although the specialty infusion centers the researchers studied used various models, similar outcomes were seen at all of them.

The study did not include patients who had complications of sickle cell disease in addition to vaso-occlusive crisis, the researchers note. 

“[Because] the magnitude of the treatment effects estimated in our study is large and we have captured most of the important potential confounders, an unmeasured confounder that can nullify the treatment effect is unlikely to exist,” the authors write. 

“Sickle cell disease is a complicated condition that affects multiple organs. Patients who present with acute pain will have better outcomes being treated under providers who know and understand the disease,” commented Julie Kanter, MD, director of the adult sickle cell disease program and codirector of the Comprehensive Sickle Cell Center at the University of Alabama at Birmingham. “Specialized infusion centers offer the opportunity to both improve outcomes and decrease the cost of care. Most importantly, it is better for the individual with sickle cell disease,” she said.

Dr. Kanter wrote an accompanying editorial about the ESCAPED findings. The editorialist notes that “opioid medications are the only option to reduce the pain caused by microvascular injury” in patients with sickle cell crisis, although these treatments do not reduce the underlying damage and have substantial side effects and risks. Nevertheless, “quick and effective reduction of pain can allow patients to more easily move, stretch, and breathe ... important to increase oxygenation and restore blood flow, which will eventually abate the crisis,” Dr. Kanter wrote. 

The study shows that the infusion center treatment approach can benefit patients across different settings, commented John J. Strouse, MD, PhD, medical director of the adult sickle cell program at Duke University Sickle Cell Center, Durham, N.C., who was not involved in the study. 

“They show that they can definitely get closer to the recommendations of guidelines for acute pain management and sickle cell disease” in a setting that is focused on one problem, he said. “The other piece that is really important is that people are much more likely to go home if you follow the guideline.”
 

Infusion centers are scarce

“These systems need to be built,” Dr. Lanzkron said. “In most places, patients don’t have access to the infusion center model for their care. And in some places, it is not going to be practical.” Still, there may be ways to establish infusion locations, such as at oncology centers. And while there are challenges to delivering sickle cell disease care in EDs, “emergency rooms need to try to meet the needs of this patient population as best as they can,” Dr. Lanzkron said.

“Structural racism has played a role in the quality of care delivered” to patients with sickle cell disease, Dr. Lanzkron said. “The big message is [that] there is a better way to do this.” 

The study was funded by the Patient-Centered Outcomes Research Institute. Dr. Lanzkron’s disclosures included grants or contracts with government agencies and companies that are paid to her institution, as well as consulting fees from Bluebird Bio, Novo Nordisk, and Pfizer. Coauthors have disclosed working with sickle cell organizations and various medical companies. Dr. Kanter and Dr. Strouse have reported no relevant financial relationships.

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

The hashtag #BigHoopEnergy has sparked an online conversation about how women of color in the medical field are pressured to conform to traditional standards of professional appearance.

It started when a Latina doctor tweeted that she lost points on a practical exam in medical school because of her hoop earrings, with the evaluator writing “earrings, unprofessional.”

That led other female doctors to cite their own experiences, reported The Lily, a Washington Post publication aimed at millennial women. Many women posted photos of themselves wearing hoops, which have long been associated with Latina and African American women, the outlet said.

“There’s a big movement to police women of color and how they present themselves in medical spaces,” said Briana Christophers, an MD-PhD student at the Tri-Institutional MD-PhD Program in New York. “I think in part it’s a way of trying to make people who don’t usually fit the mold, fit the mold.”

Ms. Christophers, who identifies as Latina, said she was urged to wear a black or navy suit when interviewing for doctorate programs. She wore a black suit with a lavender blouse and received comments about that – some positive, some not, she said.

“Sometimes you don’t know how to interpret those sorts of comments,” Ms. Christophers said. “Do you remember because you like the shirt, or because you don’t think I should have done that?”

Doctors of color still stand out in American medicine. The Lily cited the Association of American Medical Colleges as saying that in 2018, Hispanics made up 5.8% of active American doctors and African Americans made up 5%.

Studies show that medical professionals of color often don’t receive the same respect as their White counterparts, with some people questioning whether they’re actually doctors.

“At work, wearing my white coat that has my name pretty big on it with a badge that says doctor on it, I still get asked if I’m the environmental services staff,” Alexandra Sims, MD, a pediatrician in Cincinnati, told The Lily. “I think it just demonstrates how deeply ingrained bias, racism, and sexism are in society and that we have a lot of work to do to disrupt that.”

Dr. Sims said the tweet about hoop earrings led her to wonder about daily decisions she makes about dress.

“Am I too much? Is this too much? Is this earring too big? Is this nail polish color too loud? And how will that be received at work?” she said, noting that she may opt not to wear hoops in certain situations, such as when she’s dealing with a grabby baby.

Monica Verduzco-Gutierrez, MD, professor and chair of the department of rehabilitation medicine at University of Texas Health, San Antonio, said doctors should be judged on the care they provide, not their appearance.

“Judging someone based on their earrings or their jumpsuit or whatever else that they’re noticing about the student is not an appropriate way to judge the student’s ability to take care of a patient,” Dr. Verduzco-Gutierrez said, noting that she was not speaking on behalf of the school.
 

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

The hashtag #BigHoopEnergy has sparked an online conversation about how women of color in the medical field are pressured to conform to traditional standards of professional appearance.

It started when a Latina doctor tweeted that she lost points on a practical exam in medical school because of her hoop earrings, with the evaluator writing “earrings, unprofessional.”

That led other female doctors to cite their own experiences, reported The Lily, a Washington Post publication aimed at millennial women. Many women posted photos of themselves wearing hoops, which have long been associated with Latina and African American women, the outlet said.

“There’s a big movement to police women of color and how they present themselves in medical spaces,” said Briana Christophers, an MD-PhD student at the Tri-Institutional MD-PhD Program in New York. “I think in part it’s a way of trying to make people who don’t usually fit the mold, fit the mold.”

Ms. Christophers, who identifies as Latina, said she was urged to wear a black or navy suit when interviewing for doctorate programs. She wore a black suit with a lavender blouse and received comments about that – some positive, some not, she said.

“Sometimes you don’t know how to interpret those sorts of comments,” Ms. Christophers said. “Do you remember because you like the shirt, or because you don’t think I should have done that?”

Doctors of color still stand out in American medicine. The Lily cited the Association of American Medical Colleges as saying that in 2018, Hispanics made up 5.8% of active American doctors and African Americans made up 5%.

Studies show that medical professionals of color often don’t receive the same respect as their White counterparts, with some people questioning whether they’re actually doctors.

“At work, wearing my white coat that has my name pretty big on it with a badge that says doctor on it, I still get asked if I’m the environmental services staff,” Alexandra Sims, MD, a pediatrician in Cincinnati, told The Lily. “I think it just demonstrates how deeply ingrained bias, racism, and sexism are in society and that we have a lot of work to do to disrupt that.”

Dr. Sims said the tweet about hoop earrings led her to wonder about daily decisions she makes about dress.

“Am I too much? Is this too much? Is this earring too big? Is this nail polish color too loud? And how will that be received at work?” she said, noting that she may opt not to wear hoops in certain situations, such as when she’s dealing with a grabby baby.

Monica Verduzco-Gutierrez, MD, professor and chair of the department of rehabilitation medicine at University of Texas Health, San Antonio, said doctors should be judged on the care they provide, not their appearance.

“Judging someone based on their earrings or their jumpsuit or whatever else that they’re noticing about the student is not an appropriate way to judge the student’s ability to take care of a patient,” Dr. Verduzco-Gutierrez said, noting that she was not speaking on behalf of the school.
 

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

The hashtag #BigHoopEnergy has sparked an online conversation about how women of color in the medical field are pressured to conform to traditional standards of professional appearance.

It started when a Latina doctor tweeted that she lost points on a practical exam in medical school because of her hoop earrings, with the evaluator writing “earrings, unprofessional.”

That led other female doctors to cite their own experiences, reported The Lily, a Washington Post publication aimed at millennial women. Many women posted photos of themselves wearing hoops, which have long been associated with Latina and African American women, the outlet said.

“There’s a big movement to police women of color and how they present themselves in medical spaces,” said Briana Christophers, an MD-PhD student at the Tri-Institutional MD-PhD Program in New York. “I think in part it’s a way of trying to make people who don’t usually fit the mold, fit the mold.”

Ms. Christophers, who identifies as Latina, said she was urged to wear a black or navy suit when interviewing for doctorate programs. She wore a black suit with a lavender blouse and received comments about that – some positive, some not, she said.

“Sometimes you don’t know how to interpret those sorts of comments,” Ms. Christophers said. “Do you remember because you like the shirt, or because you don’t think I should have done that?”

Doctors of color still stand out in American medicine. The Lily cited the Association of American Medical Colleges as saying that in 2018, Hispanics made up 5.8% of active American doctors and African Americans made up 5%.

Studies show that medical professionals of color often don’t receive the same respect as their White counterparts, with some people questioning whether they’re actually doctors.

“At work, wearing my white coat that has my name pretty big on it with a badge that says doctor on it, I still get asked if I’m the environmental services staff,” Alexandra Sims, MD, a pediatrician in Cincinnati, told The Lily. “I think it just demonstrates how deeply ingrained bias, racism, and sexism are in society and that we have a lot of work to do to disrupt that.”

Dr. Sims said the tweet about hoop earrings led her to wonder about daily decisions she makes about dress.

“Am I too much? Is this too much? Is this earring too big? Is this nail polish color too loud? And how will that be received at work?” she said, noting that she may opt not to wear hoops in certain situations, such as when she’s dealing with a grabby baby.

Monica Verduzco-Gutierrez, MD, professor and chair of the department of rehabilitation medicine at University of Texas Health, San Antonio, said doctors should be judged on the care they provide, not their appearance.

“Judging someone based on their earrings or their jumpsuit or whatever else that they’re noticing about the student is not an appropriate way to judge the student’s ability to take care of a patient,” Dr. Verduzco-Gutierrez said, noting that she was not speaking on behalf of the school.
 

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

Breast and cervical cancer screenings declined sharply in the early months of the COVID-19 pandemic, particularly among certain racial and ethnic minority groups and rural populations, notes the U.S. Centers for Disease Control and Prevention.

The new data come from the National Breast and Cervical Cancer Early Detection Program (NBCCEDP), a program that provides cancer screening services to women with low income and inadequate health insurance.

The data show that the total number of screenings funded by the NBCCEDP declined by 87% for breast cancer screening and by 84% for cervical cancer screening in April 2020 in comparison with the previous 5-year averages for that month.

The declines in breast cancer screening varied from 84% among Hispanic women to 98% among American Indian/Alaskan Native women. The declines in cervical cancer screening varied from 82% among Black women to 92% among Asian Pacific Islander women.

In April 2020, breast cancer screening declined by 86% in metro areas, 88% in urban areas, and 89% in rural areas in comparison with respective 5-year averages. For cervical cancer screenings, the corresponding declines were 85%, 77%, and 82%.

The findings are consistent with those from studies conducted in insured populations, note the authors, led by the Amy DeGroff, PhD, MPH, of the CDC’s National Center for Chronic Disease Prevention and Health Promotion.

“Prolonged delays in screening related to the COVID-19 pandemic may lead to delayed diagnoses, poor health consequences, and an increase in cancer disparities among women already experiencing health inequities,” the CDC states in a press release.

Women from racial and ethnic minority groups already face a disproportionate burden of cervical and breast cancers in the United States: Black women and Hispanic women have the highest rates of cervical cancer incidence (8.3 and 8.9 per 100,000 women, respectively, vs. 7.3 per 100,000 among White women) and the highest rates of cervical cancer deaths. Black women have the highest rate of breast cancer death (26.9 per 100,000 women, vs. 19.4 per 100,000 among White women), the study authors explain.

Although the volume of screening began to recover in May 2020 – test volumes for breast and cervical cancer were 39% and 40% below the 5-year average by June 2020 – breast cancer screening in rural areas remained 52% below the 5-year average, they report.

The findings were published online June 30 in Preventive Medicine.

“This study highlights a decline in cancer screening among women of racial and ethnic minority groups with low incomes when their access to medical services decreased at the beginning of the pandemic,” Dr. DeGroff comments in the CDC press release.

The findings “reinforce the need to safely maintain routine health care services during the pandemic, especially when the health care environment meets COVID-19 safety guidelines,” she adds.

The investigators used NBCCEDP administrative and program data reported to the CDC by awardees – organizations that receive funding to implement the NBCCEDP – to assess the impact of COVID-19 on the number of breast and cervical cancer screening tests administered through the program and the effects of COVID-19 on the availability of screening services and NBCCEDP awardees’ capacity to support partner clinics.

A total of 630,264 breast and 594,566 cervical cancer screening tests were conducted during the review period of January-June 2015-2020.

Despite COVID-related challenges, “a large number of awardees reported flexibility and creative efforts to reach women and support clinics’ resumption of clinical care, including screening, during the COVID-19 pandemic,” the authors write.

“[The] CDC encourages health care professionals to help minimize delays in testing by continuing routine cancer screening for women having symptoms or at high risk for breast or cervical cancer,” Dr. DeGroff commented. “The Early Detection Program can help women overcome barriers to health equity by educating them about the importance of routine screening, addressing their concerns about COVID-19 transmission, and helping them to safely access screening through interventions like patient navigation.”

Future studies will examine the effect of the pandemic on screening during the second half of 2020, when surges of COVID-19 and their timing varied geographically, they note.

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

Breast and cervical cancer screenings declined sharply in the early months of the COVID-19 pandemic, particularly among certain racial and ethnic minority groups and rural populations, notes the U.S. Centers for Disease Control and Prevention.

The new data come from the National Breast and Cervical Cancer Early Detection Program (NBCCEDP), a program that provides cancer screening services to women with low income and inadequate health insurance.

The data show that the total number of screenings funded by the NBCCEDP declined by 87% for breast cancer screening and by 84% for cervical cancer screening in April 2020 in comparison with the previous 5-year averages for that month.

The declines in breast cancer screening varied from 84% among Hispanic women to 98% among American Indian/Alaskan Native women. The declines in cervical cancer screening varied from 82% among Black women to 92% among Asian Pacific Islander women.

In April 2020, breast cancer screening declined by 86% in metro areas, 88% in urban areas, and 89% in rural areas in comparison with respective 5-year averages. For cervical cancer screenings, the corresponding declines were 85%, 77%, and 82%.

The findings are consistent with those from studies conducted in insured populations, note the authors, led by the Amy DeGroff, PhD, MPH, of the CDC’s National Center for Chronic Disease Prevention and Health Promotion.

“Prolonged delays in screening related to the COVID-19 pandemic may lead to delayed diagnoses, poor health consequences, and an increase in cancer disparities among women already experiencing health inequities,” the CDC states in a press release.

Women from racial and ethnic minority groups already face a disproportionate burden of cervical and breast cancers in the United States: Black women and Hispanic women have the highest rates of cervical cancer incidence (8.3 and 8.9 per 100,000 women, respectively, vs. 7.3 per 100,000 among White women) and the highest rates of cervical cancer deaths. Black women have the highest rate of breast cancer death (26.9 per 100,000 women, vs. 19.4 per 100,000 among White women), the study authors explain.

Although the volume of screening began to recover in May 2020 – test volumes for breast and cervical cancer were 39% and 40% below the 5-year average by June 2020 – breast cancer screening in rural areas remained 52% below the 5-year average, they report.

The findings were published online June 30 in Preventive Medicine.

“This study highlights a decline in cancer screening among women of racial and ethnic minority groups with low incomes when their access to medical services decreased at the beginning of the pandemic,” Dr. DeGroff comments in the CDC press release.

The findings “reinforce the need to safely maintain routine health care services during the pandemic, especially when the health care environment meets COVID-19 safety guidelines,” she adds.

The investigators used NBCCEDP administrative and program data reported to the CDC by awardees – organizations that receive funding to implement the NBCCEDP – to assess the impact of COVID-19 on the number of breast and cervical cancer screening tests administered through the program and the effects of COVID-19 on the availability of screening services and NBCCEDP awardees’ capacity to support partner clinics.

A total of 630,264 breast and 594,566 cervical cancer screening tests were conducted during the review period of January-June 2015-2020.

Despite COVID-related challenges, “a large number of awardees reported flexibility and creative efforts to reach women and support clinics’ resumption of clinical care, including screening, during the COVID-19 pandemic,” the authors write.

“[The] CDC encourages health care professionals to help minimize delays in testing by continuing routine cancer screening for women having symptoms or at high risk for breast or cervical cancer,” Dr. DeGroff commented. “The Early Detection Program can help women overcome barriers to health equity by educating them about the importance of routine screening, addressing their concerns about COVID-19 transmission, and helping them to safely access screening through interventions like patient navigation.”

Future studies will examine the effect of the pandemic on screening during the second half of 2020, when surges of COVID-19 and their timing varied geographically, they note.

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

Breast and cervical cancer screenings declined sharply in the early months of the COVID-19 pandemic, particularly among certain racial and ethnic minority groups and rural populations, notes the U.S. Centers for Disease Control and Prevention.

The new data come from the National Breast and Cervical Cancer Early Detection Program (NBCCEDP), a program that provides cancer screening services to women with low income and inadequate health insurance.

The data show that the total number of screenings funded by the NBCCEDP declined by 87% for breast cancer screening and by 84% for cervical cancer screening in April 2020 in comparison with the previous 5-year averages for that month.

The declines in breast cancer screening varied from 84% among Hispanic women to 98% among American Indian/Alaskan Native women. The declines in cervical cancer screening varied from 82% among Black women to 92% among Asian Pacific Islander women.

In April 2020, breast cancer screening declined by 86% in metro areas, 88% in urban areas, and 89% in rural areas in comparison with respective 5-year averages. For cervical cancer screenings, the corresponding declines were 85%, 77%, and 82%.

The findings are consistent with those from studies conducted in insured populations, note the authors, led by the Amy DeGroff, PhD, MPH, of the CDC’s National Center for Chronic Disease Prevention and Health Promotion.

“Prolonged delays in screening related to the COVID-19 pandemic may lead to delayed diagnoses, poor health consequences, and an increase in cancer disparities among women already experiencing health inequities,” the CDC states in a press release.

Women from racial and ethnic minority groups already face a disproportionate burden of cervical and breast cancers in the United States: Black women and Hispanic women have the highest rates of cervical cancer incidence (8.3 and 8.9 per 100,000 women, respectively, vs. 7.3 per 100,000 among White women) and the highest rates of cervical cancer deaths. Black women have the highest rate of breast cancer death (26.9 per 100,000 women, vs. 19.4 per 100,000 among White women), the study authors explain.

Although the volume of screening began to recover in May 2020 – test volumes for breast and cervical cancer were 39% and 40% below the 5-year average by June 2020 – breast cancer screening in rural areas remained 52% below the 5-year average, they report.

The findings were published online June 30 in Preventive Medicine.

“This study highlights a decline in cancer screening among women of racial and ethnic minority groups with low incomes when their access to medical services decreased at the beginning of the pandemic,” Dr. DeGroff comments in the CDC press release.

The findings “reinforce the need to safely maintain routine health care services during the pandemic, especially when the health care environment meets COVID-19 safety guidelines,” she adds.

The investigators used NBCCEDP administrative and program data reported to the CDC by awardees – organizations that receive funding to implement the NBCCEDP – to assess the impact of COVID-19 on the number of breast and cervical cancer screening tests administered through the program and the effects of COVID-19 on the availability of screening services and NBCCEDP awardees’ capacity to support partner clinics.

A total of 630,264 breast and 594,566 cervical cancer screening tests were conducted during the review period of January-June 2015-2020.

Despite COVID-related challenges, “a large number of awardees reported flexibility and creative efforts to reach women and support clinics’ resumption of clinical care, including screening, during the COVID-19 pandemic,” the authors write.

“[The] CDC encourages health care professionals to help minimize delays in testing by continuing routine cancer screening for women having symptoms or at high risk for breast or cervical cancer,” Dr. DeGroff commented. “The Early Detection Program can help women overcome barriers to health equity by educating them about the importance of routine screening, addressing their concerns about COVID-19 transmission, and helping them to safely access screening through interventions like patient navigation.”

Future studies will examine the effect of the pandemic on screening during the second half of 2020, when surges of COVID-19 and their timing varied geographically, they note.

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

With vaccination rates increasing and new infections declining, we all hope the worst of the COVID-19 pandemic is over (fingers crossed really tight). Regardless, the post–COVID-19 syndrome pandemic has already begun. What is post–COVID-19 syndrome (or long-haulers or long-COVID)? Is it standard postviral fatigue? Prolonged deconditioning following debilitating illness? Permanent lung or vascular injury? Common sense and past experience say it’s all of these.

In theory, the burden of actual lung injury post COVID-19 should be the easiest to quantify, so let’s discuss what we think we know. I’ve heard experts break post–COVID-19 lung injury into three broad categories:

• Preexisting lung disease that is exacerbated by acute COVID-19 infection.
• Acute COVID-19 infection that causes acute respiratory distress syndrome (ARDS) or other acute lung injury (ALI).
• Non–critically ill acute COVID-19 with residual lung damage and abnormal repair.

These categories are necessarily imprecise, making it challenging to fit some patients neatly into a single definition.

For patients in the first category, management will be dictated largely by the nature of the preexisting lung disease. For those in category two, we already know a lot about what their recovery from ARDS will look like. There’s no longer reason to believe that COVID-19–related ARDS is particularly unique, and all things being equal, lung recovery should mimic that seen with non–COVID-19 ARDS.

It’s going to take patience and time, and beyond targeted rehabilitation it’s not clear that we have anything available to expedite the process.

The third category of patients is the most intriguing. Is there a group of patients who have residual lung injury but didn’t have evident ARDS/ALI during their acute COVID-19 infection? Anecdotally we think so, but we know little about prevalence and less about management. A recent study published in Annals of the American Thoracic Society addresses both issues. In an observational report on patients recovering after being hospitalized with COVID-19 infection, the authors found that 3.6% of patients had residual lung injury that improved with 3 weeks of corticosteroid treatment.

The report is timely and helpful but hardly definitive. It’s observational, and patients required extensive screening and identification by a multidisciplinary committee of experts in interstitial lung disease. Patients were diagnosed as having organizing pneumonia (OP) as their “lung injury” if certain radiographic criteria were met. There were no biopsies. Last, there was no control group. Still, this report is critically important. It tells us that at 6 weeks post discharge, about 3.6% of patients who were hospitalized for COVID-19 will have persistent symptoms, radiographic abnormalities, and a plateau in their recovery.

Beyond that, it tells us little. Did these patients really have OP? It’s impossible to know. The CT findings used to establish the diagnosis are nonspecific. Response to steroids is consistent with OP, but the treatment course was quite short. If truly OP, one would expect a high relapse rate after steroid withdrawal. Patients weren’t followed long enough to monitor recurrence rates. Also, as appropriately discussed in the accompanying editorial, there’s no control group so we can’t know whether the patients treated with steroids would have recovered without treatment. There was objective improvement in lung function for the two to three patients they followed who did not receive steroids. However, it was of lesser magnitude than in the steroid group.

Post–COVID-19 symptoms will remain a challenge for the foreseeable future. More than 30 million patients have been diagnosed with COVID-19 in the United States and close to half will experience persistent dyspnea. Putting the numbers together, I conclude that the vast majority will not have identifiable lung injury that will benefit from steroids. I wish I could prescribe patience to both physicians and patients.

Dr. Holley is associate professor of medicine at Uniformed Services University and program director of pulmonary and critical care medicine at Walter Reed National Military Medical Center. He covers a wide range of topics in pulmonary, critical care, and sleep medicine.
 

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

With vaccination rates increasing and new infections declining, we all hope the worst of the COVID-19 pandemic is over (fingers crossed really tight). Regardless, the post–COVID-19 syndrome pandemic has already begun. What is post–COVID-19 syndrome (or long-haulers or long-COVID)? Is it standard postviral fatigue? Prolonged deconditioning following debilitating illness? Permanent lung or vascular injury? Common sense and past experience say it’s all of these.

In theory, the burden of actual lung injury post COVID-19 should be the easiest to quantify, so let’s discuss what we think we know. I’ve heard experts break post–COVID-19 lung injury into three broad categories:

• Preexisting lung disease that is exacerbated by acute COVID-19 infection.
• Acute COVID-19 infection that causes acute respiratory distress syndrome (ARDS) or other acute lung injury (ALI).
• Non–critically ill acute COVID-19 with residual lung damage and abnormal repair.

These categories are necessarily imprecise, making it challenging to fit some patients neatly into a single definition.

For patients in the first category, management will be dictated largely by the nature of the preexisting lung disease. For those in category two, we already know a lot about what their recovery from ARDS will look like. There’s no longer reason to believe that COVID-19–related ARDS is particularly unique, and all things being equal, lung recovery should mimic that seen with non–COVID-19 ARDS.

It’s going to take patience and time, and beyond targeted rehabilitation it’s not clear that we have anything available to expedite the process.

The third category of patients is the most intriguing. Is there a group of patients who have residual lung injury but didn’t have evident ARDS/ALI during their acute COVID-19 infection? Anecdotally we think so, but we know little about prevalence and less about management. A recent study published in Annals of the American Thoracic Society addresses both issues. In an observational report on patients recovering after being hospitalized with COVID-19 infection, the authors found that 3.6% of patients had residual lung injury that improved with 3 weeks of corticosteroid treatment.

The report is timely and helpful but hardly definitive. It’s observational, and patients required extensive screening and identification by a multidisciplinary committee of experts in interstitial lung disease. Patients were diagnosed as having organizing pneumonia (OP) as their “lung injury” if certain radiographic criteria were met. There were no biopsies. Last, there was no control group. Still, this report is critically important. It tells us that at 6 weeks post discharge, about 3.6% of patients who were hospitalized for COVID-19 will have persistent symptoms, radiographic abnormalities, and a plateau in their recovery.

Beyond that, it tells us little. Did these patients really have OP? It’s impossible to know. The CT findings used to establish the diagnosis are nonspecific. Response to steroids is consistent with OP, but the treatment course was quite short. If truly OP, one would expect a high relapse rate after steroid withdrawal. Patients weren’t followed long enough to monitor recurrence rates. Also, as appropriately discussed in the accompanying editorial, there’s no control group so we can’t know whether the patients treated with steroids would have recovered without treatment. There was objective improvement in lung function for the two to three patients they followed who did not receive steroids. However, it was of lesser magnitude than in the steroid group.

Post–COVID-19 symptoms will remain a challenge for the foreseeable future. More than 30 million patients have been diagnosed with COVID-19 in the United States and close to half will experience persistent dyspnea. Putting the numbers together, I conclude that the vast majority will not have identifiable lung injury that will benefit from steroids. I wish I could prescribe patience to both physicians and patients.

Dr. Holley is associate professor of medicine at Uniformed Services University and program director of pulmonary and critical care medicine at Walter Reed National Military Medical Center. He covers a wide range of topics in pulmonary, critical care, and sleep medicine.
 

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

With vaccination rates increasing and new infections declining, we all hope the worst of the COVID-19 pandemic is over (fingers crossed really tight). Regardless, the post–COVID-19 syndrome pandemic has already begun. What is post–COVID-19 syndrome (or long-haulers or long-COVID)? Is it standard postviral fatigue? Prolonged deconditioning following debilitating illness? Permanent lung or vascular injury? Common sense and past experience say it’s all of these.

In theory, the burden of actual lung injury post COVID-19 should be the easiest to quantify, so let’s discuss what we think we know. I’ve heard experts break post–COVID-19 lung injury into three broad categories:

• Preexisting lung disease that is exacerbated by acute COVID-19 infection.
• Acute COVID-19 infection that causes acute respiratory distress syndrome (ARDS) or other acute lung injury (ALI).
• Non–critically ill acute COVID-19 with residual lung damage and abnormal repair.

These categories are necessarily imprecise, making it challenging to fit some patients neatly into a single definition.

For patients in the first category, management will be dictated largely by the nature of the preexisting lung disease. For those in category two, we already know a lot about what their recovery from ARDS will look like. There’s no longer reason to believe that COVID-19–related ARDS is particularly unique, and all things being equal, lung recovery should mimic that seen with non–COVID-19 ARDS.

It’s going to take patience and time, and beyond targeted rehabilitation it’s not clear that we have anything available to expedite the process.

The third category of patients is the most intriguing. Is there a group of patients who have residual lung injury but didn’t have evident ARDS/ALI during their acute COVID-19 infection? Anecdotally we think so, but we know little about prevalence and less about management. A recent study published in Annals of the American Thoracic Society addresses both issues. In an observational report on patients recovering after being hospitalized with COVID-19 infection, the authors found that 3.6% of patients had residual lung injury that improved with 3 weeks of corticosteroid treatment.

The report is timely and helpful but hardly definitive. It’s observational, and patients required extensive screening and identification by a multidisciplinary committee of experts in interstitial lung disease. Patients were diagnosed as having organizing pneumonia (OP) as their “lung injury” if certain radiographic criteria were met. There were no biopsies. Last, there was no control group. Still, this report is critically important. It tells us that at 6 weeks post discharge, about 3.6% of patients who were hospitalized for COVID-19 will have persistent symptoms, radiographic abnormalities, and a plateau in their recovery.

Beyond that, it tells us little. Did these patients really have OP? It’s impossible to know. The CT findings used to establish the diagnosis are nonspecific. Response to steroids is consistent with OP, but the treatment course was quite short. If truly OP, one would expect a high relapse rate after steroid withdrawal. Patients weren’t followed long enough to monitor recurrence rates. Also, as appropriately discussed in the accompanying editorial, there’s no control group so we can’t know whether the patients treated with steroids would have recovered without treatment. There was objective improvement in lung function for the two to three patients they followed who did not receive steroids. However, it was of lesser magnitude than in the steroid group.

Post–COVID-19 symptoms will remain a challenge for the foreseeable future. More than 30 million patients have been diagnosed with COVID-19 in the United States and close to half will experience persistent dyspnea. Putting the numbers together, I conclude that the vast majority will not have identifiable lung injury that will benefit from steroids. I wish I could prescribe patience to both physicians and patients.

Dr. Holley is associate professor of medicine at Uniformed Services University and program director of pulmonary and critical care medicine at Walter Reed National Military Medical Center. He covers a wide range of topics in pulmonary, critical care, and sleep medicine.
 

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

If you, a friend, or a loved one remain unvaccinated against COVID-19 at this point – for whatever reason – you are at higher risk of dying if you become infected.

That’s the conclusion of a new report released by the Associated Press looking at COVID-19 deaths during May 2021.

Of more than 18,000 people who died from COVID-19, for example, only about 150 were fully vaccinated. That’s less than 1%.

“Recently, I was working in the emergency room [and] I saw a 21-year-old African American who came in with shortness of breath,” said Vino K. Palli, MD, MPH, a physician specializing in emergency medicine, internal medicine, and urgent care.

The patient rapidly deteriorated and required intubation and ventilation. She was transferred to a specialized hospital for possible extracorporeal membrane oxygenation (ECMO) treatment.

“This patient was unvaccinated, along with her entire family. This would have been easily preventable,” added Dr. Palli, who is also founder and CEO of MiDoctor Urgent Care in New York City.

“Vaccine misinformation, compounded with vaccine inertia and vaccine access, have contributed to this,” he added. “Even though we have a surplus amount of vaccines at this time, we are only seeing 50% to 55% of completely vaccinated patients.”

Authors of the Associated Press report also acknowledge that some people who are fully vaccinated can get a breakthrough infection. These occurred in fewer than 1,200 of more than 853,000 people hospitalized for COVID-19 in May, or about 0.1%.

The Associated Press came up with these numbers using data from the Centers for Disease Control and Prevention. The CDC tracks the numbers of cases, hospitalizations, and deaths but does not breakdown rates by vaccination status.  
 

Stronger argument for vaccination?

“The fact that only 0.8% of COVID-19 deaths are in the fully vaccinated should persuade those people still hesitant about vaccination,” said Hugh Cassiere, MD, medical director of Respiratory Therapy Services at North Shore University Hospital in Manhasset, New York.

Stuart C. Ray, MD, professor of medicine and oncology in the Division of Infectious Diseases at Johns Hopkins University, Baltimore, agreed. “It seems compelling, even for skeptics, that unvaccinated people represent 99% of those now dying from COVID-19 when they represent less than 50% of the adult population in the United States.”

The findings from the study could be more persuasive than previous arguments made in favor of immunization, Dr. Ray said. “These recent findings of striking reductions in risk of death in the vaccinated are more directly attributable and harder to ignore or dismiss.”

Brian Labus, PhD, MPH, of the University of Nevada Las Vegas (UNLV) is less convinced. “While this might change some peoples’ minds, it probably won’t make a major difference. People have many different reasons for not getting vaccinated, and this is only one of the things they consider.”

The study adds information that was not available before, said Dr. Labus, assistant professor in the Department of Epidemiology and Biostatistics at the UNLV School of Public Health. “We study the vaccine under tightly controlled, ideal conditions. This is the evidence that it works as well in the real world as it did in the trials, and that is what is most important in implementing a vaccination program,” added Dr. Labus.

“The scientific data has honed in on one thing: Vaccines are effective in preventing hospitalizations, ICU admissions, ventilations, and deaths,” agreed Dr. Palli.

“We now know that almost all deaths occurred in patients who were not vaccinated. We also know that all vaccines are effective against various strains that are in circulation right now, including the Delta variant, which is rapidly spreading,” Dr. Palli said.

Dr. Cassiere pointed out that the unvaccinated are not only at higher risk of developing COVID-19 but also of spreading, being hospitalized for, and dying from the infection. Avoiding “long hauler” symptoms is another argument in favor of immunization, he added.

As of June 28, the CDC reports that 63% of Americans 12 years and older have received at least one dose of a COVID-19 vaccine, and 54% are fully vaccinated.
 

Worldwide worry?

Although overall rates of U.S. COVID-19 hospitalizations and deaths are down, the outlook may not remain as encouraging. “I hope I’m wrong about this, but I anticipate that the coming fall and winter will bring increasingly localized versions of similar findings – severe disease and death due to SARS-CoV-2 infection in regions or groups with lower vaccination rates,” Dr. Ray said.

There could be a silver lining, he added: “If this unfortunate surge occurs, the health and economic consequences seem likely to erode much of the remaining hesitancy regarding vaccination.”

The rise of more infectious SARS-CoV-2 variants, such as the Delta variant, could also throw a wrench in controlling COVID-19. “This isn’t just a domestic issue,” Dr. Ray said. “We have learned that the world is a small place in pandemic times.”

The Associated Press investigators state that their findings support the high efficacy of the vaccine. Also, given the current widespread availability of COVID-19 vaccines in the United States, they believe many of the COVID-19 deaths now occurring are preventable.

Public health measures should have continued longer to protect unvaccinated individuals, especially Black Americans, Hispanic Americans, and other minorities, Dr. Palli said. “Only time will tell if re-opening and abandoning all public health measures by the CDC was premature.”

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

If you, a friend, or a loved one remain unvaccinated against COVID-19 at this point – for whatever reason – you are at higher risk of dying if you become infected.

That’s the conclusion of a new report released by the Associated Press looking at COVID-19 deaths during May 2021.

Of more than 18,000 people who died from COVID-19, for example, only about 150 were fully vaccinated. That’s less than 1%.

“Recently, I was working in the emergency room [and] I saw a 21-year-old African American who came in with shortness of breath,” said Vino K. Palli, MD, MPH, a physician specializing in emergency medicine, internal medicine, and urgent care.

The patient rapidly deteriorated and required intubation and ventilation. She was transferred to a specialized hospital for possible extracorporeal membrane oxygenation (ECMO) treatment.

“This patient was unvaccinated, along with her entire family. This would have been easily preventable,” added Dr. Palli, who is also founder and CEO of MiDoctor Urgent Care in New York City.

“Vaccine misinformation, compounded with vaccine inertia and vaccine access, have contributed to this,” he added. “Even though we have a surplus amount of vaccines at this time, we are only seeing 50% to 55% of completely vaccinated patients.”

Authors of the Associated Press report also acknowledge that some people who are fully vaccinated can get a breakthrough infection. These occurred in fewer than 1,200 of more than 853,000 people hospitalized for COVID-19 in May, or about 0.1%.

The Associated Press came up with these numbers using data from the Centers for Disease Control and Prevention. The CDC tracks the numbers of cases, hospitalizations, and deaths but does not breakdown rates by vaccination status.  
 

Stronger argument for vaccination?

“The fact that only 0.8% of COVID-19 deaths are in the fully vaccinated should persuade those people still hesitant about vaccination,” said Hugh Cassiere, MD, medical director of Respiratory Therapy Services at North Shore University Hospital in Manhasset, New York.

Stuart C. Ray, MD, professor of medicine and oncology in the Division of Infectious Diseases at Johns Hopkins University, Baltimore, agreed. “It seems compelling, even for skeptics, that unvaccinated people represent 99% of those now dying from COVID-19 when they represent less than 50% of the adult population in the United States.”

The findings from the study could be more persuasive than previous arguments made in favor of immunization, Dr. Ray said. “These recent findings of striking reductions in risk of death in the vaccinated are more directly attributable and harder to ignore or dismiss.”

Brian Labus, PhD, MPH, of the University of Nevada Las Vegas (UNLV) is less convinced. “While this might change some peoples’ minds, it probably won’t make a major difference. People have many different reasons for not getting vaccinated, and this is only one of the things they consider.”

The study adds information that was not available before, said Dr. Labus, assistant professor in the Department of Epidemiology and Biostatistics at the UNLV School of Public Health. “We study the vaccine under tightly controlled, ideal conditions. This is the evidence that it works as well in the real world as it did in the trials, and that is what is most important in implementing a vaccination program,” added Dr. Labus.

“The scientific data has honed in on one thing: Vaccines are effective in preventing hospitalizations, ICU admissions, ventilations, and deaths,” agreed Dr. Palli.

“We now know that almost all deaths occurred in patients who were not vaccinated. We also know that all vaccines are effective against various strains that are in circulation right now, including the Delta variant, which is rapidly spreading,” Dr. Palli said.

Dr. Cassiere pointed out that the unvaccinated are not only at higher risk of developing COVID-19 but also of spreading, being hospitalized for, and dying from the infection. Avoiding “long hauler” symptoms is another argument in favor of immunization, he added.

As of June 28, the CDC reports that 63% of Americans 12 years and older have received at least one dose of a COVID-19 vaccine, and 54% are fully vaccinated.
 

Worldwide worry?

Although overall rates of U.S. COVID-19 hospitalizations and deaths are down, the outlook may not remain as encouraging. “I hope I’m wrong about this, but I anticipate that the coming fall and winter will bring increasingly localized versions of similar findings – severe disease and death due to SARS-CoV-2 infection in regions or groups with lower vaccination rates,” Dr. Ray said.

There could be a silver lining, he added: “If this unfortunate surge occurs, the health and economic consequences seem likely to erode much of the remaining hesitancy regarding vaccination.”

The rise of more infectious SARS-CoV-2 variants, such as the Delta variant, could also throw a wrench in controlling COVID-19. “This isn’t just a domestic issue,” Dr. Ray said. “We have learned that the world is a small place in pandemic times.”

The Associated Press investigators state that their findings support the high efficacy of the vaccine. Also, given the current widespread availability of COVID-19 vaccines in the United States, they believe many of the COVID-19 deaths now occurring are preventable.

Public health measures should have continued longer to protect unvaccinated individuals, especially Black Americans, Hispanic Americans, and other minorities, Dr. Palli said. “Only time will tell if re-opening and abandoning all public health measures by the CDC was premature.”

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

If you, a friend, or a loved one remain unvaccinated against COVID-19 at this point – for whatever reason – you are at higher risk of dying if you become infected.

That’s the conclusion of a new report released by the Associated Press looking at COVID-19 deaths during May 2021.

Of more than 18,000 people who died from COVID-19, for example, only about 150 were fully vaccinated. That’s less than 1%.

“Recently, I was working in the emergency room [and] I saw a 21-year-old African American who came in with shortness of breath,” said Vino K. Palli, MD, MPH, a physician specializing in emergency medicine, internal medicine, and urgent care.

The patient rapidly deteriorated and required intubation and ventilation. She was transferred to a specialized hospital for possible extracorporeal membrane oxygenation (ECMO) treatment.

“This patient was unvaccinated, along with her entire family. This would have been easily preventable,” added Dr. Palli, who is also founder and CEO of MiDoctor Urgent Care in New York City.

“Vaccine misinformation, compounded with vaccine inertia and vaccine access, have contributed to this,” he added. “Even though we have a surplus amount of vaccines at this time, we are only seeing 50% to 55% of completely vaccinated patients.”

Authors of the Associated Press report also acknowledge that some people who are fully vaccinated can get a breakthrough infection. These occurred in fewer than 1,200 of more than 853,000 people hospitalized for COVID-19 in May, or about 0.1%.

The Associated Press came up with these numbers using data from the Centers for Disease Control and Prevention. The CDC tracks the numbers of cases, hospitalizations, and deaths but does not breakdown rates by vaccination status.  
 

Stronger argument for vaccination?

“The fact that only 0.8% of COVID-19 deaths are in the fully vaccinated should persuade those people still hesitant about vaccination,” said Hugh Cassiere, MD, medical director of Respiratory Therapy Services at North Shore University Hospital in Manhasset, New York.

Stuart C. Ray, MD, professor of medicine and oncology in the Division of Infectious Diseases at Johns Hopkins University, Baltimore, agreed. “It seems compelling, even for skeptics, that unvaccinated people represent 99% of those now dying from COVID-19 when they represent less than 50% of the adult population in the United States.”

The findings from the study could be more persuasive than previous arguments made in favor of immunization, Dr. Ray said. “These recent findings of striking reductions in risk of death in the vaccinated are more directly attributable and harder to ignore or dismiss.”

Brian Labus, PhD, MPH, of the University of Nevada Las Vegas (UNLV) is less convinced. “While this might change some peoples’ minds, it probably won’t make a major difference. People have many different reasons for not getting vaccinated, and this is only one of the things they consider.”

The study adds information that was not available before, said Dr. Labus, assistant professor in the Department of Epidemiology and Biostatistics at the UNLV School of Public Health. “We study the vaccine under tightly controlled, ideal conditions. This is the evidence that it works as well in the real world as it did in the trials, and that is what is most important in implementing a vaccination program,” added Dr. Labus.

“The scientific data has honed in on one thing: Vaccines are effective in preventing hospitalizations, ICU admissions, ventilations, and deaths,” agreed Dr. Palli.

“We now know that almost all deaths occurred in patients who were not vaccinated. We also know that all vaccines are effective against various strains that are in circulation right now, including the Delta variant, which is rapidly spreading,” Dr. Palli said.

Dr. Cassiere pointed out that the unvaccinated are not only at higher risk of developing COVID-19 but also of spreading, being hospitalized for, and dying from the infection. Avoiding “long hauler” symptoms is another argument in favor of immunization, he added.

As of June 28, the CDC reports that 63% of Americans 12 years and older have received at least one dose of a COVID-19 vaccine, and 54% are fully vaccinated.
 

Worldwide worry?

Although overall rates of U.S. COVID-19 hospitalizations and deaths are down, the outlook may not remain as encouraging. “I hope I’m wrong about this, but I anticipate that the coming fall and winter will bring increasingly localized versions of similar findings – severe disease and death due to SARS-CoV-2 infection in regions or groups with lower vaccination rates,” Dr. Ray said.

There could be a silver lining, he added: “If this unfortunate surge occurs, the health and economic consequences seem likely to erode much of the remaining hesitancy regarding vaccination.”

The rise of more infectious SARS-CoV-2 variants, such as the Delta variant, could also throw a wrench in controlling COVID-19. “This isn’t just a domestic issue,” Dr. Ray said. “We have learned that the world is a small place in pandemic times.”

The Associated Press investigators state that their findings support the high efficacy of the vaccine. Also, given the current widespread availability of COVID-19 vaccines in the United States, they believe many of the COVID-19 deaths now occurring are preventable.

Public health measures should have continued longer to protect unvaccinated individuals, especially Black Americans, Hispanic Americans, and other minorities, Dr. Palli said. “Only time will tell if re-opening and abandoning all public health measures by the CDC was premature.”

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

Fidaa Wishah, MD, a pediatric radiologist at Phoenix Children’s Hospital in Arizona, has been fired after the hospital reviewed evidence that included her anti-Israel comments on social media, according to the hospital’s statement.

On May 26, Dr. Wishah posted, “We will uncover your thirst to kill our Palestinian children. … We sense your fear. The fear of your collapse. A state based on atrocity, inhumanity, racism and cannibalism never last long! Hey #israel … your end is coming sooner than you think.”

Phoenix Children’s Hospital did not respond to this news organization’s request for comment but said in a statement to the Jewish News Syndicate : “After a thorough review of the facts related to this matter, this individual is no longer providing care at Phoenix Children’s. All children in the care of Phoenix Children’s receive hope, healing and the best possible health care, regardless of race, color, disability, religion, gender, gender identity, sexual orientation or national origin.”

Dr. Wishah’s profile has been removed from the hospital website. Her LinkedIn profile indicates she had been a pediatric radiology fellow at Stanford (Calif.) University, specializing in advanced magnetic resonance imaging and fetal imaging and had been a senior staff pediatric radiologist at Henry Ford Health System in Detroit.

It wasn’t the first time antisemitic comments have led to the firing of a physician. Last year, this news organization wrote about Lara Kollab, DO, a first-year resident fired for her antisemitic tweets. She was subsequently barred from medicine.

In the same post from May 26, Dr. Wishah also wrote: “We will not be #censored anymore! Bomb our media buildings and we have the phones[.] Bribe the mainstream media and we have our small #socialmedia platforms[.] From our windows ... from our streets ... next the rubble we will expose you to the world[.] We will expose the #massacre and #genocide you #zionists are proud of[.]”

Today, CAIR-AZ, a group whose mission is to “enhance understanding of Islam, protect civil rights, promote justice, and empower American Muslims,” according to its website, announced that it, along with three private law firms, will represent Dr. Wishah in what they referred to as “her wrongful termination case against Phoenix Children’s Hospital.”

The announcement, which mentions that Dr. Wishah was born and raised in Gaza, said, “Dr. Wishah has been a medical doctor since 2010 and has spent the vast majority of her career as a pediatric physician. Despite caring for thousands of children, many of whom are Jewish, she has never been accused of discriminating against any of her patients or colleagues.”

The statement added, “PCH’s decision to terminate Dr. Wishah is shameful and an attack on freedom of speech.”

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

Fidaa Wishah, MD, a pediatric radiologist at Phoenix Children’s Hospital in Arizona, has been fired after the hospital reviewed evidence that included her anti-Israel comments on social media, according to the hospital’s statement.

On May 26, Dr. Wishah posted, “We will uncover your thirst to kill our Palestinian children. … We sense your fear. The fear of your collapse. A state based on atrocity, inhumanity, racism and cannibalism never last long! Hey #israel … your end is coming sooner than you think.”

Phoenix Children’s Hospital did not respond to this news organization’s request for comment but said in a statement to the Jewish News Syndicate : “After a thorough review of the facts related to this matter, this individual is no longer providing care at Phoenix Children’s. All children in the care of Phoenix Children’s receive hope, healing and the best possible health care, regardless of race, color, disability, religion, gender, gender identity, sexual orientation or national origin.”

Dr. Wishah’s profile has been removed from the hospital website. Her LinkedIn profile indicates she had been a pediatric radiology fellow at Stanford (Calif.) University, specializing in advanced magnetic resonance imaging and fetal imaging and had been a senior staff pediatric radiologist at Henry Ford Health System in Detroit.

It wasn’t the first time antisemitic comments have led to the firing of a physician. Last year, this news organization wrote about Lara Kollab, DO, a first-year resident fired for her antisemitic tweets. She was subsequently barred from medicine.

In the same post from May 26, Dr. Wishah also wrote: “We will not be #censored anymore! Bomb our media buildings and we have the phones[.] Bribe the mainstream media and we have our small #socialmedia platforms[.] From our windows ... from our streets ... next the rubble we will expose you to the world[.] We will expose the #massacre and #genocide you #zionists are proud of[.]”

Today, CAIR-AZ, a group whose mission is to “enhance understanding of Islam, protect civil rights, promote justice, and empower American Muslims,” according to its website, announced that it, along with three private law firms, will represent Dr. Wishah in what they referred to as “her wrongful termination case against Phoenix Children’s Hospital.”

The announcement, which mentions that Dr. Wishah was born and raised in Gaza, said, “Dr. Wishah has been a medical doctor since 2010 and has spent the vast majority of her career as a pediatric physician. Despite caring for thousands of children, many of whom are Jewish, she has never been accused of discriminating against any of her patients or colleagues.”

The statement added, “PCH’s decision to terminate Dr. Wishah is shameful and an attack on freedom of speech.”

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

Fidaa Wishah, MD, a pediatric radiologist at Phoenix Children’s Hospital in Arizona, has been fired after the hospital reviewed evidence that included her anti-Israel comments on social media, according to the hospital’s statement.

On May 26, Dr. Wishah posted, “We will uncover your thirst to kill our Palestinian children. … We sense your fear. The fear of your collapse. A state based on atrocity, inhumanity, racism and cannibalism never last long! Hey #israel … your end is coming sooner than you think.”

Phoenix Children’s Hospital did not respond to this news organization’s request for comment but said in a statement to the Jewish News Syndicate : “After a thorough review of the facts related to this matter, this individual is no longer providing care at Phoenix Children’s. All children in the care of Phoenix Children’s receive hope, healing and the best possible health care, regardless of race, color, disability, religion, gender, gender identity, sexual orientation or national origin.”

Dr. Wishah’s profile has been removed from the hospital website. Her LinkedIn profile indicates she had been a pediatric radiology fellow at Stanford (Calif.) University, specializing in advanced magnetic resonance imaging and fetal imaging and had been a senior staff pediatric radiologist at Henry Ford Health System in Detroit.

It wasn’t the first time antisemitic comments have led to the firing of a physician. Last year, this news organization wrote about Lara Kollab, DO, a first-year resident fired for her antisemitic tweets. She was subsequently barred from medicine.

In the same post from May 26, Dr. Wishah also wrote: “We will not be #censored anymore! Bomb our media buildings and we have the phones[.] Bribe the mainstream media and we have our small #socialmedia platforms[.] From our windows ... from our streets ... next the rubble we will expose you to the world[.] We will expose the #massacre and #genocide you #zionists are proud of[.]”

Today, CAIR-AZ, a group whose mission is to “enhance understanding of Islam, protect civil rights, promote justice, and empower American Muslims,” according to its website, announced that it, along with three private law firms, will represent Dr. Wishah in what they referred to as “her wrongful termination case against Phoenix Children’s Hospital.”

The announcement, which mentions that Dr. Wishah was born and raised in Gaza, said, “Dr. Wishah has been a medical doctor since 2010 and has spent the vast majority of her career as a pediatric physician. Despite caring for thousands of children, many of whom are Jewish, she has never been accused of discriminating against any of her patients or colleagues.”

The statement added, “PCH’s decision to terminate Dr. Wishah is shameful and an attack on freedom of speech.”

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

Data from a large French registry on a multicenter experience with chimeric antigen receptor T-cell (CAR T) therapy for aggressive lymphoma suggests that the favorable outcomes seen in clinical trials can be replicated in the real world.

Among 481 patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) treated with either of two commercially available CAR T products – tisagenlecleucel (Kymriah) or axicabtagene ciloleucel (Yescarta) – the duration of responses, progression-free survival (PFS), and overall survival (OS) rates at 6 months mirror those seen in clinical trials, reported Steven LeGouill, MD, PhD, from the University of Nantes (France), on behalf of colleagues in the DESCAR-T (Dispositive d’Evaluation et de Suivi des CAR-T) registry.

“CAR T has now become a standard of care in a lot of French centers, with more than 640 patients treated with CAR T in less than 2 years. The DESCAR-T real-life experience mimics the experience that had been previously by other real-life registries but also in clinical trials. We didn’t see new emerging toxicity signals in real life,” he said in an oral abstract session during the European Hematology Association annual congress (Abstract S216).

“I am convinced that a population registry about CAR T–treated patients is needed,” commented Pieter Sonneveld, MD, from Erasmus Medical Center in Rotterdam, the Netherlands, who was not involved in the study.

“Selection criteria for CAR T trials have been incredibly restrictive, and academic trials have not gained ground yet. It is important to collect and analyze more data, include non-trial patients and analyze long-term follow-up in order to determine the real effects of this innovative treatment in lymphoma and other diseases,” he said.

Dr. Sonneveld, EHA past president, was the moderator a briefing where Dr. LeGouill presented the DESCAR-T study findings.

Natalie Sophia Grover, MD, a leukemia and lymphoma specialist at the University of North Carolina at Chapel Hill, noted in an interview that “there have been several publications recently that have shown that these promising outcomes for these really refractory, high-risk patients with diffuse large B-cell lymphoma seem to be similar with what we’ve seen in trials, which is definitely exciting.”

She noted that the median time from CAR T order to treatment in the study, 50 days, was longer than in her experience.

“Generally, from collection to treatment is less than a month. Looking at that, I would have expected more patients not to make it CAR T, but nearly 90% of patients who had collections got treatment, which is pretty good. Those patients that didn’t make it to treatment had really poor outcomes,” she said.

Dr. Grover was not involved in the study.
 

More data, s’il vous plait

The DESCAR-T registry was created in response to a request from French health authorities for data beyond that provided in the EBMT patient registry. The health authorities asked for characterization of the CAR T–eligible population in an intention to treat, 15-year follow-up of both CAR T recipients and candidates who were not treated for whatever reasons, and a full accounting of previous lines of therapy.

Dr. LeGouill presented the first analysis of data from the registry involving 19 enrolling site and 647 patients with DLBCL for whom CAR T cells were ordered from January 2018 to March 2021.

Of the 647 candidates, 10 did not have CAR T ordered for reasons that included patient deaths or disease progression, infection, and patient refusal. An additional 30 patients either had leukapheresis performed or pending, and 607 had CAR T ordered.

Of the 607 patients, 53 did not receive CAR T infusions because of disease progression, death before product administration, manufacturing or leukapheresis failures, uncontrolled infections, patient choice, or progression of other malignancies.

That left 550 patients (85%) who received a CAR T product, either tisagenlecleucel (200 patients) or axicabtagene ciloleucel (350 patients).

Among all patients, the median age at CAR T order was 63 for patients who received tisagenlecleucel, and 65 for patients receiving axicabtagene ciloleucel. Patients 65 and older comprised 44% and 51% of the population, respectively.

Patients treated with each CAR T product had a median of three prior lines of therapy.
 

Manageable toxicities

Toxicities within 10 days of CAR T infusion included 418 cases among 515 patients (81.2%) of cytokine release syndrome, with most being grade 1 or 2 in severity; 44 patients had grade 3 or 4 CRS.

Any-grade neurotoxicity was seen in 184 patients (35.7%), primarily grade 1 or 2 in severity; 50 patients had grade 3 or greater neurotoxicity.

Of 427 patients with at least one CAR T–specific toxicity within 10 days, 139 (32.8%) required ICU admission, 325 (76,1%) were treated for CAR T–specific toxicities, 278 (65.1%) received tocilizumab, 13 (3%) received siltuximab, and 176 (41.2%) received corticosteroids.
 

Favorable outcomes

Overall response rates, at 1, 3, and 6 months post infusions were 70.6%, 56.3%, and 60%, respectively, with the majority of response at each time point being complete responses (CR).

The 6-month overall survival (OS) rate among all patients who were treated was 83.7%, compared with 5.5% for patients who did not receive CAR T infusions.

Progression-free survival (PFS) at 6 months was 44.5%, and 57.7% of patients had an ongoing response at the same time point.

Among patients who received bridging therapy between leukapheresis and CAR T infusion, the 6-month PFS was 58.4% for patients with either a CR, partial response, or stable disease, compared with 63.3% for patients who did not receive bridging therapy, and 29.8% for those with disease progression.

The respective 6 months OS rates were 87.4%, 82.3%, and 65.5%.

The results showed that patients who do not have at least stable disease at the time of CAR T infusion are at risk for early relapse, but approximately 30% of these patients still had long-term disease control, Dr. LeGouill said.

He acknowledged that longer follow-up will be need to see whether the plateaus in the PFS and OS curves the investigators observed can be maintained over time. Questions that still need to be answered include the impact of bridging therapy or disease status at the start of treatment on outcomes, and how to improve CAR T efficacy based on individual patient characteristics.

The registry will be extended to include data on patients treated with CAR T for mantle cell lymphoma and multiple myeloma, investigators announced.

The study is supported by participating centers and Gilead/Kite and Novartis. Dr. LeGouill disclosed advisory board activity and honoraria from the companies and others. Dr. Grover disclosed advisory board participating for Kite and others. Dr. Sonneveld has disclosed research grants and honoraria from several companies, not including Kite or Novartis.

Data from a large French registry on a multicenter experience with chimeric antigen receptor T-cell (CAR T) therapy for aggressive lymphoma suggests that the favorable outcomes seen in clinical trials can be replicated in the real world.

Among 481 patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) treated with either of two commercially available CAR T products – tisagenlecleucel (Kymriah) or axicabtagene ciloleucel (Yescarta) – the duration of responses, progression-free survival (PFS), and overall survival (OS) rates at 6 months mirror those seen in clinical trials, reported Steven LeGouill, MD, PhD, from the University of Nantes (France), on behalf of colleagues in the DESCAR-T (Dispositive d’Evaluation et de Suivi des CAR-T) registry.

“CAR T has now become a standard of care in a lot of French centers, with more than 640 patients treated with CAR T in less than 2 years. The DESCAR-T real-life experience mimics the experience that had been previously by other real-life registries but also in clinical trials. We didn’t see new emerging toxicity signals in real life,” he said in an oral abstract session during the European Hematology Association annual congress (Abstract S216).

“I am convinced that a population registry about CAR T–treated patients is needed,” commented Pieter Sonneveld, MD, from Erasmus Medical Center in Rotterdam, the Netherlands, who was not involved in the study.

“Selection criteria for CAR T trials have been incredibly restrictive, and academic trials have not gained ground yet. It is important to collect and analyze more data, include non-trial patients and analyze long-term follow-up in order to determine the real effects of this innovative treatment in lymphoma and other diseases,” he said.

Dr. Sonneveld, EHA past president, was the moderator a briefing where Dr. LeGouill presented the DESCAR-T study findings.

Natalie Sophia Grover, MD, a leukemia and lymphoma specialist at the University of North Carolina at Chapel Hill, noted in an interview that “there have been several publications recently that have shown that these promising outcomes for these really refractory, high-risk patients with diffuse large B-cell lymphoma seem to be similar with what we’ve seen in trials, which is definitely exciting.”

She noted that the median time from CAR T order to treatment in the study, 50 days, was longer than in her experience.

“Generally, from collection to treatment is less than a month. Looking at that, I would have expected more patients not to make it CAR T, but nearly 90% of patients who had collections got treatment, which is pretty good. Those patients that didn’t make it to treatment had really poor outcomes,” she said.

Dr. Grover was not involved in the study.
 

More data, s’il vous plait

The DESCAR-T registry was created in response to a request from French health authorities for data beyond that provided in the EBMT patient registry. The health authorities asked for characterization of the CAR T–eligible population in an intention to treat, 15-year follow-up of both CAR T recipients and candidates who were not treated for whatever reasons, and a full accounting of previous lines of therapy.

Dr. LeGouill presented the first analysis of data from the registry involving 19 enrolling site and 647 patients with DLBCL for whom CAR T cells were ordered from January 2018 to March 2021.

Of the 647 candidates, 10 did not have CAR T ordered for reasons that included patient deaths or disease progression, infection, and patient refusal. An additional 30 patients either had leukapheresis performed or pending, and 607 had CAR T ordered.

Of the 607 patients, 53 did not receive CAR T infusions because of disease progression, death before product administration, manufacturing or leukapheresis failures, uncontrolled infections, patient choice, or progression of other malignancies.

That left 550 patients (85%) who received a CAR T product, either tisagenlecleucel (200 patients) or axicabtagene ciloleucel (350 patients).

Among all patients, the median age at CAR T order was 63 for patients who received tisagenlecleucel, and 65 for patients receiving axicabtagene ciloleucel. Patients 65 and older comprised 44% and 51% of the population, respectively.

Patients treated with each CAR T product had a median of three prior lines of therapy.
 

Manageable toxicities

Toxicities within 10 days of CAR T infusion included 418 cases among 515 patients (81.2%) of cytokine release syndrome, with most being grade 1 or 2 in severity; 44 patients had grade 3 or 4 CRS.

Any-grade neurotoxicity was seen in 184 patients (35.7%), primarily grade 1 or 2 in severity; 50 patients had grade 3 or greater neurotoxicity.

Of 427 patients with at least one CAR T–specific toxicity within 10 days, 139 (32.8%) required ICU admission, 325 (76,1%) were treated for CAR T–specific toxicities, 278 (65.1%) received tocilizumab, 13 (3%) received siltuximab, and 176 (41.2%) received corticosteroids.
 

Favorable outcomes

Overall response rates, at 1, 3, and 6 months post infusions were 70.6%, 56.3%, and 60%, respectively, with the majority of response at each time point being complete responses (CR).

The 6-month overall survival (OS) rate among all patients who were treated was 83.7%, compared with 5.5% for patients who did not receive CAR T infusions.

Progression-free survival (PFS) at 6 months was 44.5%, and 57.7% of patients had an ongoing response at the same time point.

Among patients who received bridging therapy between leukapheresis and CAR T infusion, the 6-month PFS was 58.4% for patients with either a CR, partial response, or stable disease, compared with 63.3% for patients who did not receive bridging therapy, and 29.8% for those with disease progression.

The respective 6 months OS rates were 87.4%, 82.3%, and 65.5%.

The results showed that patients who do not have at least stable disease at the time of CAR T infusion are at risk for early relapse, but approximately 30% of these patients still had long-term disease control, Dr. LeGouill said.

He acknowledged that longer follow-up will be need to see whether the plateaus in the PFS and OS curves the investigators observed can be maintained over time. Questions that still need to be answered include the impact of bridging therapy or disease status at the start of treatment on outcomes, and how to improve CAR T efficacy based on individual patient characteristics.

The registry will be extended to include data on patients treated with CAR T for mantle cell lymphoma and multiple myeloma, investigators announced.

The study is supported by participating centers and Gilead/Kite and Novartis. Dr. LeGouill disclosed advisory board activity and honoraria from the companies and others. Dr. Grover disclosed advisory board participating for Kite and others. Dr. Sonneveld has disclosed research grants and honoraria from several companies, not including Kite or Novartis.

Data from a large French registry on a multicenter experience with chimeric antigen receptor T-cell (CAR T) therapy for aggressive lymphoma suggests that the favorable outcomes seen in clinical trials can be replicated in the real world.

Among 481 patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) treated with either of two commercially available CAR T products – tisagenlecleucel (Kymriah) or axicabtagene ciloleucel (Yescarta) – the duration of responses, progression-free survival (PFS), and overall survival (OS) rates at 6 months mirror those seen in clinical trials, reported Steven LeGouill, MD, PhD, from the University of Nantes (France), on behalf of colleagues in the DESCAR-T (Dispositive d’Evaluation et de Suivi des CAR-T) registry.

“CAR T has now become a standard of care in a lot of French centers, with more than 640 patients treated with CAR T in less than 2 years. The DESCAR-T real-life experience mimics the experience that had been previously by other real-life registries but also in clinical trials. We didn’t see new emerging toxicity signals in real life,” he said in an oral abstract session during the European Hematology Association annual congress (Abstract S216).

“I am convinced that a population registry about CAR T–treated patients is needed,” commented Pieter Sonneveld, MD, from Erasmus Medical Center in Rotterdam, the Netherlands, who was not involved in the study.

“Selection criteria for CAR T trials have been incredibly restrictive, and academic trials have not gained ground yet. It is important to collect and analyze more data, include non-trial patients and analyze long-term follow-up in order to determine the real effects of this innovative treatment in lymphoma and other diseases,” he said.

Dr. Sonneveld, EHA past president, was the moderator a briefing where Dr. LeGouill presented the DESCAR-T study findings.

Natalie Sophia Grover, MD, a leukemia and lymphoma specialist at the University of North Carolina at Chapel Hill, noted in an interview that “there have been several publications recently that have shown that these promising outcomes for these really refractory, high-risk patients with diffuse large B-cell lymphoma seem to be similar with what we’ve seen in trials, which is definitely exciting.”

She noted that the median time from CAR T order to treatment in the study, 50 days, was longer than in her experience.

“Generally, from collection to treatment is less than a month. Looking at that, I would have expected more patients not to make it CAR T, but nearly 90% of patients who had collections got treatment, which is pretty good. Those patients that didn’t make it to treatment had really poor outcomes,” she said.

Dr. Grover was not involved in the study.
 

More data, s’il vous plait

The DESCAR-T registry was created in response to a request from French health authorities for data beyond that provided in the EBMT patient registry. The health authorities asked for characterization of the CAR T–eligible population in an intention to treat, 15-year follow-up of both CAR T recipients and candidates who were not treated for whatever reasons, and a full accounting of previous lines of therapy.

Dr. LeGouill presented the first analysis of data from the registry involving 19 enrolling site and 647 patients with DLBCL for whom CAR T cells were ordered from January 2018 to March 2021.

Of the 647 candidates, 10 did not have CAR T ordered for reasons that included patient deaths or disease progression, infection, and patient refusal. An additional 30 patients either had leukapheresis performed or pending, and 607 had CAR T ordered.

Of the 607 patients, 53 did not receive CAR T infusions because of disease progression, death before product administration, manufacturing or leukapheresis failures, uncontrolled infections, patient choice, or progression of other malignancies.

That left 550 patients (85%) who received a CAR T product, either tisagenlecleucel (200 patients) or axicabtagene ciloleucel (350 patients).

Among all patients, the median age at CAR T order was 63 for patients who received tisagenlecleucel, and 65 for patients receiving axicabtagene ciloleucel. Patients 65 and older comprised 44% and 51% of the population, respectively.

Patients treated with each CAR T product had a median of three prior lines of therapy.
 

Manageable toxicities

Toxicities within 10 days of CAR T infusion included 418 cases among 515 patients (81.2%) of cytokine release syndrome, with most being grade 1 or 2 in severity; 44 patients had grade 3 or 4 CRS.

Any-grade neurotoxicity was seen in 184 patients (35.7%), primarily grade 1 or 2 in severity; 50 patients had grade 3 or greater neurotoxicity.

Of 427 patients with at least one CAR T–specific toxicity within 10 days, 139 (32.8%) required ICU admission, 325 (76,1%) were treated for CAR T–specific toxicities, 278 (65.1%) received tocilizumab, 13 (3%) received siltuximab, and 176 (41.2%) received corticosteroids.
 

Favorable outcomes

Overall response rates, at 1, 3, and 6 months post infusions were 70.6%, 56.3%, and 60%, respectively, with the majority of response at each time point being complete responses (CR).

The 6-month overall survival (OS) rate among all patients who were treated was 83.7%, compared with 5.5% for patients who did not receive CAR T infusions.

Progression-free survival (PFS) at 6 months was 44.5%, and 57.7% of patients had an ongoing response at the same time point.

Among patients who received bridging therapy between leukapheresis and CAR T infusion, the 6-month PFS was 58.4% for patients with either a CR, partial response, or stable disease, compared with 63.3% for patients who did not receive bridging therapy, and 29.8% for those with disease progression.

The respective 6 months OS rates were 87.4%, 82.3%, and 65.5%.

The results showed that patients who do not have at least stable disease at the time of CAR T infusion are at risk for early relapse, but approximately 30% of these patients still had long-term disease control, Dr. LeGouill said.

He acknowledged that longer follow-up will be need to see whether the plateaus in the PFS and OS curves the investigators observed can be maintained over time. Questions that still need to be answered include the impact of bridging therapy or disease status at the start of treatment on outcomes, and how to improve CAR T efficacy based on individual patient characteristics.

The registry will be extended to include data on patients treated with CAR T for mantle cell lymphoma and multiple myeloma, investigators announced.

The study is supported by participating centers and Gilead/Kite and Novartis. Dr. LeGouill disclosed advisory board activity and honoraria from the companies and others. Dr. Grover disclosed advisory board participating for Kite and others. Dr. Sonneveld has disclosed research grants and honoraria from several companies, not including Kite or Novartis.

For adults with Philadelphia chromosome–positive acute lymphoblastic leukemia (Ph+ALL), frontline therapy with the chemotherapy-free combination of ponatinib (Iclusig) and blinatumomab (Blincyto) shows promise as an alternative to early hematopoietic stem cell transplantation (HSCT), investigators in a single-arm phase 2 study reported.

In an interim analysis of the combination in patients with newly diagnosed or relapsed/refractory Ph+ALL or lymphoid accelerated or blast phase chronic myeloid leukemia (CML), 20 patients who received it as frontline therapy had a rate of complete responses (CR) or complete responses with partial recovery of blood counts (CRp) of 100% and a complete molecular remission (CMR) rate of 85%, reported Nicholas Short, MD, of the University of Texas MD Anderson Cancer Center in Houston.

“This translated into an estimated 2-year overall survival of 93%, with no patients undergoing transplant in first remission, and none having relapse at last follow-up,” he said in an oral abstract presented during the European Hematology Association annual congress.

Among patients with relapsed/refractory Ph+ALL, the CR/CRp rate was 89%, the CMR rate was 88%, and the estimated 2-year overall survival rate was 53%, he said.
 

Transplants on hold

“The big selling point is the ability to avoid stem cell transplant, which is not always the first thing you do in Ph-positive ALL, but it’s always on your mind,” said Gwen Nichols, MD, chief medical officer of the Leukemia and Lymphoma Society, who was not involved in the study.

“It looks, albeit with very limited follow-up, that patients haven’t relapsed yet such that transplant would be necessary. Anything we can do to avoid people having long-term complications that go along with an allogeneic transplant is a step in the right direction,” she said in an interview.
 

One combination, three cohorts

Ph+ALL comprises about 25% of all adult ALL. The standard of care in newly diagnosed patients is chemotherapy plus a tyrosine kinase inhibitor (TKI) targeted against the BCR-ABL transcript.

Ponatinib is a pan-BCR-ABL TKI that has been shown to have activity against ALL with T315I mutations, which are present in about 75% of the cases of relapsed disease, Dr. Short said.

Blinatumomab is a bi-specific T-cell engager (BiTe) that has been shown to be effective as monotherapy against relapsed/refractory Ph+ALL as monotherapy and in combination with dasatinib.

Dr. Short and colleagues enrolled patients with newly diagnosed or relapsed/refractory Ph+ALL or lymphoid accelerated or blast phase CML. Patients in the frontline cohort could have received one or two prior lines of chemotherapy with or without a TKI.

The patients all had Eastern Cooperative Oncology Group performance status of 0-2, and adequate liver function.

Patients with clinically significant cardiovascular disease or central nervous system disease pathology were excluded, except that patients with CNS leukemia could be enrolled.

The induction phase consisted of 30 mg ponatinib daily plus blinatumomab standard dosing on a 4-week-on, 2-week-off schedule. Patients in CMR, defined for frontline patients as undetectable BCR-ABL transcripts by polymerase chain reaction, then received up to four consolidation cycles of the regimen with ponatinib at a 15-mg dose, followed by 5 years of ponatinib 15-mg maintenance. All patients also received CNS prophylaxis with 12 cycles of intrathecal chemotherapy with alternating administration of methotrexate and cytarabine.

Of the 35 patients treated to date with the combination, 20 with Ph+ALL received it as frontline therapy and 10 received it for relapsed/refractory disease; 5 patients with CML in lymphoid blast phase also were treated.
 

High CMR, CR rates

As noted before, the CMR rate, the primary endpoint among patients with newly diagnosed Ph+ALL, was 85%, with a CR/CRp rate of 100%. Six of the patients in the frontline group and one in the salvage therapy group had CRs but were positive for minimal residual disease (MRD) at study outset.

The CR/CRp rate for the entire cohort of 28 patients (excluding those with a CR at start) was 96%, with only 1 patient who had relapsed/refractory disease not having a CR. This patient had received ponatinib in a prior salvage regimen.

The CMR rate among the entire cohort was 79%, with 85% of patients in the frontline ALL cohort having a CMR, 88% in the relapsed/refractory cohort, and 40% in the CML cohort. There were no early deaths among any patients.

“After one cycle of ponatinib plus blinatumomab, 84% of frontline patients had achieved at least a major molecular response, and 58% had achieved a CMR. Among those with relapsed/refractory Ph+ALL, 75% achieved CMR after one cycle of therapy,” Dr. Short said.

Of the 20 frontline patients in CR, one patient experienced visual changes and possible stroke that were considered possibly related to the study medication. This patient was taken off study. During a later maintenance regimen this patient developed a non-ST elevation myocardial infarction and died from postprocedural bleeding and hypovolemic shock following a cardiac catheterization procedure.

The remainder of patients in the frontline cohort had ongoing responses without the need for HSCT at last follow-up. There were no relapses, with a median duration of CR of 6 months,

Among the 10 with relapsed/refractory Ph+ALL, one did not have a response, and the remaining 9 had CR/CRps.

Of the latter groups, four went on to allogeneic HSCT and three were still alive; one patient who underwent a transplant experienced a relapse and died. One additional patient was alive with relapsed disease with T315I and E255V mutations at the time of relapse, one patient in CR who went off study due to insurance issues died from an unknown cause, and the three remaining patients had ongoing responses without transplant.

Among the five patients with CML in lymphoid blast phase, two had relapses, but both are still alive and currently in remission, and three have ongoing responses without transplant.

After a median follow-up of 12 months the 1-year event-free survival (EFS) rate for the entire 35-patient group was 76%, and the 2-year EFS was 70%.

The 1-year overall survival rate was 93%, and the 2-year OS rate was 80%.

Among patients in the frontline group, the 1-year and 2-year EFS and OS rates were all 93%.

For the relapsed/refractory cohort, the estimated 2-year EFS was 41% and OS was 53%. For the CML cohort, the 2-year EFS was 60%, with all patients still alive at last follow-up.

There were no grade 4 adverse events on study. Grade 3 adverse events considered at least possibly related to study treatment were elevated lipase, fever/febrile neutropenia, increased alanine aminotransferase, cerebrovascular ischemia, hypertension, pancreatitis, deep vein thrombosis, and encephalopathy. There were no cases of grade 3 cytokine release syndrome or tremor.

The study was sponsored by MD Anderson Cancer Center with collaboration from the National Cancer Institute, Amgen, and Takeda. Dr. Short has disclosed relationships with Amgen and Takeda. Dr. Nichols reported having no conflicts of interest.

For adults with Philadelphia chromosome–positive acute lymphoblastic leukemia (Ph+ALL), frontline therapy with the chemotherapy-free combination of ponatinib (Iclusig) and blinatumomab (Blincyto) shows promise as an alternative to early hematopoietic stem cell transplantation (HSCT), investigators in a single-arm phase 2 study reported.

In an interim analysis of the combination in patients with newly diagnosed or relapsed/refractory Ph+ALL or lymphoid accelerated or blast phase chronic myeloid leukemia (CML), 20 patients who received it as frontline therapy had a rate of complete responses (CR) or complete responses with partial recovery of blood counts (CRp) of 100% and a complete molecular remission (CMR) rate of 85%, reported Nicholas Short, MD, of the University of Texas MD Anderson Cancer Center in Houston.

“This translated into an estimated 2-year overall survival of 93%, with no patients undergoing transplant in first remission, and none having relapse at last follow-up,” he said in an oral abstract presented during the European Hematology Association annual congress.

Among patients with relapsed/refractory Ph+ALL, the CR/CRp rate was 89%, the CMR rate was 88%, and the estimated 2-year overall survival rate was 53%, he said.
 

Transplants on hold

“The big selling point is the ability to avoid stem cell transplant, which is not always the first thing you do in Ph-positive ALL, but it’s always on your mind,” said Gwen Nichols, MD, chief medical officer of the Leukemia and Lymphoma Society, who was not involved in the study.

“It looks, albeit with very limited follow-up, that patients haven’t relapsed yet such that transplant would be necessary. Anything we can do to avoid people having long-term complications that go along with an allogeneic transplant is a step in the right direction,” she said in an interview.
 

One combination, three cohorts

Ph+ALL comprises about 25% of all adult ALL. The standard of care in newly diagnosed patients is chemotherapy plus a tyrosine kinase inhibitor (TKI) targeted against the BCR-ABL transcript.

Ponatinib is a pan-BCR-ABL TKI that has been shown to have activity against ALL with T315I mutations, which are present in about 75% of the cases of relapsed disease, Dr. Short said.

Blinatumomab is a bi-specific T-cell engager (BiTe) that has been shown to be effective as monotherapy against relapsed/refractory Ph+ALL as monotherapy and in combination with dasatinib.

Dr. Short and colleagues enrolled patients with newly diagnosed or relapsed/refractory Ph+ALL or lymphoid accelerated or blast phase CML. Patients in the frontline cohort could have received one or two prior lines of chemotherapy with or without a TKI.

The patients all had Eastern Cooperative Oncology Group performance status of 0-2, and adequate liver function.

Patients with clinically significant cardiovascular disease or central nervous system disease pathology were excluded, except that patients with CNS leukemia could be enrolled.

The induction phase consisted of 30 mg ponatinib daily plus blinatumomab standard dosing on a 4-week-on, 2-week-off schedule. Patients in CMR, defined for frontline patients as undetectable BCR-ABL transcripts by polymerase chain reaction, then received up to four consolidation cycles of the regimen with ponatinib at a 15-mg dose, followed by 5 years of ponatinib 15-mg maintenance. All patients also received CNS prophylaxis with 12 cycles of intrathecal chemotherapy with alternating administration of methotrexate and cytarabine.

Of the 35 patients treated to date with the combination, 20 with Ph+ALL received it as frontline therapy and 10 received it for relapsed/refractory disease; 5 patients with CML in lymphoid blast phase also were treated.
 

High CMR, CR rates

As noted before, the CMR rate, the primary endpoint among patients with newly diagnosed Ph+ALL, was 85%, with a CR/CRp rate of 100%. Six of the patients in the frontline group and one in the salvage therapy group had CRs but were positive for minimal residual disease (MRD) at study outset.

The CR/CRp rate for the entire cohort of 28 patients (excluding those with a CR at start) was 96%, with only 1 patient who had relapsed/refractory disease not having a CR. This patient had received ponatinib in a prior salvage regimen.

The CMR rate among the entire cohort was 79%, with 85% of patients in the frontline ALL cohort having a CMR, 88% in the relapsed/refractory cohort, and 40% in the CML cohort. There were no early deaths among any patients.

“After one cycle of ponatinib plus blinatumomab, 84% of frontline patients had achieved at least a major molecular response, and 58% had achieved a CMR. Among those with relapsed/refractory Ph+ALL, 75% achieved CMR after one cycle of therapy,” Dr. Short said.

Of the 20 frontline patients in CR, one patient experienced visual changes and possible stroke that were considered possibly related to the study medication. This patient was taken off study. During a later maintenance regimen this patient developed a non-ST elevation myocardial infarction and died from postprocedural bleeding and hypovolemic shock following a cardiac catheterization procedure.

The remainder of patients in the frontline cohort had ongoing responses without the need for HSCT at last follow-up. There were no relapses, with a median duration of CR of 6 months,

Among the 10 with relapsed/refractory Ph+ALL, one did not have a response, and the remaining 9 had CR/CRps.

Of the latter groups, four went on to allogeneic HSCT and three were still alive; one patient who underwent a transplant experienced a relapse and died. One additional patient was alive with relapsed disease with T315I and E255V mutations at the time of relapse, one patient in CR who went off study due to insurance issues died from an unknown cause, and the three remaining patients had ongoing responses without transplant.

Among the five patients with CML in lymphoid blast phase, two had relapses, but both are still alive and currently in remission, and three have ongoing responses without transplant.

After a median follow-up of 12 months the 1-year event-free survival (EFS) rate for the entire 35-patient group was 76%, and the 2-year EFS was 70%.

The 1-year overall survival rate was 93%, and the 2-year OS rate was 80%.

Among patients in the frontline group, the 1-year and 2-year EFS and OS rates were all 93%.

For the relapsed/refractory cohort, the estimated 2-year EFS was 41% and OS was 53%. For the CML cohort, the 2-year EFS was 60%, with all patients still alive at last follow-up.

There were no grade 4 adverse events on study. Grade 3 adverse events considered at least possibly related to study treatment were elevated lipase, fever/febrile neutropenia, increased alanine aminotransferase, cerebrovascular ischemia, hypertension, pancreatitis, deep vein thrombosis, and encephalopathy. There were no cases of grade 3 cytokine release syndrome or tremor.

The study was sponsored by MD Anderson Cancer Center with collaboration from the National Cancer Institute, Amgen, and Takeda. Dr. Short has disclosed relationships with Amgen and Takeda. Dr. Nichols reported having no conflicts of interest.

For adults with Philadelphia chromosome–positive acute lymphoblastic leukemia (Ph+ALL), frontline therapy with the chemotherapy-free combination of ponatinib (Iclusig) and blinatumomab (Blincyto) shows promise as an alternative to early hematopoietic stem cell transplantation (HSCT), investigators in a single-arm phase 2 study reported.

In an interim analysis of the combination in patients with newly diagnosed or relapsed/refractory Ph+ALL or lymphoid accelerated or blast phase chronic myeloid leukemia (CML), 20 patients who received it as frontline therapy had a rate of complete responses (CR) or complete responses with partial recovery of blood counts (CRp) of 100% and a complete molecular remission (CMR) rate of 85%, reported Nicholas Short, MD, of the University of Texas MD Anderson Cancer Center in Houston.

“This translated into an estimated 2-year overall survival of 93%, with no patients undergoing transplant in first remission, and none having relapse at last follow-up,” he said in an oral abstract presented during the European Hematology Association annual congress.

Among patients with relapsed/refractory Ph+ALL, the CR/CRp rate was 89%, the CMR rate was 88%, and the estimated 2-year overall survival rate was 53%, he said.
 

Transplants on hold

“The big selling point is the ability to avoid stem cell transplant, which is not always the first thing you do in Ph-positive ALL, but it’s always on your mind,” said Gwen Nichols, MD, chief medical officer of the Leukemia and Lymphoma Society, who was not involved in the study.

“It looks, albeit with very limited follow-up, that patients haven’t relapsed yet such that transplant would be necessary. Anything we can do to avoid people having long-term complications that go along with an allogeneic transplant is a step in the right direction,” she said in an interview.
 

One combination, three cohorts

Ph+ALL comprises about 25% of all adult ALL. The standard of care in newly diagnosed patients is chemotherapy plus a tyrosine kinase inhibitor (TKI) targeted against the BCR-ABL transcript.

Ponatinib is a pan-BCR-ABL TKI that has been shown to have activity against ALL with T315I mutations, which are present in about 75% of the cases of relapsed disease, Dr. Short said.

Blinatumomab is a bi-specific T-cell engager (BiTe) that has been shown to be effective as monotherapy against relapsed/refractory Ph+ALL as monotherapy and in combination with dasatinib.

Dr. Short and colleagues enrolled patients with newly diagnosed or relapsed/refractory Ph+ALL or lymphoid accelerated or blast phase CML. Patients in the frontline cohort could have received one or two prior lines of chemotherapy with or without a TKI.

The patients all had Eastern Cooperative Oncology Group performance status of 0-2, and adequate liver function.

Patients with clinically significant cardiovascular disease or central nervous system disease pathology were excluded, except that patients with CNS leukemia could be enrolled.

The induction phase consisted of 30 mg ponatinib daily plus blinatumomab standard dosing on a 4-week-on, 2-week-off schedule. Patients in CMR, defined for frontline patients as undetectable BCR-ABL transcripts by polymerase chain reaction, then received up to four consolidation cycles of the regimen with ponatinib at a 15-mg dose, followed by 5 years of ponatinib 15-mg maintenance. All patients also received CNS prophylaxis with 12 cycles of intrathecal chemotherapy with alternating administration of methotrexate and cytarabine.

Of the 35 patients treated to date with the combination, 20 with Ph+ALL received it as frontline therapy and 10 received it for relapsed/refractory disease; 5 patients with CML in lymphoid blast phase also were treated.
 

High CMR, CR rates

As noted before, the CMR rate, the primary endpoint among patients with newly diagnosed Ph+ALL, was 85%, with a CR/CRp rate of 100%. Six of the patients in the frontline group and one in the salvage therapy group had CRs but were positive for minimal residual disease (MRD) at study outset.

The CR/CRp rate for the entire cohort of 28 patients (excluding those with a CR at start) was 96%, with only 1 patient who had relapsed/refractory disease not having a CR. This patient had received ponatinib in a prior salvage regimen.

The CMR rate among the entire cohort was 79%, with 85% of patients in the frontline ALL cohort having a CMR, 88% in the relapsed/refractory cohort, and 40% in the CML cohort. There were no early deaths among any patients.

“After one cycle of ponatinib plus blinatumomab, 84% of frontline patients had achieved at least a major molecular response, and 58% had achieved a CMR. Among those with relapsed/refractory Ph+ALL, 75% achieved CMR after one cycle of therapy,” Dr. Short said.

Of the 20 frontline patients in CR, one patient experienced visual changes and possible stroke that were considered possibly related to the study medication. This patient was taken off study. During a later maintenance regimen this patient developed a non-ST elevation myocardial infarction and died from postprocedural bleeding and hypovolemic shock following a cardiac catheterization procedure.

The remainder of patients in the frontline cohort had ongoing responses without the need for HSCT at last follow-up. There were no relapses, with a median duration of CR of 6 months,

Among the 10 with relapsed/refractory Ph+ALL, one did not have a response, and the remaining 9 had CR/CRps.

Of the latter groups, four went on to allogeneic HSCT and three were still alive; one patient who underwent a transplant experienced a relapse and died. One additional patient was alive with relapsed disease with T315I and E255V mutations at the time of relapse, one patient in CR who went off study due to insurance issues died from an unknown cause, and the three remaining patients had ongoing responses without transplant.

Among the five patients with CML in lymphoid blast phase, two had relapses, but both are still alive and currently in remission, and three have ongoing responses without transplant.

After a median follow-up of 12 months the 1-year event-free survival (EFS) rate for the entire 35-patient group was 76%, and the 2-year EFS was 70%.

The 1-year overall survival rate was 93%, and the 2-year OS rate was 80%.

Among patients in the frontline group, the 1-year and 2-year EFS and OS rates were all 93%.

For the relapsed/refractory cohort, the estimated 2-year EFS was 41% and OS was 53%. For the CML cohort, the 2-year EFS was 60%, with all patients still alive at last follow-up.

There were no grade 4 adverse events on study. Grade 3 adverse events considered at least possibly related to study treatment were elevated lipase, fever/febrile neutropenia, increased alanine aminotransferase, cerebrovascular ischemia, hypertension, pancreatitis, deep vein thrombosis, and encephalopathy. There were no cases of grade 3 cytokine release syndrome or tremor.

The study was sponsored by MD Anderson Cancer Center with collaboration from the National Cancer Institute, Amgen, and Takeda. Dr. Short has disclosed relationships with Amgen and Takeda. Dr. Nichols reported having no conflicts of interest.

In May 2020, two major scientific journals published and subsequently retracted studies that relied on data provided by the now-disgraced data analytics company Surgisphere.

One of the studies, published in The Lancet, reported an association between the antimalarial drugs hydroxychloroquine and chloroquine and increased in-hospital mortality and cardiac arrhythmias in patients with COVID-19. The second study, which appeared in the New England Journal of Medicine, described an association between underlying cardiovascular disease, but not related drug therapy, with increased mortality in COVID-19 patients.

The retractions in June 2020 followed an open letter to each publication penned by scientists, ethicists, and clinicians who flagged serious methodological and ethical anomalies in the data used in the studies.

On the 1-year anniversary, researchers and journal editors spoke about what was learned to reduce the risk of something like this happening again.

“The Surgisphere incident served as a wake-up call for everyone involved with scientific research to make sure that data have integrity and are robust,” Sunil Rao, MD, professor of medicine, Duke University Health System, Durham, N.C., and editor-in-chief of Circulation: Cardiovascular Interventions, said in an interview.

“I’m sure this isn’t going to be the last incident of this nature, and we have to be vigilant about new datasets or datasets that we haven’t heard of as having a track record of publication,” Dr. Rao said.
 

Spotlight on authors

The editors of the Lancet Group responded to the “wake-up call” with a statement, Learning From a Retraction, which announced changes to reduce the risks of research and publication misconduct.

The changes affect multiple phases of the publication process. For example, the declaration form that authors must sign “will require that more than one author has directly accessed and verified the data reported in the manuscript.” Additionally, when a research article is the result of an academic and commercial partnership – as was the case in the two retracted studies – “one of the authors named as having accessed and verified data must be from the academic team.”

This was particularly important because it appears that the academic coauthors of the retracted studies did not have access to the data provided by Surgisphere, a private commercial entity.

Mandeep R. Mehra, MD, William Harvey Distinguished Chair in Advanced Cardiovascular Medicine, Brigham and Women’s Hospital, Boston, who was the lead author of both studies, declined to be interviewed for this article. In a letter to the New England Journal of Medicine editors requesting that the article be retracted, he wrote: “Because all the authors were not granted access to the raw data and the raw data could not be made available to a third-party auditor, we are unable to validate the primary data sources underlying our article.”

In a similar communication with The Lancet, Dr. Mehra wrote even more pointedly that, in light of the refusal of Surgisphere to make the data available to the third-party auditor, “we can no longer vouch for the veracity of the primary data sources.”

“It is very disturbing that the authors were willing to put their names on a paper without ever seeing and verifying the data,” Mario Malički, MD, PhD, a postdoctoral researcher at METRICS at Stanford (Calif.) University, said in an interview. “Saying that they could ‘no longer vouch’ suggests that at one point they could vouch for it. Most likely they took its existence and veracity entirely on trust.”

Dr. Malički pointed out that one of the four criteria of the International Committee of Medical Journal Editors for being an author on a study is the “agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.”

The new policies put forth by The Lancet are “encouraging,” but perhaps do not go far enough. “Every author, not only one or two authors, should personally take responsibility for the integrity of data,” he stated.

Many journals “adhere to ICMJE rules in principle and have checkboxes for authors to confirm that they guarantee the veracity of the data.” However, they “do not have the resources to verify the authors’ statements.”

Ideally, “it is the institutions where the researchers work that should guarantee the veracity of the raw data – but I do not know any university or institute that does this,” he said.
 

No ‘good-housekeeping’ seal

For articles based on large, real-world datasets, the Lancet Group will now require that editors ensure that at least one peer reviewer is “knowledgeable about the details of the dataset being reported and can understand its strengths and limitations in relation to the question being addressed.”

For studies that use “very large datasets,” the editors are now required to ensure that, in addition to a statistical peer review, a review from an “expert in data science” is obtained. Reviewers will also be explicitly asked if they have “concerns about research integrity or publication ethics regarding the manuscript they are reviewing.”

Although these changes are encouraging, Harlan Krumholz, MD, professor of medicine (cardiology), Yale University, New Haven, Conn., is not convinced that they are realistic.

Dr. Krumholz, who is also the founder and director of the Yale New Haven Hospital Center for Outcome Research and Evaluation, said in an interview that “large, real-world datasets” are of two varieties. Datasets drawn from publicly available sources, such as Medicare or Medicaid health records, are utterly transparent.

By contrast, Surgisphere was a privately owned database, and “it is not unusual for privately owned databases to have proprietary data from multiple sources that the company may choose to keep confidential,” Dr. Krumholz said.

He noted that several large datasets are widely used for research purposes, such as IBM, Optum, and Komodo – a data analytics company that recently entered into partnership with a fourth company, PicnicHealth.

These companies receive deidentified electronic health records from health systems and insurers nationwide. Komodo boasts “real-time and longitudinal data on more than 325 million patients, representing more than 65 billion clinical encounters with 15 million new encounters added daily.”

“One has to raise an eyebrow – how were these data acquired? And, given that the U.S. has a population of around 328 million people, is it really plausible that a single company has health records of almost the entire U.S. population?” Dr. Krumholz commented. (A spokesperson for Komodo said in an interview that the company has records on 325 million U.S. patients.)

This is “an issue across the board with ‘real-world evidence,’ which is that it’s like the ‘Wild West’ – the transparencies of private databases are less than optimal and there are no common standards to help us move forward,” Dr. Krumholz said, noting that there is “no external authority overseeing, validating, or auditing these databases. In the end, we are trusting the companies.”

Although the Food and Drug Administration has laid out a framework for how real-world data and real-world evidence can be used to advance scientific research, the FDA does not oversee the databases.

“Thus, there is no ‘good housekeeping seal’ that a peer reviewer or author would be in a position to evaluate,” Dr. Krumholz said. “No journal can do an audit of these types of private databases, so ultimately, it boils down to trust.”

Nevertheless, there were red flags with Surgisphere, Dr. Rao pointed out. Unlike more established and widely used databases, the Surgisphere database had been catapulted from relative obscurity onto center stage, which should have given researchers pause.
 

AI-assisted peer review

A series of investigative reports by The Guardian raised questions about Sapan Desai, the CEO of Surgisphere, including the fact that hospitals purporting to have contributed data to Surgisphere had never heard of the company.

However, peer reviewers are not expected to be investigative reporters, explained Dr. Malički.

“In an ideal world, editors and peer reviewers would have a chance to look at raw data or would have a certificate from the academic institution the authors are affiliated with that the data have been inspected by the institution, but in the real world, of course, this does not happen,” he said.

Artificial intelligence software is being developed and deployed to assist in the peer review process, Dr. Malički noted. In July 2020, Frontiers Science News debuted its Artificial Intelligence Review Assistant to help editors, reviewers, and authors evaluate the quality of a manuscript. The program can make up to 20 recommendations, including “the assessment of language quality, the detection of plagiarism, and identification of potential conflicts of interest.” The program is now in use in all 103 journals published by Frontiers. Preliminary software is also available to detect statistical errors.

Another system under development is FAIRware, an initiative of the Research on Research Institute in partnership with the Stanford Center for Biomedical Informatics Research. The partnership’s goal is to “develop an automated online tool (or suite of tools) to help researchers ensure that the datasets they produce are ‘FAIR’ at the point of creation,” said Dr. Malički, referring to the findability, accessibility, interoperability, and reusability (FAIR) guiding principles for data management. The principles aim to increase the ability of machines to automatically find and use the data, as well as to support its reuse by individuals.

He added that these advanced tools cannot replace human reviewers, who will “likely always be a necessary quality check in the process.”
 

Greater transparency needed

Another limitation of peer review is the reviewers themselves, according to Dr. Malički. “It’s a step in the right direction that The Lancet is now requesting a peer reviewer with expertise in big datasets, but it does not go far enough to increase accountability of peer reviewers,” he said.

Dr. Malički is the co–editor-in-chief of the journal Research Integrity and Peer Review , which has “an open and transparent review process – meaning that we reveal the names of the reviewers to the public and we publish the full review report alongside the paper.” The publication also allows the authors to make public the original version they sent.

Dr. Malički cited several advantages to transparent peer review, particularly the increased accountability that results from placing potential conflicts of interest under the microscope.

As for the concern that identifying the reviewers might soften the review process, “there is little evidence to substantiate that concern,” he added.

Dr. Malički emphasized that making reviews public “is not a problem – people voice strong opinions at conferences and elsewhere. The question remains, who gets to decide if the criticism has been adequately addressed, so that the findings of the study still stand?”

He acknowledged that, “as in politics and on many social platforms, rage, hatred, and personal attacks divert the discussion from the topic at hand, which is why a good moderator is needed.”

A journal editor or a moderator at a scientific conference may be tasked with “stopping all talk not directly related to the topic.”
 

Widening the circle of scrutiny

Dr. Malički added: “A published paper should not be considered the ‘final word,’ even if it has gone through peer review and is published in a reputable journal. The peer-review process means that a limited number of people have seen the study.”

Once the study is published, “the whole world gets to see it and criticize it, and that widens the circle of scrutiny.”

One classic way to raise concerns about a study post publication is to write a letter to the journal editor. But there is no guarantee that the letter will be published or the authors notified of the feedback.

Dr. Malički encourages readers to use PubPeer, an online forum in which members of the public can post comments on scientific studies and articles.

Once a comment is posted, the authors are alerted. “There is no ‘police department’ that forces authors to acknowledge comments or forces journal editors to take action, but at least PubPeer guarantees that readers’ messages will reach the authors and – depending on how many people raise similar issues – the comments can lead to errata or even full retractions,” he said.

PubPeer was key in pointing out errors in a suspect study from France (which did not involve Surgisphere) that supported the use of hydroxychloroquine in COVID-19.
 

A message to policy makers

High stakes are involved in ensuring the integrity of scientific publications: The French government revoked a decree that allowed hospitals to prescribe hydroxychloroquine for certain COVID-19 patients.

After the Surgisphere Lancet article, the World Health Organization temporarily halted enrollment in the hydroxychloroquine component of the Solidarity international randomized trial of medications to treat COVID-19.

Similarly, the U.K. Medicines and Healthcare Products Regulatory Agency instructed the organizers of COPCOV, an international trial of the use of hydroxychloroquine as prophylaxis against COVID-19, to suspend recruitment of patients. The SOLIDARITY trial briefly resumed, but that arm of the trial was ultimately suspended after a preliminary analysis suggested that hydroxychloroquine provided no benefit for patients with COVID-19.

Dr. Malički emphasized that governments and organizations should not “blindly trust journal articles” and make policy decisions based exclusively on study findings in published journals – even with the current improvements in the peer review process – without having their own experts conduct a thorough review of the data.

“If you are not willing to do your own due diligence, then at least be brave enough and say transparently why you are making this policy, or any other changes, and clearly state if your decision is based primarily or solely on the fact that ‘X’ study was published in ‘Y’ journal,” he stated.

Dr. Rao believes that the most important take-home message of the Surgisphere scandal is “that we should be skeptical and do our own due diligence about the kinds of data published – a responsibility that applies to all of us, whether we are investigators, editors at journals, the press, scientists, and readers.”

Dr. Rao reported being on the steering committee of the National Heart, Lung, and Blood Institute–sponsored MINT trial and the Bayer-sponsored PACIFIC AMI trial. Dr. Malički reports being a postdoc at METRICS Stanford in the past 3 years. Dr. Krumholz received expenses and/or personal fees from UnitedHealth, Element Science, Aetna, Facebook, the Siegfried and Jensen Law Firm, Arnold and Porter Law Firm, Martin/Baughman Law Firm, F-Prime, and the National Center for Cardiovascular Diseases in Beijing. He is an owner of Refactor Health and HugoHealth and had grants and/or contracts from the Centers for Medicare & Medicaid Services, the FDA, Johnson & Johnson, and the Shenzhen Center for Health Information.

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

In May 2020, two major scientific journals published and subsequently retracted studies that relied on data provided by the now-disgraced data analytics company Surgisphere.

One of the studies, published in The Lancet, reported an association between the antimalarial drugs hydroxychloroquine and chloroquine and increased in-hospital mortality and cardiac arrhythmias in patients with COVID-19. The second study, which appeared in the New England Journal of Medicine, described an association between underlying cardiovascular disease, but not related drug therapy, with increased mortality in COVID-19 patients.

The retractions in June 2020 followed an open letter to each publication penned by scientists, ethicists, and clinicians who flagged serious methodological and ethical anomalies in the data used in the studies.

On the 1-year anniversary, researchers and journal editors spoke about what was learned to reduce the risk of something like this happening again.

“The Surgisphere incident served as a wake-up call for everyone involved with scientific research to make sure that data have integrity and are robust,” Sunil Rao, MD, professor of medicine, Duke University Health System, Durham, N.C., and editor-in-chief of Circulation: Cardiovascular Interventions, said in an interview.

“I’m sure this isn’t going to be the last incident of this nature, and we have to be vigilant about new datasets or datasets that we haven’t heard of as having a track record of publication,” Dr. Rao said.
 

Spotlight on authors

The editors of the Lancet Group responded to the “wake-up call” with a statement, Learning From a Retraction, which announced changes to reduce the risks of research and publication misconduct.

The changes affect multiple phases of the publication process. For example, the declaration form that authors must sign “will require that more than one author has directly accessed and verified the data reported in the manuscript.” Additionally, when a research article is the result of an academic and commercial partnership – as was the case in the two retracted studies – “one of the authors named as having accessed and verified data must be from the academic team.”

This was particularly important because it appears that the academic coauthors of the retracted studies did not have access to the data provided by Surgisphere, a private commercial entity.

Mandeep R. Mehra, MD, William Harvey Distinguished Chair in Advanced Cardiovascular Medicine, Brigham and Women’s Hospital, Boston, who was the lead author of both studies, declined to be interviewed for this article. In a letter to the New England Journal of Medicine editors requesting that the article be retracted, he wrote: “Because all the authors were not granted access to the raw data and the raw data could not be made available to a third-party auditor, we are unable to validate the primary data sources underlying our article.”

In a similar communication with The Lancet, Dr. Mehra wrote even more pointedly that, in light of the refusal of Surgisphere to make the data available to the third-party auditor, “we can no longer vouch for the veracity of the primary data sources.”

“It is very disturbing that the authors were willing to put their names on a paper without ever seeing and verifying the data,” Mario Malički, MD, PhD, a postdoctoral researcher at METRICS at Stanford (Calif.) University, said in an interview. “Saying that they could ‘no longer vouch’ suggests that at one point they could vouch for it. Most likely they took its existence and veracity entirely on trust.”

Dr. Malički pointed out that one of the four criteria of the International Committee of Medical Journal Editors for being an author on a study is the “agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.”

The new policies put forth by The Lancet are “encouraging,” but perhaps do not go far enough. “Every author, not only one or two authors, should personally take responsibility for the integrity of data,” he stated.

Many journals “adhere to ICMJE rules in principle and have checkboxes for authors to confirm that they guarantee the veracity of the data.” However, they “do not have the resources to verify the authors’ statements.”

Ideally, “it is the institutions where the researchers work that should guarantee the veracity of the raw data – but I do not know any university or institute that does this,” he said.
 

No ‘good-housekeeping’ seal

For articles based on large, real-world datasets, the Lancet Group will now require that editors ensure that at least one peer reviewer is “knowledgeable about the details of the dataset being reported and can understand its strengths and limitations in relation to the question being addressed.”

For studies that use “very large datasets,” the editors are now required to ensure that, in addition to a statistical peer review, a review from an “expert in data science” is obtained. Reviewers will also be explicitly asked if they have “concerns about research integrity or publication ethics regarding the manuscript they are reviewing.”

Although these changes are encouraging, Harlan Krumholz, MD, professor of medicine (cardiology), Yale University, New Haven, Conn., is not convinced that they are realistic.

Dr. Krumholz, who is also the founder and director of the Yale New Haven Hospital Center for Outcome Research and Evaluation, said in an interview that “large, real-world datasets” are of two varieties. Datasets drawn from publicly available sources, such as Medicare or Medicaid health records, are utterly transparent.

By contrast, Surgisphere was a privately owned database, and “it is not unusual for privately owned databases to have proprietary data from multiple sources that the company may choose to keep confidential,” Dr. Krumholz said.

He noted that several large datasets are widely used for research purposes, such as IBM, Optum, and Komodo – a data analytics company that recently entered into partnership with a fourth company, PicnicHealth.

These companies receive deidentified electronic health records from health systems and insurers nationwide. Komodo boasts “real-time and longitudinal data on more than 325 million patients, representing more than 65 billion clinical encounters with 15 million new encounters added daily.”

“One has to raise an eyebrow – how were these data acquired? And, given that the U.S. has a population of around 328 million people, is it really plausible that a single company has health records of almost the entire U.S. population?” Dr. Krumholz commented. (A spokesperson for Komodo said in an interview that the company has records on 325 million U.S. patients.)

This is “an issue across the board with ‘real-world evidence,’ which is that it’s like the ‘Wild West’ – the transparencies of private databases are less than optimal and there are no common standards to help us move forward,” Dr. Krumholz said, noting that there is “no external authority overseeing, validating, or auditing these databases. In the end, we are trusting the companies.”

Although the Food and Drug Administration has laid out a framework for how real-world data and real-world evidence can be used to advance scientific research, the FDA does not oversee the databases.

“Thus, there is no ‘good housekeeping seal’ that a peer reviewer or author would be in a position to evaluate,” Dr. Krumholz said. “No journal can do an audit of these types of private databases, so ultimately, it boils down to trust.”

Nevertheless, there were red flags with Surgisphere, Dr. Rao pointed out. Unlike more established and widely used databases, the Surgisphere database had been catapulted from relative obscurity onto center stage, which should have given researchers pause.
 

AI-assisted peer review

A series of investigative reports by The Guardian raised questions about Sapan Desai, the CEO of Surgisphere, including the fact that hospitals purporting to have contributed data to Surgisphere had never heard of the company.

However, peer reviewers are not expected to be investigative reporters, explained Dr. Malički.

“In an ideal world, editors and peer reviewers would have a chance to look at raw data or would have a certificate from the academic institution the authors are affiliated with that the data have been inspected by the institution, but in the real world, of course, this does not happen,” he said.

Artificial intelligence software is being developed and deployed to assist in the peer review process, Dr. Malički noted. In July 2020, Frontiers Science News debuted its Artificial Intelligence Review Assistant to help editors, reviewers, and authors evaluate the quality of a manuscript. The program can make up to 20 recommendations, including “the assessment of language quality, the detection of plagiarism, and identification of potential conflicts of interest.” The program is now in use in all 103 journals published by Frontiers. Preliminary software is also available to detect statistical errors.

Another system under development is FAIRware, an initiative of the Research on Research Institute in partnership with the Stanford Center for Biomedical Informatics Research. The partnership’s goal is to “develop an automated online tool (or suite of tools) to help researchers ensure that the datasets they produce are ‘FAIR’ at the point of creation,” said Dr. Malički, referring to the findability, accessibility, interoperability, and reusability (FAIR) guiding principles for data management. The principles aim to increase the ability of machines to automatically find and use the data, as well as to support its reuse by individuals.

He added that these advanced tools cannot replace human reviewers, who will “likely always be a necessary quality check in the process.”
 

Greater transparency needed

Another limitation of peer review is the reviewers themselves, according to Dr. Malički. “It’s a step in the right direction that The Lancet is now requesting a peer reviewer with expertise in big datasets, but it does not go far enough to increase accountability of peer reviewers,” he said.

Dr. Malički is the co–editor-in-chief of the journal Research Integrity and Peer Review , which has “an open and transparent review process – meaning that we reveal the names of the reviewers to the public and we publish the full review report alongside the paper.” The publication also allows the authors to make public the original version they sent.

Dr. Malički cited several advantages to transparent peer review, particularly the increased accountability that results from placing potential conflicts of interest under the microscope.

As for the concern that identifying the reviewers might soften the review process, “there is little evidence to substantiate that concern,” he added.

Dr. Malički emphasized that making reviews public “is not a problem – people voice strong opinions at conferences and elsewhere. The question remains, who gets to decide if the criticism has been adequately addressed, so that the findings of the study still stand?”

He acknowledged that, “as in politics and on many social platforms, rage, hatred, and personal attacks divert the discussion from the topic at hand, which is why a good moderator is needed.”

A journal editor or a moderator at a scientific conference may be tasked with “stopping all talk not directly related to the topic.”
 

Widening the circle of scrutiny

Dr. Malički added: “A published paper should not be considered the ‘final word,’ even if it has gone through peer review and is published in a reputable journal. The peer-review process means that a limited number of people have seen the study.”

Once the study is published, “the whole world gets to see it and criticize it, and that widens the circle of scrutiny.”

One classic way to raise concerns about a study post publication is to write a letter to the journal editor. But there is no guarantee that the letter will be published or the authors notified of the feedback.

Dr. Malički encourages readers to use PubPeer, an online forum in which members of the public can post comments on scientific studies and articles.

Once a comment is posted, the authors are alerted. “There is no ‘police department’ that forces authors to acknowledge comments or forces journal editors to take action, but at least PubPeer guarantees that readers’ messages will reach the authors and – depending on how many people raise similar issues – the comments can lead to errata or even full retractions,” he said.

PubPeer was key in pointing out errors in a suspect study from France (which did not involve Surgisphere) that supported the use of hydroxychloroquine in COVID-19.
 

A message to policy makers

High stakes are involved in ensuring the integrity of scientific publications: The French government revoked a decree that allowed hospitals to prescribe hydroxychloroquine for certain COVID-19 patients.

After the Surgisphere Lancet article, the World Health Organization temporarily halted enrollment in the hydroxychloroquine component of the Solidarity international randomized trial of medications to treat COVID-19.

Similarly, the U.K. Medicines and Healthcare Products Regulatory Agency instructed the organizers of COPCOV, an international trial of the use of hydroxychloroquine as prophylaxis against COVID-19, to suspend recruitment of patients. The SOLIDARITY trial briefly resumed, but that arm of the trial was ultimately suspended after a preliminary analysis suggested that hydroxychloroquine provided no benefit for patients with COVID-19.

Dr. Malički emphasized that governments and organizations should not “blindly trust journal articles” and make policy decisions based exclusively on study findings in published journals – even with the current improvements in the peer review process – without having their own experts conduct a thorough review of the data.

“If you are not willing to do your own due diligence, then at least be brave enough and say transparently why you are making this policy, or any other changes, and clearly state if your decision is based primarily or solely on the fact that ‘X’ study was published in ‘Y’ journal,” he stated.

Dr. Rao believes that the most important take-home message of the Surgisphere scandal is “that we should be skeptical and do our own due diligence about the kinds of data published – a responsibility that applies to all of us, whether we are investigators, editors at journals, the press, scientists, and readers.”

Dr. Rao reported being on the steering committee of the National Heart, Lung, and Blood Institute–sponsored MINT trial and the Bayer-sponsored PACIFIC AMI trial. Dr. Malički reports being a postdoc at METRICS Stanford in the past 3 years. Dr. Krumholz received expenses and/or personal fees from UnitedHealth, Element Science, Aetna, Facebook, the Siegfried and Jensen Law Firm, Arnold and Porter Law Firm, Martin/Baughman Law Firm, F-Prime, and the National Center for Cardiovascular Diseases in Beijing. He is an owner of Refactor Health and HugoHealth and had grants and/or contracts from the Centers for Medicare & Medicaid Services, the FDA, Johnson & Johnson, and the Shenzhen Center for Health Information.

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

In May 2020, two major scientific journals published and subsequently retracted studies that relied on data provided by the now-disgraced data analytics company Surgisphere.

One of the studies, published in The Lancet, reported an association between the antimalarial drugs hydroxychloroquine and chloroquine and increased in-hospital mortality and cardiac arrhythmias in patients with COVID-19. The second study, which appeared in the New England Journal of Medicine, described an association between underlying cardiovascular disease, but not related drug therapy, with increased mortality in COVID-19 patients.

The retractions in June 2020 followed an open letter to each publication penned by scientists, ethicists, and clinicians who flagged serious methodological and ethical anomalies in the data used in the studies.

On the 1-year anniversary, researchers and journal editors spoke about what was learned to reduce the risk of something like this happening again.

“The Surgisphere incident served as a wake-up call for everyone involved with scientific research to make sure that data have integrity and are robust,” Sunil Rao, MD, professor of medicine, Duke University Health System, Durham, N.C., and editor-in-chief of Circulation: Cardiovascular Interventions, said in an interview.

“I’m sure this isn’t going to be the last incident of this nature, and we have to be vigilant about new datasets or datasets that we haven’t heard of as having a track record of publication,” Dr. Rao said.
 

Spotlight on authors

The editors of the Lancet Group responded to the “wake-up call” with a statement, Learning From a Retraction, which announced changes to reduce the risks of research and publication misconduct.

The changes affect multiple phases of the publication process. For example, the declaration form that authors must sign “will require that more than one author has directly accessed and verified the data reported in the manuscript.” Additionally, when a research article is the result of an academic and commercial partnership – as was the case in the two retracted studies – “one of the authors named as having accessed and verified data must be from the academic team.”

This was particularly important because it appears that the academic coauthors of the retracted studies did not have access to the data provided by Surgisphere, a private commercial entity.

Mandeep R. Mehra, MD, William Harvey Distinguished Chair in Advanced Cardiovascular Medicine, Brigham and Women’s Hospital, Boston, who was the lead author of both studies, declined to be interviewed for this article. In a letter to the New England Journal of Medicine editors requesting that the article be retracted, he wrote: “Because all the authors were not granted access to the raw data and the raw data could not be made available to a third-party auditor, we are unable to validate the primary data sources underlying our article.”

In a similar communication with The Lancet, Dr. Mehra wrote even more pointedly that, in light of the refusal of Surgisphere to make the data available to the third-party auditor, “we can no longer vouch for the veracity of the primary data sources.”

“It is very disturbing that the authors were willing to put their names on a paper without ever seeing and verifying the data,” Mario Malički, MD, PhD, a postdoctoral researcher at METRICS at Stanford (Calif.) University, said in an interview. “Saying that they could ‘no longer vouch’ suggests that at one point they could vouch for it. Most likely they took its existence and veracity entirely on trust.”

Dr. Malički pointed out that one of the four criteria of the International Committee of Medical Journal Editors for being an author on a study is the “agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.”

The new policies put forth by The Lancet are “encouraging,” but perhaps do not go far enough. “Every author, not only one or two authors, should personally take responsibility for the integrity of data,” he stated.

Many journals “adhere to ICMJE rules in principle and have checkboxes for authors to confirm that they guarantee the veracity of the data.” However, they “do not have the resources to verify the authors’ statements.”

Ideally, “it is the institutions where the researchers work that should guarantee the veracity of the raw data – but I do not know any university or institute that does this,” he said.
 

No ‘good-housekeeping’ seal

For articles based on large, real-world datasets, the Lancet Group will now require that editors ensure that at least one peer reviewer is “knowledgeable about the details of the dataset being reported and can understand its strengths and limitations in relation to the question being addressed.”

For studies that use “very large datasets,” the editors are now required to ensure that, in addition to a statistical peer review, a review from an “expert in data science” is obtained. Reviewers will also be explicitly asked if they have “concerns about research integrity or publication ethics regarding the manuscript they are reviewing.”

Although these changes are encouraging, Harlan Krumholz, MD, professor of medicine (cardiology), Yale University, New Haven, Conn., is not convinced that they are realistic.

Dr. Krumholz, who is also the founder and director of the Yale New Haven Hospital Center for Outcome Research and Evaluation, said in an interview that “large, real-world datasets” are of two varieties. Datasets drawn from publicly available sources, such as Medicare or Medicaid health records, are utterly transparent.

By contrast, Surgisphere was a privately owned database, and “it is not unusual for privately owned databases to have proprietary data from multiple sources that the company may choose to keep confidential,” Dr. Krumholz said.

He noted that several large datasets are widely used for research purposes, such as IBM, Optum, and Komodo – a data analytics company that recently entered into partnership with a fourth company, PicnicHealth.

These companies receive deidentified electronic health records from health systems and insurers nationwide. Komodo boasts “real-time and longitudinal data on more than 325 million patients, representing more than 65 billion clinical encounters with 15 million new encounters added daily.”

“One has to raise an eyebrow – how were these data acquired? And, given that the U.S. has a population of around 328 million people, is it really plausible that a single company has health records of almost the entire U.S. population?” Dr. Krumholz commented. (A spokesperson for Komodo said in an interview that the company has records on 325 million U.S. patients.)

This is “an issue across the board with ‘real-world evidence,’ which is that it’s like the ‘Wild West’ – the transparencies of private databases are less than optimal and there are no common standards to help us move forward,” Dr. Krumholz said, noting that there is “no external authority overseeing, validating, or auditing these databases. In the end, we are trusting the companies.”

Although the Food and Drug Administration has laid out a framework for how real-world data and real-world evidence can be used to advance scientific research, the FDA does not oversee the databases.

“Thus, there is no ‘good housekeeping seal’ that a peer reviewer or author would be in a position to evaluate,” Dr. Krumholz said. “No journal can do an audit of these types of private databases, so ultimately, it boils down to trust.”

Nevertheless, there were red flags with Surgisphere, Dr. Rao pointed out. Unlike more established and widely used databases, the Surgisphere database had been catapulted from relative obscurity onto center stage, which should have given researchers pause.
 

AI-assisted peer review

A series of investigative reports by The Guardian raised questions about Sapan Desai, the CEO of Surgisphere, including the fact that hospitals purporting to have contributed data to Surgisphere had never heard of the company.

However, peer reviewers are not expected to be investigative reporters, explained Dr. Malički.

“In an ideal world, editors and peer reviewers would have a chance to look at raw data or would have a certificate from the academic institution the authors are affiliated with that the data have been inspected by the institution, but in the real world, of course, this does not happen,” he said.

Artificial intelligence software is being developed and deployed to assist in the peer review process, Dr. Malički noted. In July 2020, Frontiers Science News debuted its Artificial Intelligence Review Assistant to help editors, reviewers, and authors evaluate the quality of a manuscript. The program can make up to 20 recommendations, including “the assessment of language quality, the detection of plagiarism, and identification of potential conflicts of interest.” The program is now in use in all 103 journals published by Frontiers. Preliminary software is also available to detect statistical errors.

Another system under development is FAIRware, an initiative of the Research on Research Institute in partnership with the Stanford Center for Biomedical Informatics Research. The partnership’s goal is to “develop an automated online tool (or suite of tools) to help researchers ensure that the datasets they produce are ‘FAIR’ at the point of creation,” said Dr. Malički, referring to the findability, accessibility, interoperability, and reusability (FAIR) guiding principles for data management. The principles aim to increase the ability of machines to automatically find and use the data, as well as to support its reuse by individuals.

He added that these advanced tools cannot replace human reviewers, who will “likely always be a necessary quality check in the process.”
 

Greater transparency needed

Another limitation of peer review is the reviewers themselves, according to Dr. Malički. “It’s a step in the right direction that The Lancet is now requesting a peer reviewer with expertise in big datasets, but it does not go far enough to increase accountability of peer reviewers,” he said.

Dr. Malički is the co–editor-in-chief of the journal Research Integrity and Peer Review , which has “an open and transparent review process – meaning that we reveal the names of the reviewers to the public and we publish the full review report alongside the paper.” The publication also allows the authors to make public the original version they sent.

Dr. Malički cited several advantages to transparent peer review, particularly the increased accountability that results from placing potential conflicts of interest under the microscope.

As for the concern that identifying the reviewers might soften the review process, “there is little evidence to substantiate that concern,” he added.

Dr. Malički emphasized that making reviews public “is not a problem – people voice strong opinions at conferences and elsewhere. The question remains, who gets to decide if the criticism has been adequately addressed, so that the findings of the study still stand?”

He acknowledged that, “as in politics and on many social platforms, rage, hatred, and personal attacks divert the discussion from the topic at hand, which is why a good moderator is needed.”

A journal editor or a moderator at a scientific conference may be tasked with “stopping all talk not directly related to the topic.”
 

Widening the circle of scrutiny

Dr. Malički added: “A published paper should not be considered the ‘final word,’ even if it has gone through peer review and is published in a reputable journal. The peer-review process means that a limited number of people have seen the study.”

Once the study is published, “the whole world gets to see it and criticize it, and that widens the circle of scrutiny.”

One classic way to raise concerns about a study post publication is to write a letter to the journal editor. But there is no guarantee that the letter will be published or the authors notified of the feedback.

Dr. Malički encourages readers to use PubPeer, an online forum in which members of the public can post comments on scientific studies and articles.

Once a comment is posted, the authors are alerted. “There is no ‘police department’ that forces authors to acknowledge comments or forces journal editors to take action, but at least PubPeer guarantees that readers’ messages will reach the authors and – depending on how many people raise similar issues – the comments can lead to errata or even full retractions,” he said.

PubPeer was key in pointing out errors in a suspect study from France (which did not involve Surgisphere) that supported the use of hydroxychloroquine in COVID-19.
 

A message to policy makers

High stakes are involved in ensuring the integrity of scientific publications: The French government revoked a decree that allowed hospitals to prescribe hydroxychloroquine for certain COVID-19 patients.

After the Surgisphere Lancet article, the World Health Organization temporarily halted enrollment in the hydroxychloroquine component of the Solidarity international randomized trial of medications to treat COVID-19.

Similarly, the U.K. Medicines and Healthcare Products Regulatory Agency instructed the organizers of COPCOV, an international trial of the use of hydroxychloroquine as prophylaxis against COVID-19, to suspend recruitment of patients. The SOLIDARITY trial briefly resumed, but that arm of the trial was ultimately suspended after a preliminary analysis suggested that hydroxychloroquine provided no benefit for patients with COVID-19.

Dr. Malički emphasized that governments and organizations should not “blindly trust journal articles” and make policy decisions based exclusively on study findings in published journals – even with the current improvements in the peer review process – without having their own experts conduct a thorough review of the data.

“If you are not willing to do your own due diligence, then at least be brave enough and say transparently why you are making this policy, or any other changes, and clearly state if your decision is based primarily or solely on the fact that ‘X’ study was published in ‘Y’ journal,” he stated.

Dr. Rao believes that the most important take-home message of the Surgisphere scandal is “that we should be skeptical and do our own due diligence about the kinds of data published – a responsibility that applies to all of us, whether we are investigators, editors at journals, the press, scientists, and readers.”

Dr. Rao reported being on the steering committee of the National Heart, Lung, and Blood Institute–sponsored MINT trial and the Bayer-sponsored PACIFIC AMI trial. Dr. Malički reports being a postdoc at METRICS Stanford in the past 3 years. Dr. Krumholz received expenses and/or personal fees from UnitedHealth, Element Science, Aetna, Facebook, the Siegfried and Jensen Law Firm, Arnold and Porter Law Firm, Martin/Baughman Law Firm, F-Prime, and the National Center for Cardiovascular Diseases in Beijing. He is an owner of Refactor Health and HugoHealth and had grants and/or contracts from the Centers for Medicare & Medicaid Services, the FDA, Johnson & Johnson, and the Shenzhen Center for Health Information.

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

As doctors struggled through several surges of COVID-19 infections, most of what we learned was acquired through real-life experience. While many treatment options were promoted, most flat-out failed to be real therapeutics at all. Now that we have a safe and effective vaccine, we can prevent many infections from this virus. However, we are still left to manage the many post-COVID symptoms our patients continue to suffer with.

Symptoms following infection can last for months and range widely from “brain fog,” fatigue, dyspnea, chest pain, generalized weakness, depression, and a host of others. Patients may experience one or all of these symptoms, and there is currently no good way to predict who will go on to become a COVID “long hauler”.

Following the example of being educated by COVID as it happened, the same is true for managing post-COVID symptoms. The medical community still has a poor understanding of why some people develop it and there are few evidence-based studies to support any treatment modalities.

Earlier this month, the Centers for Disease Control and Prevention issued a set of clinical guidelines addressing treatment of post-COVID symptoms, which they define as “new, recurring, or ongoing symptoms more than 4 weeks after infection, sometimes after initial symptom recovery.” It is important to note that these symptoms can occur in any degree of sickness during the acute infection, including in those who were asymptomatic. Even the actual name of this post-COVID syndrome is still being developed, with several other names being used for it as well.

While the guidelines are quite extensive, the actual clinical recommendations are still vague. For example, it is advised to let the patient know that post-COVID symptoms are still not well understood. While it is important to be transparent with patients, this does little to reassure them. Patients look to doctors, especially their primary care physicians, to guide them on the best treatment paths. Yet, we currently have none for post-COVID syndrome.

It is also advised to treat the patients’ symptoms and help improve functioning. For many diseases, doctors like to get to the root cause of the problem. Treating a symptom often masks an underlying condition. It may make the patient feel better and improve what they are capable of doing, which is important, but it also fails to unmask the real problem. It is also important to note that symptoms can be out of proportion to clinical findings and should not be dismissed: we just don’t have the answers yet.

One helpful recommendation is having a patient keep a diary of their symptoms. This will help both the patient and doctor learn what may be triggering factors. If it is, for example, exertion that induces breathlessness, perhaps the patient can gradually increase their level of activity to minimize symptoms. Additionally, a “comprehensive rehabilitation program” is also advised and this can greatly assist addressing all the issues a patient is experiencing, physically and medically.

It is also advised that management of underlying medical conditions be optimized. While this is very important, it is not something specific to post-COVID syndrome: All patients should have their underlying medical conditions well controlled. It might be that the patient is paying more attention to their overall health, which is a good thing. However, this does not necessarily reduce the current symptoms a patient is experiencing.

The CDC makes a good attempt to offer guidance in the frustrating management of post-COVID syndrome. However, their clinical guidelines fail to offer specific management tools specific to treating post-COVID patients. The recommendations offered are more helpful to health in general. The fact that more specific recommendations are lacking is simply caused by the lack of knowledge of this condition at present. As more research is conducted and more knowledge obtained, new guidelines should become more detailed.

Dr. Girgis practices family medicine in South River, N.J., and is a clinical assistant professor of family medicine at Robert Wood Johnson Medical School, New Brunswick, N.J. You can contact her at [email protected].

As doctors struggled through several surges of COVID-19 infections, most of what we learned was acquired through real-life experience. While many treatment options were promoted, most flat-out failed to be real therapeutics at all. Now that we have a safe and effective vaccine, we can prevent many infections from this virus. However, we are still left to manage the many post-COVID symptoms our patients continue to suffer with.

Symptoms following infection can last for months and range widely from “brain fog,” fatigue, dyspnea, chest pain, generalized weakness, depression, and a host of others. Patients may experience one or all of these symptoms, and there is currently no good way to predict who will go on to become a COVID “long hauler”.

Following the example of being educated by COVID as it happened, the same is true for managing post-COVID symptoms. The medical community still has a poor understanding of why some people develop it and there are few evidence-based studies to support any treatment modalities.

Earlier this month, the Centers for Disease Control and Prevention issued a set of clinical guidelines addressing treatment of post-COVID symptoms, which they define as “new, recurring, or ongoing symptoms more than 4 weeks after infection, sometimes after initial symptom recovery.” It is important to note that these symptoms can occur in any degree of sickness during the acute infection, including in those who were asymptomatic. Even the actual name of this post-COVID syndrome is still being developed, with several other names being used for it as well.

While the guidelines are quite extensive, the actual clinical recommendations are still vague. For example, it is advised to let the patient know that post-COVID symptoms are still not well understood. While it is important to be transparent with patients, this does little to reassure them. Patients look to doctors, especially their primary care physicians, to guide them on the best treatment paths. Yet, we currently have none for post-COVID syndrome.

It is also advised to treat the patients’ symptoms and help improve functioning. For many diseases, doctors like to get to the root cause of the problem. Treating a symptom often masks an underlying condition. It may make the patient feel better and improve what they are capable of doing, which is important, but it also fails to unmask the real problem. It is also important to note that symptoms can be out of proportion to clinical findings and should not be dismissed: we just don’t have the answers yet.

One helpful recommendation is having a patient keep a diary of their symptoms. This will help both the patient and doctor learn what may be triggering factors. If it is, for example, exertion that induces breathlessness, perhaps the patient can gradually increase their level of activity to minimize symptoms. Additionally, a “comprehensive rehabilitation program” is also advised and this can greatly assist addressing all the issues a patient is experiencing, physically and medically.

It is also advised that management of underlying medical conditions be optimized. While this is very important, it is not something specific to post-COVID syndrome: All patients should have their underlying medical conditions well controlled. It might be that the patient is paying more attention to their overall health, which is a good thing. However, this does not necessarily reduce the current symptoms a patient is experiencing.

The CDC makes a good attempt to offer guidance in the frustrating management of post-COVID syndrome. However, their clinical guidelines fail to offer specific management tools specific to treating post-COVID patients. The recommendations offered are more helpful to health in general. The fact that more specific recommendations are lacking is simply caused by the lack of knowledge of this condition at present. As more research is conducted and more knowledge obtained, new guidelines should become more detailed.

Dr. Girgis practices family medicine in South River, N.J., and is a clinical assistant professor of family medicine at Robert Wood Johnson Medical School, New Brunswick, N.J. You can contact her at [email protected].

As doctors struggled through several surges of COVID-19 infections, most of what we learned was acquired through real-life experience. While many treatment options were promoted, most flat-out failed to be real therapeutics at all. Now that we have a safe and effective vaccine, we can prevent many infections from this virus. However, we are still left to manage the many post-COVID symptoms our patients continue to suffer with.

Symptoms following infection can last for months and range widely from “brain fog,” fatigue, dyspnea, chest pain, generalized weakness, depression, and a host of others. Patients may experience one or all of these symptoms, and there is currently no good way to predict who will go on to become a COVID “long hauler”.

Following the example of being educated by COVID as it happened, the same is true for managing post-COVID symptoms. The medical community still has a poor understanding of why some people develop it and there are few evidence-based studies to support any treatment modalities.

Earlier this month, the Centers for Disease Control and Prevention issued a set of clinical guidelines addressing treatment of post-COVID symptoms, which they define as “new, recurring, or ongoing symptoms more than 4 weeks after infection, sometimes after initial symptom recovery.” It is important to note that these symptoms can occur in any degree of sickness during the acute infection, including in those who were asymptomatic. Even the actual name of this post-COVID syndrome is still being developed, with several other names being used for it as well.

While the guidelines are quite extensive, the actual clinical recommendations are still vague. For example, it is advised to let the patient know that post-COVID symptoms are still not well understood. While it is important to be transparent with patients, this does little to reassure them. Patients look to doctors, especially their primary care physicians, to guide them on the best treatment paths. Yet, we currently have none for post-COVID syndrome.

It is also advised to treat the patients’ symptoms and help improve functioning. For many diseases, doctors like to get to the root cause of the problem. Treating a symptom often masks an underlying condition. It may make the patient feel better and improve what they are capable of doing, which is important, but it also fails to unmask the real problem. It is also important to note that symptoms can be out of proportion to clinical findings and should not be dismissed: we just don’t have the answers yet.

One helpful recommendation is having a patient keep a diary of their symptoms. This will help both the patient and doctor learn what may be triggering factors. If it is, for example, exertion that induces breathlessness, perhaps the patient can gradually increase their level of activity to minimize symptoms. Additionally, a “comprehensive rehabilitation program” is also advised and this can greatly assist addressing all the issues a patient is experiencing, physically and medically.

It is also advised that management of underlying medical conditions be optimized. While this is very important, it is not something specific to post-COVID syndrome: All patients should have their underlying medical conditions well controlled. It might be that the patient is paying more attention to their overall health, which is a good thing. However, this does not necessarily reduce the current symptoms a patient is experiencing.

The CDC makes a good attempt to offer guidance in the frustrating management of post-COVID syndrome. However, their clinical guidelines fail to offer specific management tools specific to treating post-COVID patients. The recommendations offered are more helpful to health in general. The fact that more specific recommendations are lacking is simply caused by the lack of knowledge of this condition at present. As more research is conducted and more knowledge obtained, new guidelines should become more detailed.

Dr. Girgis practices family medicine in South River, N.J., and is a clinical assistant professor of family medicine at Robert Wood Johnson Medical School, New Brunswick, N.J. You can contact her at [email protected].