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Successful Recruitment of VA Patients in Precision Medicine Research Through Passive Recruitment Efforts
Background
We sought to evaluate passive recruitment efforts of VA patients into a precision medicine research program. Access to clinical trials and other research opportunities is important to discovering new disease treatments and better ways to detect, diagnose, and reduce disease risk. The WISDOM (Women Informed to Screen Depending on Measures of risk) Study is a multi-site, pragmatic trial with webbased participation based at the University of California at San Francisco (UCSF) that aims to move breast cancer screening away from its current one-size-fitsall approach to one that is personalized based on each woman’s individual risk.
Methods
We created a hub and spoke recruitment model with the San Francisco VA Medical Center (SFVAMC) serving as the central hub of passive recruitment activities and eligible VA facilities that agreed to participate serving as the spoke recruitment sites. Eligible facilities had at least 3,000 women patients, VA clinical genetic services available, a site lead from the VA Women’s Health-Practice-Based Research Network, and mammography on site. Site participation involved permission for the research team to email eligible patients (women aged 40-74 without prior breast cancer diagnosis) about the WISDOM Study. We evaluated the effectiveness of the recruitment by assessing trends in enrollment and monitoring participation of VA patients in the WISDOM Study. Analysis: Pre/post frequencies of women consenting to participate in the WISDOM Study.
Results
From 5/24/2021 through 6/21/2021, we emailed 27,061 eligible VA patients from six participating VA facilities. Prior to the VA emailing, an average of 22 women per week consented to participating in the WISDOM Study and none were Veterans. After the first month of the VA emailing, an average of 186 women per week consented – a 7.5-fold increase. Additionally, during the first month of VA emailing, 81% of women registering with the WISDOM Study said they heard about the study from the VA.
Implications
The VA has recently approved of emailing as a method for recruiting research subjects. Our results demonstrate this is a feasible approach for precision medicine research, a growing area of research in VA and at academic affiliates.
Background
We sought to evaluate passive recruitment efforts of VA patients into a precision medicine research program. Access to clinical trials and other research opportunities is important to discovering new disease treatments and better ways to detect, diagnose, and reduce disease risk. The WISDOM (Women Informed to Screen Depending on Measures of risk) Study is a multi-site, pragmatic trial with webbased participation based at the University of California at San Francisco (UCSF) that aims to move breast cancer screening away from its current one-size-fitsall approach to one that is personalized based on each woman’s individual risk.
Methods
We created a hub and spoke recruitment model with the San Francisco VA Medical Center (SFVAMC) serving as the central hub of passive recruitment activities and eligible VA facilities that agreed to participate serving as the spoke recruitment sites. Eligible facilities had at least 3,000 women patients, VA clinical genetic services available, a site lead from the VA Women’s Health-Practice-Based Research Network, and mammography on site. Site participation involved permission for the research team to email eligible patients (women aged 40-74 without prior breast cancer diagnosis) about the WISDOM Study. We evaluated the effectiveness of the recruitment by assessing trends in enrollment and monitoring participation of VA patients in the WISDOM Study. Analysis: Pre/post frequencies of women consenting to participate in the WISDOM Study.
Results
From 5/24/2021 through 6/21/2021, we emailed 27,061 eligible VA patients from six participating VA facilities. Prior to the VA emailing, an average of 22 women per week consented to participating in the WISDOM Study and none were Veterans. After the first month of the VA emailing, an average of 186 women per week consented – a 7.5-fold increase. Additionally, during the first month of VA emailing, 81% of women registering with the WISDOM Study said they heard about the study from the VA.
Implications
The VA has recently approved of emailing as a method for recruiting research subjects. Our results demonstrate this is a feasible approach for precision medicine research, a growing area of research in VA and at academic affiliates.
Background
We sought to evaluate passive recruitment efforts of VA patients into a precision medicine research program. Access to clinical trials and other research opportunities is important to discovering new disease treatments and better ways to detect, diagnose, and reduce disease risk. The WISDOM (Women Informed to Screen Depending on Measures of risk) Study is a multi-site, pragmatic trial with webbased participation based at the University of California at San Francisco (UCSF) that aims to move breast cancer screening away from its current one-size-fitsall approach to one that is personalized based on each woman’s individual risk.
Methods
We created a hub and spoke recruitment model with the San Francisco VA Medical Center (SFVAMC) serving as the central hub of passive recruitment activities and eligible VA facilities that agreed to participate serving as the spoke recruitment sites. Eligible facilities had at least 3,000 women patients, VA clinical genetic services available, a site lead from the VA Women’s Health-Practice-Based Research Network, and mammography on site. Site participation involved permission for the research team to email eligible patients (women aged 40-74 without prior breast cancer diagnosis) about the WISDOM Study. We evaluated the effectiveness of the recruitment by assessing trends in enrollment and monitoring participation of VA patients in the WISDOM Study. Analysis: Pre/post frequencies of women consenting to participate in the WISDOM Study.
Results
From 5/24/2021 through 6/21/2021, we emailed 27,061 eligible VA patients from six participating VA facilities. Prior to the VA emailing, an average of 22 women per week consented to participating in the WISDOM Study and none were Veterans. After the first month of the VA emailing, an average of 186 women per week consented – a 7.5-fold increase. Additionally, during the first month of VA emailing, 81% of women registering with the WISDOM Study said they heard about the study from the VA.
Implications
The VA has recently approved of emailing as a method for recruiting research subjects. Our results demonstrate this is a feasible approach for precision medicine research, a growing area of research in VA and at academic affiliates.
COVID-19 vaccines in pregnancy may protect baby, too
Women who receive COVID-19 vaccines during pregnancy pass antibodies to their babies, which could protect newborns from the disease, research has shown.
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Researchers with New York University Langone Health conducted a study that included pregnant women who had received at least one dose of an mRNA COVID-19 vaccine (Pfizer/BioNTech or Moderna) by June 4.
All neonates had antibodies to the spike protein at high titers, the researchers found.
Unlike similar prior studies, the researchers also looked for antibodies to the nucleocapsid protein, which would have indicated the presence of antibodies from natural COVID-19 infection. They did not detect antibodies to the nucleocapsid protein, and the lack of these antibodies suggests that the antibodies to the spike protein resulted from vaccination and not from prior infection, the researchers said.
The participants had a median time from completion of the vaccine series to delivery of 13 weeks. The study was published online in the American Journal of Obstetrics & Gynecology MFM.
“The presence of these anti-spike antibodies in the cord blood should, at least in theory, offer these newborns some degree of protection,” said study investigator Ashley S. Roman, MD, director of the division of maternal-fetal medicine at NYU Langone Health. “While the primary rationale for vaccination during pregnancy is to keep moms healthy and keep moms out of the hospital, the outstanding question to us was whether there is any fetal or neonatal benefit conferred by receiving the vaccine during pregnancy.”
Questions remain about the degree and durability of protection for newborns from these antibodies. An ongoing study, MOMI-VAX, aims to systematically measure antibody levels in mothers who receive COVID-19 vaccines during pregnancy and in their babies over time.
The present study contributes welcome preliminary evidence suggesting a benefit to infants, said Emily Adhikari, MD, of the University of Texas Southwestern Medical Center in Dallas, who was not involved in the study.
Still, “the main concern and our priority as obstetricians is to vaccinate pregnant women to protect them from severe or critical illness,” she said.
Although most individuals infected with SARS-CoV-2 recover, a significant portion of pregnant women get seriously sick, Dr. Adhikari said. “With this recent Delta surge, we are seeing more pregnant patients who are sicker,” said Dr. Adhikari, who has published research from one hospital describing this trend.
When weighing whether patients should receive COVID-19 vaccines in pregnancy, the risks from infection have outweighed any risk from vaccination to such an extent that there is “not a comparison to make,” Dr. Adhikari said. “The risks of the infection are so much higher.
“For me, it is a matter of making sure that my patient understands that we have really good safety data on these vaccines and there is no reason to think that a pregnant person would be harmed by them. On the contrary, the benefit is to protect and maybe even save your life,” Dr. Adhikari said. “And now we have more evidence that the fetus may also benefit.”
The rationale for vaccinations during pregnancy can vary, Dr. Roman said. Flu shots in pregnancy mainly are intended to protect the mother, though they confer protection for newborns as well. With the whooping cough vaccine given in the third trimester, however, the primary aim is to protect the baby from whooping cough in the first months of life, Dr. Roman said.
“I think it is really important for pregnant women to understand that antibodies crossing the placenta is a good thing,” she added.
As patients who already have received COVID-19 vaccines become pregnant and may become eligible for a booster dose, Dr. Adhikari will offer it, she said, though she has confidence in the protection provided by the initial immune response.
Dr. Roman and Dr. Adhikari had no disclosures.
Women who receive COVID-19 vaccines during pregnancy pass antibodies to their babies, which could protect newborns from the disease, research has shown.
.
Researchers with New York University Langone Health conducted a study that included pregnant women who had received at least one dose of an mRNA COVID-19 vaccine (Pfizer/BioNTech or Moderna) by June 4.
All neonates had antibodies to the spike protein at high titers, the researchers found.
Unlike similar prior studies, the researchers also looked for antibodies to the nucleocapsid protein, which would have indicated the presence of antibodies from natural COVID-19 infection. They did not detect antibodies to the nucleocapsid protein, and the lack of these antibodies suggests that the antibodies to the spike protein resulted from vaccination and not from prior infection, the researchers said.
The participants had a median time from completion of the vaccine series to delivery of 13 weeks. The study was published online in the American Journal of Obstetrics & Gynecology MFM.
“The presence of these anti-spike antibodies in the cord blood should, at least in theory, offer these newborns some degree of protection,” said study investigator Ashley S. Roman, MD, director of the division of maternal-fetal medicine at NYU Langone Health. “While the primary rationale for vaccination during pregnancy is to keep moms healthy and keep moms out of the hospital, the outstanding question to us was whether there is any fetal or neonatal benefit conferred by receiving the vaccine during pregnancy.”
Questions remain about the degree and durability of protection for newborns from these antibodies. An ongoing study, MOMI-VAX, aims to systematically measure antibody levels in mothers who receive COVID-19 vaccines during pregnancy and in their babies over time.
The present study contributes welcome preliminary evidence suggesting a benefit to infants, said Emily Adhikari, MD, of the University of Texas Southwestern Medical Center in Dallas, who was not involved in the study.
Still, “the main concern and our priority as obstetricians is to vaccinate pregnant women to protect them from severe or critical illness,” she said.
Although most individuals infected with SARS-CoV-2 recover, a significant portion of pregnant women get seriously sick, Dr. Adhikari said. “With this recent Delta surge, we are seeing more pregnant patients who are sicker,” said Dr. Adhikari, who has published research from one hospital describing this trend.
When weighing whether patients should receive COVID-19 vaccines in pregnancy, the risks from infection have outweighed any risk from vaccination to such an extent that there is “not a comparison to make,” Dr. Adhikari said. “The risks of the infection are so much higher.
“For me, it is a matter of making sure that my patient understands that we have really good safety data on these vaccines and there is no reason to think that a pregnant person would be harmed by them. On the contrary, the benefit is to protect and maybe even save your life,” Dr. Adhikari said. “And now we have more evidence that the fetus may also benefit.”
The rationale for vaccinations during pregnancy can vary, Dr. Roman said. Flu shots in pregnancy mainly are intended to protect the mother, though they confer protection for newborns as well. With the whooping cough vaccine given in the third trimester, however, the primary aim is to protect the baby from whooping cough in the first months of life, Dr. Roman said.
“I think it is really important for pregnant women to understand that antibodies crossing the placenta is a good thing,” she added.
As patients who already have received COVID-19 vaccines become pregnant and may become eligible for a booster dose, Dr. Adhikari will offer it, she said, though she has confidence in the protection provided by the initial immune response.
Dr. Roman and Dr. Adhikari had no disclosures.
Women who receive COVID-19 vaccines during pregnancy pass antibodies to their babies, which could protect newborns from the disease, research has shown.
.
Researchers with New York University Langone Health conducted a study that included pregnant women who had received at least one dose of an mRNA COVID-19 vaccine (Pfizer/BioNTech or Moderna) by June 4.
All neonates had antibodies to the spike protein at high titers, the researchers found.
Unlike similar prior studies, the researchers also looked for antibodies to the nucleocapsid protein, which would have indicated the presence of antibodies from natural COVID-19 infection. They did not detect antibodies to the nucleocapsid protein, and the lack of these antibodies suggests that the antibodies to the spike protein resulted from vaccination and not from prior infection, the researchers said.
The participants had a median time from completion of the vaccine series to delivery of 13 weeks. The study was published online in the American Journal of Obstetrics & Gynecology MFM.
“The presence of these anti-spike antibodies in the cord blood should, at least in theory, offer these newborns some degree of protection,” said study investigator Ashley S. Roman, MD, director of the division of maternal-fetal medicine at NYU Langone Health. “While the primary rationale for vaccination during pregnancy is to keep moms healthy and keep moms out of the hospital, the outstanding question to us was whether there is any fetal or neonatal benefit conferred by receiving the vaccine during pregnancy.”
Questions remain about the degree and durability of protection for newborns from these antibodies. An ongoing study, MOMI-VAX, aims to systematically measure antibody levels in mothers who receive COVID-19 vaccines during pregnancy and in their babies over time.
The present study contributes welcome preliminary evidence suggesting a benefit to infants, said Emily Adhikari, MD, of the University of Texas Southwestern Medical Center in Dallas, who was not involved in the study.
Still, “the main concern and our priority as obstetricians is to vaccinate pregnant women to protect them from severe or critical illness,” she said.
Although most individuals infected with SARS-CoV-2 recover, a significant portion of pregnant women get seriously sick, Dr. Adhikari said. “With this recent Delta surge, we are seeing more pregnant patients who are sicker,” said Dr. Adhikari, who has published research from one hospital describing this trend.
When weighing whether patients should receive COVID-19 vaccines in pregnancy, the risks from infection have outweighed any risk from vaccination to such an extent that there is “not a comparison to make,” Dr. Adhikari said. “The risks of the infection are so much higher.
“For me, it is a matter of making sure that my patient understands that we have really good safety data on these vaccines and there is no reason to think that a pregnant person would be harmed by them. On the contrary, the benefit is to protect and maybe even save your life,” Dr. Adhikari said. “And now we have more evidence that the fetus may also benefit.”
The rationale for vaccinations during pregnancy can vary, Dr. Roman said. Flu shots in pregnancy mainly are intended to protect the mother, though they confer protection for newborns as well. With the whooping cough vaccine given in the third trimester, however, the primary aim is to protect the baby from whooping cough in the first months of life, Dr. Roman said.
“I think it is really important for pregnant women to understand that antibodies crossing the placenta is a good thing,” she added.
As patients who already have received COVID-19 vaccines become pregnant and may become eligible for a booster dose, Dr. Adhikari will offer it, she said, though she has confidence in the protection provided by the initial immune response.
Dr. Roman and Dr. Adhikari had no disclosures.
FROM AMERICAN JOURNAL OF OBSTETRICS & GYNECOLOGY MFM
When children and teens with cancer get COVID-19
Although most children and adolescents with cancer have mild illness from COVID-19 infection, some do experience severe disease and a small percentage even die, according to a recent analysis.
The findings, published online in Lancet Oncology, represent the first global registry data spanning different income groups to report COVID-19 outcomes in pediatric oncology patients.
“We wanted to create a global pool of evidence to answer the question: Do we see severe [COVID-19] infection [in children with cancer]?” corresponding author Sheena Mukkada, MD, St. Jude Children’s Research Hospital, Memphis, said in an interview.
In a cohort of 1,319 pediatric patients followed for 30 days, Dr. Mukkada and colleagues reported that 80% of these patients had asymptomatic to moderate disease from COVID-19, while 1 in 5 experienced severe or critical illness and almost 4% died – four times the mortality rate observed in published cohorts of general pediatric patients.
The results highlight that “children and adolescents with cancer generally recover without incident from COVID-19, but can have a severe course of infection,” the authors concluded.
And knowing that some children can get very sick, investigators wanted “to identify who these patients are so that we can prioritize and protect that group,” she added.
Echoing that sentiment, Kathy Pritchard-Jones, MD, president of the International Society of Paediatric Oncology and coauthor on the study, noted in a press release that, “by working together to create this global registry, we have enabled hospitals around the world to rapidly share and learn how COVID-19 is affecting children with cancer.”
Dr. Pritchard-Jones commented that overall these results provide reassurance that “many children can continue their cancer treatment safely, but they also highlight important clinical features that may predict a more severe clinical course and the need for greater vigilance for some patients.”
Inside the Global Registry data
The Global Registry of COVID-19 in Childhood Cancer, created jointly by St. Jude Children’s Research Hospital and SIOP, included data from 131 institutions in 45 countries. Children recruited into the registry between April 2020 and February 2021 ranged in age from infancy to 18 years old.
Most patients remained asymptomatic (35%) or experienced mild to moderate illness (45%), though 20% did develop severe or critical illness.
The investigators highlighted several factors associated with a greater risk of developing more severe illness from COVID-19, which included cancer type, intensity of therapy, age, absolute lymphocyte count, and presence of comorbidities or COVID-19 symptoms.
Notably, more than 80% of either severe or critical infections occurred in patients with hematologic malignancies – with 56% of cases in patients with acute lymphoblastic lymphoma or acute lymphoblastic leukemia – followed by extracranial solid tumors (15.8%), and central nervous system tumors (2.7%).
In patients with acute lymphoblastic leukemia or acute lymphoblastic lymphoma, severe or critical disease was most common in those receiving induction therapy (30%), relapse or refractory therapy (30%), and those in the maintenance or continuation phase of therapy (19%).
Older age was associated with a higher likelihood of having severe disease – with the lowest risk in infants (9.7%) and the highest in the 15- to 18-year-old cohort (27.3%).
Patients with lymphopenia who had an absolute lymphocyte count of 300 cells per mm3 or less and an absolute neutrophil count of 500 cells per mm3 or more also had an elevated risk of severe illness from COVID-19.
Regarding whether the presence of lymphopenia or neutropenia should change the treatment approach, Dr. Mukkada noted that, when possible, these patients should receive antiviral treatment, such as remdesivir, if the center has antivirals, or be prioritized for hospital admission.
Modifying cancer treatment might be recommended if patients are highly lymphopenic or have very low neutrophil counts, but a more effective strategy is simply to ensure that age-eligible children and adolescents with cancer or who have had a hematopoietic stem-cell transplantation have been fully vaccinated against COVID-19. For children who are not yet age-eligible, everyone around them should be vaccinated.
Pediatric patients in low- and middle-income countries were also more likely to have severe or critical outcomes from COVID-19 (41.7%), compared with patients in other income groups (23.9%).
The impact of COVID-19 “has been felt in every corner of the world, but particularly in low- and middle-income countries, compared to high-income countries,” senior author Carlos Rodriguez-Galindo, MD, global director at St. Jude, said in a statement.
In terms of the intersection of cancer treatment and COVID diagnosis, almost 83% of pediatric patients were receiving treatment for their cancer. Chemotherapy was withheld in about 45% of these patients and some modification to the treatment regimen occurred in almost 56% of participants on active therapy.
“Treatment modifications were least common in patients from upper-middle–income countries, compared with other income groups,” the authors wrote.
Although an interesting observation, Dr. Mukkada noted that the registry data could not explain why treatment modifications occurred less frequently in upper-middle income countries as opposed to high-income and lower-income countries.
U.K. Monitoring Project
Not all studies, however, have found that COVID-19 infection is significantly more severe in children with cancer. In a 2020 report from the U.K. Paediatric Coronavirus Cancer Monitoring Project, researchers evaluated all children in the United Kingdom under the age of 16 diagnosed with COVID and cancer.
“[Given that] we had complete coverage of every center in the U.K. that cares for children with cancer, we are confident that we picked up at least all the severe or critical cases,” lead author Gerard Millen, MD, honorary clinical research fellow, University of Birmingham (England), said in an interview.
Between March 2020 and July 2020, Dr. Millen and colleagues identified 54 positive cases of COVID-19, 15 (28%) of which were asymptomatic, 34 (63%) mild, and 4 (7.4%) severe or critical – more in line with the incidence of severe illness reported in the general pediatric population.
“Thankfully, we had no children with cancer in the U.K. who died from COVID-19,” Dr. Millen noted. “Overall, in the U.K., we have taken the approach that the majority of children with cancer in this country are at very low risk from COVID-19 and that we do not have good evidence to modify their treatment.”
Dr. Millen pointed out that the data in the U.K. study were “remarkably similar” to those from the high-income countries in the global St. Jude/SIOP cohort, where 7.4% of patients in that cohort had severe or critical disease, compared with 7.4% of patients from their own U.K. cohort.
“I think many of the key differences between the two cohorts reflect the fact that access to treatment in many low- to middle-income countries is more challenging with many factors contributing to overall poorer outcomes for both cancer and noncancer metrics,” Dr. Millen said.
Both the U.K. and registry studies were performed prior to vaccinations becoming available to older children, and before the emergence of certain variants, including the Delta variant, which is responsible for the most recent surge of COVID-19 infections around the world.
Data on COVID-19 vaccination in children with cancer are limited but promising so far.
As for whether the Delta variant might affect outcomes for children with cancer and COVID-19, Dr. Mukkada could only speculate, but she noted that “what we are hearing anecdotally about the [Delta] disease being more severe, even in patients who don’t have cancer, is leading us to say that we can’t close the registry yet. We are still actively enrolling children.”
The study was funded by the American Lebanese Syrian Associated Charities and the National Cancer Institute. The study authors and Dr. Millen disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Although most children and adolescents with cancer have mild illness from COVID-19 infection, some do experience severe disease and a small percentage even die, according to a recent analysis.
The findings, published online in Lancet Oncology, represent the first global registry data spanning different income groups to report COVID-19 outcomes in pediatric oncology patients.
“We wanted to create a global pool of evidence to answer the question: Do we see severe [COVID-19] infection [in children with cancer]?” corresponding author Sheena Mukkada, MD, St. Jude Children’s Research Hospital, Memphis, said in an interview.
In a cohort of 1,319 pediatric patients followed for 30 days, Dr. Mukkada and colleagues reported that 80% of these patients had asymptomatic to moderate disease from COVID-19, while 1 in 5 experienced severe or critical illness and almost 4% died – four times the mortality rate observed in published cohorts of general pediatric patients.
The results highlight that “children and adolescents with cancer generally recover without incident from COVID-19, but can have a severe course of infection,” the authors concluded.
And knowing that some children can get very sick, investigators wanted “to identify who these patients are so that we can prioritize and protect that group,” she added.
Echoing that sentiment, Kathy Pritchard-Jones, MD, president of the International Society of Paediatric Oncology and coauthor on the study, noted in a press release that, “by working together to create this global registry, we have enabled hospitals around the world to rapidly share and learn how COVID-19 is affecting children with cancer.”
Dr. Pritchard-Jones commented that overall these results provide reassurance that “many children can continue their cancer treatment safely, but they also highlight important clinical features that may predict a more severe clinical course and the need for greater vigilance for some patients.”
Inside the Global Registry data
The Global Registry of COVID-19 in Childhood Cancer, created jointly by St. Jude Children’s Research Hospital and SIOP, included data from 131 institutions in 45 countries. Children recruited into the registry between April 2020 and February 2021 ranged in age from infancy to 18 years old.
Most patients remained asymptomatic (35%) or experienced mild to moderate illness (45%), though 20% did develop severe or critical illness.
The investigators highlighted several factors associated with a greater risk of developing more severe illness from COVID-19, which included cancer type, intensity of therapy, age, absolute lymphocyte count, and presence of comorbidities or COVID-19 symptoms.
Notably, more than 80% of either severe or critical infections occurred in patients with hematologic malignancies – with 56% of cases in patients with acute lymphoblastic lymphoma or acute lymphoblastic leukemia – followed by extracranial solid tumors (15.8%), and central nervous system tumors (2.7%).
In patients with acute lymphoblastic leukemia or acute lymphoblastic lymphoma, severe or critical disease was most common in those receiving induction therapy (30%), relapse or refractory therapy (30%), and those in the maintenance or continuation phase of therapy (19%).
Older age was associated with a higher likelihood of having severe disease – with the lowest risk in infants (9.7%) and the highest in the 15- to 18-year-old cohort (27.3%).
Patients with lymphopenia who had an absolute lymphocyte count of 300 cells per mm3 or less and an absolute neutrophil count of 500 cells per mm3 or more also had an elevated risk of severe illness from COVID-19.
Regarding whether the presence of lymphopenia or neutropenia should change the treatment approach, Dr. Mukkada noted that, when possible, these patients should receive antiviral treatment, such as remdesivir, if the center has antivirals, or be prioritized for hospital admission.
Modifying cancer treatment might be recommended if patients are highly lymphopenic or have very low neutrophil counts, but a more effective strategy is simply to ensure that age-eligible children and adolescents with cancer or who have had a hematopoietic stem-cell transplantation have been fully vaccinated against COVID-19. For children who are not yet age-eligible, everyone around them should be vaccinated.
Pediatric patients in low- and middle-income countries were also more likely to have severe or critical outcomes from COVID-19 (41.7%), compared with patients in other income groups (23.9%).
The impact of COVID-19 “has been felt in every corner of the world, but particularly in low- and middle-income countries, compared to high-income countries,” senior author Carlos Rodriguez-Galindo, MD, global director at St. Jude, said in a statement.
In terms of the intersection of cancer treatment and COVID diagnosis, almost 83% of pediatric patients were receiving treatment for their cancer. Chemotherapy was withheld in about 45% of these patients and some modification to the treatment regimen occurred in almost 56% of participants on active therapy.
“Treatment modifications were least common in patients from upper-middle–income countries, compared with other income groups,” the authors wrote.
Although an interesting observation, Dr. Mukkada noted that the registry data could not explain why treatment modifications occurred less frequently in upper-middle income countries as opposed to high-income and lower-income countries.
U.K. Monitoring Project
Not all studies, however, have found that COVID-19 infection is significantly more severe in children with cancer. In a 2020 report from the U.K. Paediatric Coronavirus Cancer Monitoring Project, researchers evaluated all children in the United Kingdom under the age of 16 diagnosed with COVID and cancer.
“[Given that] we had complete coverage of every center in the U.K. that cares for children with cancer, we are confident that we picked up at least all the severe or critical cases,” lead author Gerard Millen, MD, honorary clinical research fellow, University of Birmingham (England), said in an interview.
Between March 2020 and July 2020, Dr. Millen and colleagues identified 54 positive cases of COVID-19, 15 (28%) of which were asymptomatic, 34 (63%) mild, and 4 (7.4%) severe or critical – more in line with the incidence of severe illness reported in the general pediatric population.
“Thankfully, we had no children with cancer in the U.K. who died from COVID-19,” Dr. Millen noted. “Overall, in the U.K., we have taken the approach that the majority of children with cancer in this country are at very low risk from COVID-19 and that we do not have good evidence to modify their treatment.”
Dr. Millen pointed out that the data in the U.K. study were “remarkably similar” to those from the high-income countries in the global St. Jude/SIOP cohort, where 7.4% of patients in that cohort had severe or critical disease, compared with 7.4% of patients from their own U.K. cohort.
“I think many of the key differences between the two cohorts reflect the fact that access to treatment in many low- to middle-income countries is more challenging with many factors contributing to overall poorer outcomes for both cancer and noncancer metrics,” Dr. Millen said.
Both the U.K. and registry studies were performed prior to vaccinations becoming available to older children, and before the emergence of certain variants, including the Delta variant, which is responsible for the most recent surge of COVID-19 infections around the world.
Data on COVID-19 vaccination in children with cancer are limited but promising so far.
As for whether the Delta variant might affect outcomes for children with cancer and COVID-19, Dr. Mukkada could only speculate, but she noted that “what we are hearing anecdotally about the [Delta] disease being more severe, even in patients who don’t have cancer, is leading us to say that we can’t close the registry yet. We are still actively enrolling children.”
The study was funded by the American Lebanese Syrian Associated Charities and the National Cancer Institute. The study authors and Dr. Millen disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Although most children and adolescents with cancer have mild illness from COVID-19 infection, some do experience severe disease and a small percentage even die, according to a recent analysis.
The findings, published online in Lancet Oncology, represent the first global registry data spanning different income groups to report COVID-19 outcomes in pediatric oncology patients.
“We wanted to create a global pool of evidence to answer the question: Do we see severe [COVID-19] infection [in children with cancer]?” corresponding author Sheena Mukkada, MD, St. Jude Children’s Research Hospital, Memphis, said in an interview.
In a cohort of 1,319 pediatric patients followed for 30 days, Dr. Mukkada and colleagues reported that 80% of these patients had asymptomatic to moderate disease from COVID-19, while 1 in 5 experienced severe or critical illness and almost 4% died – four times the mortality rate observed in published cohorts of general pediatric patients.
The results highlight that “children and adolescents with cancer generally recover without incident from COVID-19, but can have a severe course of infection,” the authors concluded.
And knowing that some children can get very sick, investigators wanted “to identify who these patients are so that we can prioritize and protect that group,” she added.
Echoing that sentiment, Kathy Pritchard-Jones, MD, president of the International Society of Paediatric Oncology and coauthor on the study, noted in a press release that, “by working together to create this global registry, we have enabled hospitals around the world to rapidly share and learn how COVID-19 is affecting children with cancer.”
Dr. Pritchard-Jones commented that overall these results provide reassurance that “many children can continue their cancer treatment safely, but they also highlight important clinical features that may predict a more severe clinical course and the need for greater vigilance for some patients.”
Inside the Global Registry data
The Global Registry of COVID-19 in Childhood Cancer, created jointly by St. Jude Children’s Research Hospital and SIOP, included data from 131 institutions in 45 countries. Children recruited into the registry between April 2020 and February 2021 ranged in age from infancy to 18 years old.
Most patients remained asymptomatic (35%) or experienced mild to moderate illness (45%), though 20% did develop severe or critical illness.
The investigators highlighted several factors associated with a greater risk of developing more severe illness from COVID-19, which included cancer type, intensity of therapy, age, absolute lymphocyte count, and presence of comorbidities or COVID-19 symptoms.
Notably, more than 80% of either severe or critical infections occurred in patients with hematologic malignancies – with 56% of cases in patients with acute lymphoblastic lymphoma or acute lymphoblastic leukemia – followed by extracranial solid tumors (15.8%), and central nervous system tumors (2.7%).
In patients with acute lymphoblastic leukemia or acute lymphoblastic lymphoma, severe or critical disease was most common in those receiving induction therapy (30%), relapse or refractory therapy (30%), and those in the maintenance or continuation phase of therapy (19%).
Older age was associated with a higher likelihood of having severe disease – with the lowest risk in infants (9.7%) and the highest in the 15- to 18-year-old cohort (27.3%).
Patients with lymphopenia who had an absolute lymphocyte count of 300 cells per mm3 or less and an absolute neutrophil count of 500 cells per mm3 or more also had an elevated risk of severe illness from COVID-19.
Regarding whether the presence of lymphopenia or neutropenia should change the treatment approach, Dr. Mukkada noted that, when possible, these patients should receive antiviral treatment, such as remdesivir, if the center has antivirals, or be prioritized for hospital admission.
Modifying cancer treatment might be recommended if patients are highly lymphopenic or have very low neutrophil counts, but a more effective strategy is simply to ensure that age-eligible children and adolescents with cancer or who have had a hematopoietic stem-cell transplantation have been fully vaccinated against COVID-19. For children who are not yet age-eligible, everyone around them should be vaccinated.
Pediatric patients in low- and middle-income countries were also more likely to have severe or critical outcomes from COVID-19 (41.7%), compared with patients in other income groups (23.9%).
The impact of COVID-19 “has been felt in every corner of the world, but particularly in low- and middle-income countries, compared to high-income countries,” senior author Carlos Rodriguez-Galindo, MD, global director at St. Jude, said in a statement.
In terms of the intersection of cancer treatment and COVID diagnosis, almost 83% of pediatric patients were receiving treatment for their cancer. Chemotherapy was withheld in about 45% of these patients and some modification to the treatment regimen occurred in almost 56% of participants on active therapy.
“Treatment modifications were least common in patients from upper-middle–income countries, compared with other income groups,” the authors wrote.
Although an interesting observation, Dr. Mukkada noted that the registry data could not explain why treatment modifications occurred less frequently in upper-middle income countries as opposed to high-income and lower-income countries.
U.K. Monitoring Project
Not all studies, however, have found that COVID-19 infection is significantly more severe in children with cancer. In a 2020 report from the U.K. Paediatric Coronavirus Cancer Monitoring Project, researchers evaluated all children in the United Kingdom under the age of 16 diagnosed with COVID and cancer.
“[Given that] we had complete coverage of every center in the U.K. that cares for children with cancer, we are confident that we picked up at least all the severe or critical cases,” lead author Gerard Millen, MD, honorary clinical research fellow, University of Birmingham (England), said in an interview.
Between March 2020 and July 2020, Dr. Millen and colleagues identified 54 positive cases of COVID-19, 15 (28%) of which were asymptomatic, 34 (63%) mild, and 4 (7.4%) severe or critical – more in line with the incidence of severe illness reported in the general pediatric population.
“Thankfully, we had no children with cancer in the U.K. who died from COVID-19,” Dr. Millen noted. “Overall, in the U.K., we have taken the approach that the majority of children with cancer in this country are at very low risk from COVID-19 and that we do not have good evidence to modify their treatment.”
Dr. Millen pointed out that the data in the U.K. study were “remarkably similar” to those from the high-income countries in the global St. Jude/SIOP cohort, where 7.4% of patients in that cohort had severe or critical disease, compared with 7.4% of patients from their own U.K. cohort.
“I think many of the key differences between the two cohorts reflect the fact that access to treatment in many low- to middle-income countries is more challenging with many factors contributing to overall poorer outcomes for both cancer and noncancer metrics,” Dr. Millen said.
Both the U.K. and registry studies were performed prior to vaccinations becoming available to older children, and before the emergence of certain variants, including the Delta variant, which is responsible for the most recent surge of COVID-19 infections around the world.
Data on COVID-19 vaccination in children with cancer are limited but promising so far.
As for whether the Delta variant might affect outcomes for children with cancer and COVID-19, Dr. Mukkada could only speculate, but she noted that “what we are hearing anecdotally about the [Delta] disease being more severe, even in patients who don’t have cancer, is leading us to say that we can’t close the registry yet. We are still actively enrolling children.”
The study was funded by the American Lebanese Syrian Associated Charities and the National Cancer Institute. The study authors and Dr. Millen disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Immunotherapy for cancer patients with poor PS needs a rethink
The findings have prompted an expert to argue against the use of immunotherapy for such patients, who may have little time left and very little chance of benefiting.
“It is quite clear from clinical practice that most patients with limited PS do very poorly and do not benefit from immune check point inhibitors (ICI),” Jason Luke, MD, UPMC Hillman Cancer Center and the University of Pittsburgh, said in an email.
“So, my strong opinion is that patients should not be getting an immunotherapy just because it might not cause as many side effects as chemotherapy,” he added.
“Instead of giving an immunotherapy with little chance of success, patients and families deserve to have a direct conversation about what realistic expectations [might be] and how we as the oncology community can support them to achieve whatever their personal goals are in the time that they have left,” he emphasized.
Dr. Luke was the lead author of an editorial in which he commented on the study. Both the study and the editorial were published online in JCO Oncology Practice.
Variety of cancers
The study was conducted by Mridula Krishnan, MD, Nebraska Medicine Fred and Pamela Buffett Cancer Center, Omaha, Nebraska, and colleagues.
The team reviewed 257 patients who had been treated with either a programmed cell death protein–1 inhibitor or programmed cell death–ligand-1 inhibitor for a variety of advanced cancers. The drugs included pembrolizumab (Keytruda), nivolumab (Opdivo), atezolizumab (Tecentique), durvalumab (Imfinzi), and avelumab (Bavencio).
Most of the patients (71%) had good PS, with an Eastern Cooperative Oncology Group (ECOG) PS of 0-1 on initiation of immunotherapy; 29% of patients had poor PS, with an ECOG PS of greater than or equal to 2.
“The primary outcome was OS stratified by ECOG PS 0-1 versus ≥2,” note the authors. Across all tumor types, OS was superior for patients in the ECOG 0-1 PS group, the investigators note. The median OS was 12.6 months, compared with only 3.1 months for patients in the ECOG greater than or equal to 2 group (P < .001).
Moreover, overall response rates for patients with a poor PS were low. Only 8%, or 6 of 75 patients with an ECOG PS of greater than or equal to 2, achieved an objective response by RECIST criteria.
This compared to an overall response rate of 23% for patients with an ECOG PS of 0-1, the investigators note (P = .005).
Interestingly, the hospice referral rate for patients with a poor PS (67%) was similar to that of patients with a PS of 1-2 (61.9%), Dr. Krishnan and colleagues observe.
Those with a poor PS were more like to die in-hospital (28.6%) than were patients with a good PS (15.1%; P = .035). The authors point out that it is well known that outcomes with chemotherapy are worse among patients who experience a decline in functional reserve, owing to increased susceptibility to toxicity and complications.
“Regardless of age, patients with ECOG PS >2 usually have poor tolerability to chemotherapy, and this correlates with worse survival outcome,” they emphasize. There is as yet no clear guidance regarding the impact of PS on ICI treatment response, although “there should be,” Dr. Luke believes.
“In a patient with declining performance status, especially ECOG PS 3-4 but potentially 2 as well, there is little likelihood that the functional and immune reserve of the patient will be adequate to mount a robust antitumor response,” he elaborated.
“It’s not impossible, but trying for it should not come at the expense of engaging about end-of-life care and maximizing the palliative opportunities that many only have a short window of time in which to pursue,” he added.
Again, Dr. Luke strongly believes that just giving an ICI without engaging in a frank conversation with the patient and their families – which happens all too often, he feels – is absolutely not the way to go when treating patients with a poor PS and little time left.
“Patients and families might be better served by having a more direct and frank conversation about what the likelihood [is] that ICI therapy will actually do,” Dr. Luke stressed.
In their editorial, Dr. Luke and colleagues write: “Overall, we as an oncology community need to improve our communication with patients regarding goals of care and end-of-life considerations as opposed to reflexive treatment initiation,” he writes.
“Our duty, first and foremost, should focus on the person sitting in front of us – taking a step back may be the best way to move forward with compassionate care,” they add.
The authors and editorialists have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The findings have prompted an expert to argue against the use of immunotherapy for such patients, who may have little time left and very little chance of benefiting.
“It is quite clear from clinical practice that most patients with limited PS do very poorly and do not benefit from immune check point inhibitors (ICI),” Jason Luke, MD, UPMC Hillman Cancer Center and the University of Pittsburgh, said in an email.
“So, my strong opinion is that patients should not be getting an immunotherapy just because it might not cause as many side effects as chemotherapy,” he added.
“Instead of giving an immunotherapy with little chance of success, patients and families deserve to have a direct conversation about what realistic expectations [might be] and how we as the oncology community can support them to achieve whatever their personal goals are in the time that they have left,” he emphasized.
Dr. Luke was the lead author of an editorial in which he commented on the study. Both the study and the editorial were published online in JCO Oncology Practice.
Variety of cancers
The study was conducted by Mridula Krishnan, MD, Nebraska Medicine Fred and Pamela Buffett Cancer Center, Omaha, Nebraska, and colleagues.
The team reviewed 257 patients who had been treated with either a programmed cell death protein–1 inhibitor or programmed cell death–ligand-1 inhibitor for a variety of advanced cancers. The drugs included pembrolizumab (Keytruda), nivolumab (Opdivo), atezolizumab (Tecentique), durvalumab (Imfinzi), and avelumab (Bavencio).
Most of the patients (71%) had good PS, with an Eastern Cooperative Oncology Group (ECOG) PS of 0-1 on initiation of immunotherapy; 29% of patients had poor PS, with an ECOG PS of greater than or equal to 2.
“The primary outcome was OS stratified by ECOG PS 0-1 versus ≥2,” note the authors. Across all tumor types, OS was superior for patients in the ECOG 0-1 PS group, the investigators note. The median OS was 12.6 months, compared with only 3.1 months for patients in the ECOG greater than or equal to 2 group (P < .001).
Moreover, overall response rates for patients with a poor PS were low. Only 8%, or 6 of 75 patients with an ECOG PS of greater than or equal to 2, achieved an objective response by RECIST criteria.
This compared to an overall response rate of 23% for patients with an ECOG PS of 0-1, the investigators note (P = .005).
Interestingly, the hospice referral rate for patients with a poor PS (67%) was similar to that of patients with a PS of 1-2 (61.9%), Dr. Krishnan and colleagues observe.
Those with a poor PS were more like to die in-hospital (28.6%) than were patients with a good PS (15.1%; P = .035). The authors point out that it is well known that outcomes with chemotherapy are worse among patients who experience a decline in functional reserve, owing to increased susceptibility to toxicity and complications.
“Regardless of age, patients with ECOG PS >2 usually have poor tolerability to chemotherapy, and this correlates with worse survival outcome,” they emphasize. There is as yet no clear guidance regarding the impact of PS on ICI treatment response, although “there should be,” Dr. Luke believes.
“In a patient with declining performance status, especially ECOG PS 3-4 but potentially 2 as well, there is little likelihood that the functional and immune reserve of the patient will be adequate to mount a robust antitumor response,” he elaborated.
“It’s not impossible, but trying for it should not come at the expense of engaging about end-of-life care and maximizing the palliative opportunities that many only have a short window of time in which to pursue,” he added.
Again, Dr. Luke strongly believes that just giving an ICI without engaging in a frank conversation with the patient and their families – which happens all too often, he feels – is absolutely not the way to go when treating patients with a poor PS and little time left.
“Patients and families might be better served by having a more direct and frank conversation about what the likelihood [is] that ICI therapy will actually do,” Dr. Luke stressed.
In their editorial, Dr. Luke and colleagues write: “Overall, we as an oncology community need to improve our communication with patients regarding goals of care and end-of-life considerations as opposed to reflexive treatment initiation,” he writes.
“Our duty, first and foremost, should focus on the person sitting in front of us – taking a step back may be the best way to move forward with compassionate care,” they add.
The authors and editorialists have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The findings have prompted an expert to argue against the use of immunotherapy for such patients, who may have little time left and very little chance of benefiting.
“It is quite clear from clinical practice that most patients with limited PS do very poorly and do not benefit from immune check point inhibitors (ICI),” Jason Luke, MD, UPMC Hillman Cancer Center and the University of Pittsburgh, said in an email.
“So, my strong opinion is that patients should not be getting an immunotherapy just because it might not cause as many side effects as chemotherapy,” he added.
“Instead of giving an immunotherapy with little chance of success, patients and families deserve to have a direct conversation about what realistic expectations [might be] and how we as the oncology community can support them to achieve whatever their personal goals are in the time that they have left,” he emphasized.
Dr. Luke was the lead author of an editorial in which he commented on the study. Both the study and the editorial were published online in JCO Oncology Practice.
Variety of cancers
The study was conducted by Mridula Krishnan, MD, Nebraska Medicine Fred and Pamela Buffett Cancer Center, Omaha, Nebraska, and colleagues.
The team reviewed 257 patients who had been treated with either a programmed cell death protein–1 inhibitor or programmed cell death–ligand-1 inhibitor for a variety of advanced cancers. The drugs included pembrolizumab (Keytruda), nivolumab (Opdivo), atezolizumab (Tecentique), durvalumab (Imfinzi), and avelumab (Bavencio).
Most of the patients (71%) had good PS, with an Eastern Cooperative Oncology Group (ECOG) PS of 0-1 on initiation of immunotherapy; 29% of patients had poor PS, with an ECOG PS of greater than or equal to 2.
“The primary outcome was OS stratified by ECOG PS 0-1 versus ≥2,” note the authors. Across all tumor types, OS was superior for patients in the ECOG 0-1 PS group, the investigators note. The median OS was 12.6 months, compared with only 3.1 months for patients in the ECOG greater than or equal to 2 group (P < .001).
Moreover, overall response rates for patients with a poor PS were low. Only 8%, or 6 of 75 patients with an ECOG PS of greater than or equal to 2, achieved an objective response by RECIST criteria.
This compared to an overall response rate of 23% for patients with an ECOG PS of 0-1, the investigators note (P = .005).
Interestingly, the hospice referral rate for patients with a poor PS (67%) was similar to that of patients with a PS of 1-2 (61.9%), Dr. Krishnan and colleagues observe.
Those with a poor PS were more like to die in-hospital (28.6%) than were patients with a good PS (15.1%; P = .035). The authors point out that it is well known that outcomes with chemotherapy are worse among patients who experience a decline in functional reserve, owing to increased susceptibility to toxicity and complications.
“Regardless of age, patients with ECOG PS >2 usually have poor tolerability to chemotherapy, and this correlates with worse survival outcome,” they emphasize. There is as yet no clear guidance regarding the impact of PS on ICI treatment response, although “there should be,” Dr. Luke believes.
“In a patient with declining performance status, especially ECOG PS 3-4 but potentially 2 as well, there is little likelihood that the functional and immune reserve of the patient will be adequate to mount a robust antitumor response,” he elaborated.
“It’s not impossible, but trying for it should not come at the expense of engaging about end-of-life care and maximizing the palliative opportunities that many only have a short window of time in which to pursue,” he added.
Again, Dr. Luke strongly believes that just giving an ICI without engaging in a frank conversation with the patient and their families – which happens all too often, he feels – is absolutely not the way to go when treating patients with a poor PS and little time left.
“Patients and families might be better served by having a more direct and frank conversation about what the likelihood [is] that ICI therapy will actually do,” Dr. Luke stressed.
In their editorial, Dr. Luke and colleagues write: “Overall, we as an oncology community need to improve our communication with patients regarding goals of care and end-of-life considerations as opposed to reflexive treatment initiation,” he writes.
“Our duty, first and foremost, should focus on the person sitting in front of us – taking a step back may be the best way to move forward with compassionate care,” they add.
The authors and editorialists have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Transfusions, readmissions higher for patients with CLL after cardiac surgery
Patients with chronic lymphocytic leukemia have similar outcomes following cardiac operations as patients without CLL, but commonly require more blood transfusions, according to the results of retrospective cohort study using the 2010-2017 Nationwide Readmissions Database (NRD).
The researchers assessed all adult patients undergoing elective coronary artery bypass grafting, valve repair, or valve replacement as identified using the NRD.
Patients were stratified by history of CLL and the incidence of in-hospital mortality, perioperative complications, blood transfusions, and readmission within 90 days were examined. A 3:1 nearest-neighbor matching was performed between patients with and without CLL for all primary and secondary outcomes of interest, according to the report, published online in Annals of Thoracic Surgery.
Comparable results
A total of 1,250,882 patients in the database were found who underwent cardiac operations. Of these, 0.23% had a diagnosis of CLL. Among 11,237 propensity-matched patients, those with CLL had similar rates of in-hospital mortality (3.8% vs. 2.6%, P = .08) and perioperative complications (33.4% vs. 33.6%, P = .92), compared with their non-CLL counterparts. However, the incidence of infection was comparable (8.5% vs. 9.4%, P = .38).
However, patients with CLL required blood transfusions more frequently (33.7% vs. 28.4%, P = .003) than did patients without CLL. In addition, patients with CLL were more likely to be readmitted within 90 days of discharge, compared with their counterparts, and “respiratory reasons, including pneumonia, contributed significantly to the readmission burden in this cohort,” the researchers, led by Josef Madrigal, BS, of the University of California, Los Angeles, stated.
“The inherent risk of transfusion and the possible benefits of blood conservation interventions must be considered in this patient population. Increased risk of rehospitalization in patients with CLL suggests the need for measures aimed at mitigating the risk of respiratory complications,” the researchers concluded.
There were no conflicts of interest reported in the article.
Patients with chronic lymphocytic leukemia have similar outcomes following cardiac operations as patients without CLL, but commonly require more blood transfusions, according to the results of retrospective cohort study using the 2010-2017 Nationwide Readmissions Database (NRD).
The researchers assessed all adult patients undergoing elective coronary artery bypass grafting, valve repair, or valve replacement as identified using the NRD.
Patients were stratified by history of CLL and the incidence of in-hospital mortality, perioperative complications, blood transfusions, and readmission within 90 days were examined. A 3:1 nearest-neighbor matching was performed between patients with and without CLL for all primary and secondary outcomes of interest, according to the report, published online in Annals of Thoracic Surgery.
Comparable results
A total of 1,250,882 patients in the database were found who underwent cardiac operations. Of these, 0.23% had a diagnosis of CLL. Among 11,237 propensity-matched patients, those with CLL had similar rates of in-hospital mortality (3.8% vs. 2.6%, P = .08) and perioperative complications (33.4% vs. 33.6%, P = .92), compared with their non-CLL counterparts. However, the incidence of infection was comparable (8.5% vs. 9.4%, P = .38).
However, patients with CLL required blood transfusions more frequently (33.7% vs. 28.4%, P = .003) than did patients without CLL. In addition, patients with CLL were more likely to be readmitted within 90 days of discharge, compared with their counterparts, and “respiratory reasons, including pneumonia, contributed significantly to the readmission burden in this cohort,” the researchers, led by Josef Madrigal, BS, of the University of California, Los Angeles, stated.
“The inherent risk of transfusion and the possible benefits of blood conservation interventions must be considered in this patient population. Increased risk of rehospitalization in patients with CLL suggests the need for measures aimed at mitigating the risk of respiratory complications,” the researchers concluded.
There were no conflicts of interest reported in the article.
Patients with chronic lymphocytic leukemia have similar outcomes following cardiac operations as patients without CLL, but commonly require more blood transfusions, according to the results of retrospective cohort study using the 2010-2017 Nationwide Readmissions Database (NRD).
The researchers assessed all adult patients undergoing elective coronary artery bypass grafting, valve repair, or valve replacement as identified using the NRD.
Patients were stratified by history of CLL and the incidence of in-hospital mortality, perioperative complications, blood transfusions, and readmission within 90 days were examined. A 3:1 nearest-neighbor matching was performed between patients with and without CLL for all primary and secondary outcomes of interest, according to the report, published online in Annals of Thoracic Surgery.
Comparable results
A total of 1,250,882 patients in the database were found who underwent cardiac operations. Of these, 0.23% had a diagnosis of CLL. Among 11,237 propensity-matched patients, those with CLL had similar rates of in-hospital mortality (3.8% vs. 2.6%, P = .08) and perioperative complications (33.4% vs. 33.6%, P = .92), compared with their non-CLL counterparts. However, the incidence of infection was comparable (8.5% vs. 9.4%, P = .38).
However, patients with CLL required blood transfusions more frequently (33.7% vs. 28.4%, P = .003) than did patients without CLL. In addition, patients with CLL were more likely to be readmitted within 90 days of discharge, compared with their counterparts, and “respiratory reasons, including pneumonia, contributed significantly to the readmission burden in this cohort,” the researchers, led by Josef Madrigal, BS, of the University of California, Los Angeles, stated.
“The inherent risk of transfusion and the possible benefits of blood conservation interventions must be considered in this patient population. Increased risk of rehospitalization in patients with CLL suggests the need for measures aimed at mitigating the risk of respiratory complications,” the researchers concluded.
There were no conflicts of interest reported in the article.
FROM THE ANNALS OF THORACIC SURGERY
‘New first-line standard of care’ in cervical cancer
That declaration was made by Raza Mirza, MD, chief oncologist at Copenhagen University Hospital in Denmark, who was invited to discuss the pros and cons of the KEYNOTE-826 trial at the European Society for Medical Oncology (ESMO) Congress 2021.
The trial showed that adding the checkpoint inhibitor pembrolizumab (Keytruda) to standard chemotherapy — with or without bevacizumab — resulted in about a one third reduction in the risk for both disease progression and death compared with chemotherapy alone.
The benefit of adding pembrolizumab was seen both in the overall study population and in patients with higher levels of programmed death ligand-1 (PD-L1), but not in those with biomarker-negative tumors, reported investigator Nicoletta Colombo, MD, PhD, from the University of Milan-Bicocca, Italy.
“Overall, data from KEYNOTE-826 suggest that pembrolizumab plus platinum-based chemotherapy with or without bevacizumab may be a new first-line standard of care,” she said in a late-breaking oral abstract presentation. The study was also simultaneously published online in The New England Journal of Medicine.
Since 2014, the standard of care for treating patients with recurrent, persistent, or metastatic cervical cancer has been chemotherapy with a platinum compound, paclitaxel, plus bevacizumab, based on the results of the GOG 240 study.
Immunotherapy with PD-1 inhibitors have shown efficacy as monotherapy in second- or later-line therapy for women with cervical cancer, but until now no data about the addition of these agents to chemotherapy were available, Dr. Colombo noted.
Dr. Mirza noted that there is sound rationale for using checkpoint inhibitors targeted against PD-1 in patients with cervical cancer, because PD-L1 has been shown to be a consistent biomarker for infection of the cervix with human papillomavirus (HPV), which is responsible for more than 90% of cervical cancers.
“PD-L1 is significantly upregulated in cervical cancer and detectable by immunohistochemistry,” he said. “PD-L1 expression reduces the immune response since it is able to bind to PD-1 on T-cell lymphocytes, thereby inhibiting their function. These findings suggest that targeting the PD-1/PD-L1 pathway may be therapeutically effective and should be considered in the treatment of cervical cancer.”
KEYNOTE-826 details
This was a double-blind trial conducted in 617 patients stratified by metastatic disease status at diagnosis; PD-L1 combined positive score (CPS) either < 1, 1 to < 10, or ≥ 10. They were randomized in a 1:1 ratio to receive pembrolizumab 200 mg or placebo every 3 weeks for up to 35 cycles plus platinum-based chemotherapy, with bevacizumab added at the investigator’s discretion.
The dual primary endpoints of progression-free survival (PFS) and overall survival (OS) were each tested sequentially in patients with a PD-L1 CPS ≥ 1 in both the intention-to-treat (ITT) or “all-comers” population, and in patients with a PD-L1 CPS ≥ 10.
Patient characteristics were generally well balanced between the treatment groups, except for a slightly higher proportion of patients with squamous cell histology in the pembrolizumab versus the placebo group (76.3% vs 68.3%).
PFS and OS results
The addition of pembrolizumab was associated with improved PFS across most protocol-specified subgroups, Dr. Colombo and colleagues noted.
After a median follow-up of 22 months, the 12-month PFS rate in the biomarker-selected population (all patients with a PD-L1 CPS ≥ 1) was 45.5% for patients in the pembrolizumab group versus 34.1% in the placebo group. This translated into a hazard ratio (HR) for progression on pembrolizumab of 0.62 (P < .001).
The respective PFS rates in the ITT population were 44.7% and 33.5%, with an HR for progression of 0.65 (P < .001) with the checkpoint inhibitor.
In patients with PD-L1 CPS ≥ 10, the respective rates of PFS and the HR were 44.6%, 33.5%, and 0.58 (P < .001).
OS rates were also significantly improved, he noted.
The 12-month and 24-month OS rates in all patients with PD-L1 CPS ≥ 1 were 75.3% and 53%, respectively, for patients assigned to pembrolizumab versus 63.1% and 41.7% in patients assigned to placebo, translating to an HR for death with pembrolizumab in this group of 0.64 (P < .001).
In the all-comers (ITT) population, respective 12- and 24-month OS rates were 74.8% and 50.4% with pembrolizumab versus 63.6% and 40.4% with placebo. This difference translated into an HR for death with anti-PD-1 of 0.67 (P < .001).
Among patients with the higher PD-L1 levels (≥ CPS 10), the respective OS rates were 75.7% and 54.4% with pembrolizumab versus 61.5% and 44.6% with placebo (HR 0.61, P < .001).
Dr. Mirza emphasized that “we did not see any efficacy of pembrolizumab in the biomarker-negative population,” with an HR for PFS of 0.94 and HR for OS of 1.0 in this subgroup.
The most common grade ≥ 3 adverse events were anemia, which occurred in 30.3% of patients assigned to pembrolizumab compared with 26.9% in the placebo group, and neutropenias, which occurred in 12.4% and 9.7% of patients, respectively. One patient in the pembrolizumab group died from an immune-related event, encephalitis.
Despite his enthusiasm for the regimen, Dr. Mirza tempered it by pointing out that there was an imbalance in the sample sizes regarding histology, and a potential bias introduced by the failure to stratify by tumor histology.
He noted that in other studies checkpoint inhibitors have had only modest activity against adenocarcinomas, which were more frequent in the placebo group in KEYNOTE-826, resulting in a potential positive bias in favor of pembrolizumab.
KEYNOTE-826 is funded by MSD. Dr. Colombo has disclosed consultant, research, and promotional speaking activities for multiple companies. Dr. Mirza has disclosed personal financial interests with Merck and other companies.
A version of this article was first published on Medscape.com.
That declaration was made by Raza Mirza, MD, chief oncologist at Copenhagen University Hospital in Denmark, who was invited to discuss the pros and cons of the KEYNOTE-826 trial at the European Society for Medical Oncology (ESMO) Congress 2021.
The trial showed that adding the checkpoint inhibitor pembrolizumab (Keytruda) to standard chemotherapy — with or without bevacizumab — resulted in about a one third reduction in the risk for both disease progression and death compared with chemotherapy alone.
The benefit of adding pembrolizumab was seen both in the overall study population and in patients with higher levels of programmed death ligand-1 (PD-L1), but not in those with biomarker-negative tumors, reported investigator Nicoletta Colombo, MD, PhD, from the University of Milan-Bicocca, Italy.
“Overall, data from KEYNOTE-826 suggest that pembrolizumab plus platinum-based chemotherapy with or without bevacizumab may be a new first-line standard of care,” she said in a late-breaking oral abstract presentation. The study was also simultaneously published online in The New England Journal of Medicine.
Since 2014, the standard of care for treating patients with recurrent, persistent, or metastatic cervical cancer has been chemotherapy with a platinum compound, paclitaxel, plus bevacizumab, based on the results of the GOG 240 study.
Immunotherapy with PD-1 inhibitors have shown efficacy as monotherapy in second- or later-line therapy for women with cervical cancer, but until now no data about the addition of these agents to chemotherapy were available, Dr. Colombo noted.
Dr. Mirza noted that there is sound rationale for using checkpoint inhibitors targeted against PD-1 in patients with cervical cancer, because PD-L1 has been shown to be a consistent biomarker for infection of the cervix with human papillomavirus (HPV), which is responsible for more than 90% of cervical cancers.
“PD-L1 is significantly upregulated in cervical cancer and detectable by immunohistochemistry,” he said. “PD-L1 expression reduces the immune response since it is able to bind to PD-1 on T-cell lymphocytes, thereby inhibiting their function. These findings suggest that targeting the PD-1/PD-L1 pathway may be therapeutically effective and should be considered in the treatment of cervical cancer.”
KEYNOTE-826 details
This was a double-blind trial conducted in 617 patients stratified by metastatic disease status at diagnosis; PD-L1 combined positive score (CPS) either < 1, 1 to < 10, or ≥ 10. They were randomized in a 1:1 ratio to receive pembrolizumab 200 mg or placebo every 3 weeks for up to 35 cycles plus platinum-based chemotherapy, with bevacizumab added at the investigator’s discretion.
The dual primary endpoints of progression-free survival (PFS) and overall survival (OS) were each tested sequentially in patients with a PD-L1 CPS ≥ 1 in both the intention-to-treat (ITT) or “all-comers” population, and in patients with a PD-L1 CPS ≥ 10.
Patient characteristics were generally well balanced between the treatment groups, except for a slightly higher proportion of patients with squamous cell histology in the pembrolizumab versus the placebo group (76.3% vs 68.3%).
PFS and OS results
The addition of pembrolizumab was associated with improved PFS across most protocol-specified subgroups, Dr. Colombo and colleagues noted.
After a median follow-up of 22 months, the 12-month PFS rate in the biomarker-selected population (all patients with a PD-L1 CPS ≥ 1) was 45.5% for patients in the pembrolizumab group versus 34.1% in the placebo group. This translated into a hazard ratio (HR) for progression on pembrolizumab of 0.62 (P < .001).
The respective PFS rates in the ITT population were 44.7% and 33.5%, with an HR for progression of 0.65 (P < .001) with the checkpoint inhibitor.
In patients with PD-L1 CPS ≥ 10, the respective rates of PFS and the HR were 44.6%, 33.5%, and 0.58 (P < .001).
OS rates were also significantly improved, he noted.
The 12-month and 24-month OS rates in all patients with PD-L1 CPS ≥ 1 were 75.3% and 53%, respectively, for patients assigned to pembrolizumab versus 63.1% and 41.7% in patients assigned to placebo, translating to an HR for death with pembrolizumab in this group of 0.64 (P < .001).
In the all-comers (ITT) population, respective 12- and 24-month OS rates were 74.8% and 50.4% with pembrolizumab versus 63.6% and 40.4% with placebo. This difference translated into an HR for death with anti-PD-1 of 0.67 (P < .001).
Among patients with the higher PD-L1 levels (≥ CPS 10), the respective OS rates were 75.7% and 54.4% with pembrolizumab versus 61.5% and 44.6% with placebo (HR 0.61, P < .001).
Dr. Mirza emphasized that “we did not see any efficacy of pembrolizumab in the biomarker-negative population,” with an HR for PFS of 0.94 and HR for OS of 1.0 in this subgroup.
The most common grade ≥ 3 adverse events were anemia, which occurred in 30.3% of patients assigned to pembrolizumab compared with 26.9% in the placebo group, and neutropenias, which occurred in 12.4% and 9.7% of patients, respectively. One patient in the pembrolizumab group died from an immune-related event, encephalitis.
Despite his enthusiasm for the regimen, Dr. Mirza tempered it by pointing out that there was an imbalance in the sample sizes regarding histology, and a potential bias introduced by the failure to stratify by tumor histology.
He noted that in other studies checkpoint inhibitors have had only modest activity against adenocarcinomas, which were more frequent in the placebo group in KEYNOTE-826, resulting in a potential positive bias in favor of pembrolizumab.
KEYNOTE-826 is funded by MSD. Dr. Colombo has disclosed consultant, research, and promotional speaking activities for multiple companies. Dr. Mirza has disclosed personal financial interests with Merck and other companies.
A version of this article was first published on Medscape.com.
That declaration was made by Raza Mirza, MD, chief oncologist at Copenhagen University Hospital in Denmark, who was invited to discuss the pros and cons of the KEYNOTE-826 trial at the European Society for Medical Oncology (ESMO) Congress 2021.
The trial showed that adding the checkpoint inhibitor pembrolizumab (Keytruda) to standard chemotherapy — with or without bevacizumab — resulted in about a one third reduction in the risk for both disease progression and death compared with chemotherapy alone.
The benefit of adding pembrolizumab was seen both in the overall study population and in patients with higher levels of programmed death ligand-1 (PD-L1), but not in those with biomarker-negative tumors, reported investigator Nicoletta Colombo, MD, PhD, from the University of Milan-Bicocca, Italy.
“Overall, data from KEYNOTE-826 suggest that pembrolizumab plus platinum-based chemotherapy with or without bevacizumab may be a new first-line standard of care,” she said in a late-breaking oral abstract presentation. The study was also simultaneously published online in The New England Journal of Medicine.
Since 2014, the standard of care for treating patients with recurrent, persistent, or metastatic cervical cancer has been chemotherapy with a platinum compound, paclitaxel, plus bevacizumab, based on the results of the GOG 240 study.
Immunotherapy with PD-1 inhibitors have shown efficacy as monotherapy in second- or later-line therapy for women with cervical cancer, but until now no data about the addition of these agents to chemotherapy were available, Dr. Colombo noted.
Dr. Mirza noted that there is sound rationale for using checkpoint inhibitors targeted against PD-1 in patients with cervical cancer, because PD-L1 has been shown to be a consistent biomarker for infection of the cervix with human papillomavirus (HPV), which is responsible for more than 90% of cervical cancers.
“PD-L1 is significantly upregulated in cervical cancer and detectable by immunohistochemistry,” he said. “PD-L1 expression reduces the immune response since it is able to bind to PD-1 on T-cell lymphocytes, thereby inhibiting their function. These findings suggest that targeting the PD-1/PD-L1 pathway may be therapeutically effective and should be considered in the treatment of cervical cancer.”
KEYNOTE-826 details
This was a double-blind trial conducted in 617 patients stratified by metastatic disease status at diagnosis; PD-L1 combined positive score (CPS) either < 1, 1 to < 10, or ≥ 10. They were randomized in a 1:1 ratio to receive pembrolizumab 200 mg or placebo every 3 weeks for up to 35 cycles plus platinum-based chemotherapy, with bevacizumab added at the investigator’s discretion.
The dual primary endpoints of progression-free survival (PFS) and overall survival (OS) were each tested sequentially in patients with a PD-L1 CPS ≥ 1 in both the intention-to-treat (ITT) or “all-comers” population, and in patients with a PD-L1 CPS ≥ 10.
Patient characteristics were generally well balanced between the treatment groups, except for a slightly higher proportion of patients with squamous cell histology in the pembrolizumab versus the placebo group (76.3% vs 68.3%).
PFS and OS results
The addition of pembrolizumab was associated with improved PFS across most protocol-specified subgroups, Dr. Colombo and colleagues noted.
After a median follow-up of 22 months, the 12-month PFS rate in the biomarker-selected population (all patients with a PD-L1 CPS ≥ 1) was 45.5% for patients in the pembrolizumab group versus 34.1% in the placebo group. This translated into a hazard ratio (HR) for progression on pembrolizumab of 0.62 (P < .001).
The respective PFS rates in the ITT population were 44.7% and 33.5%, with an HR for progression of 0.65 (P < .001) with the checkpoint inhibitor.
In patients with PD-L1 CPS ≥ 10, the respective rates of PFS and the HR were 44.6%, 33.5%, and 0.58 (P < .001).
OS rates were also significantly improved, he noted.
The 12-month and 24-month OS rates in all patients with PD-L1 CPS ≥ 1 were 75.3% and 53%, respectively, for patients assigned to pembrolizumab versus 63.1% and 41.7% in patients assigned to placebo, translating to an HR for death with pembrolizumab in this group of 0.64 (P < .001).
In the all-comers (ITT) population, respective 12- and 24-month OS rates were 74.8% and 50.4% with pembrolizumab versus 63.6% and 40.4% with placebo. This difference translated into an HR for death with anti-PD-1 of 0.67 (P < .001).
Among patients with the higher PD-L1 levels (≥ CPS 10), the respective OS rates were 75.7% and 54.4% with pembrolizumab versus 61.5% and 44.6% with placebo (HR 0.61, P < .001).
Dr. Mirza emphasized that “we did not see any efficacy of pembrolizumab in the biomarker-negative population,” with an HR for PFS of 0.94 and HR for OS of 1.0 in this subgroup.
The most common grade ≥ 3 adverse events were anemia, which occurred in 30.3% of patients assigned to pembrolizumab compared with 26.9% in the placebo group, and neutropenias, which occurred in 12.4% and 9.7% of patients, respectively. One patient in the pembrolizumab group died from an immune-related event, encephalitis.
Despite his enthusiasm for the regimen, Dr. Mirza tempered it by pointing out that there was an imbalance in the sample sizes regarding histology, and a potential bias introduced by the failure to stratify by tumor histology.
He noted that in other studies checkpoint inhibitors have had only modest activity against adenocarcinomas, which were more frequent in the placebo group in KEYNOTE-826, resulting in a potential positive bias in favor of pembrolizumab.
KEYNOTE-826 is funded by MSD. Dr. Colombo has disclosed consultant, research, and promotional speaking activities for multiple companies. Dr. Mirza has disclosed personal financial interests with Merck and other companies.
A version of this article was first published on Medscape.com.
Assessing headache severity via migraine symptoms can help predict outcomes
according to an analysis of data from thousands of headache sufferers who recorded variables like pain and duration in a daily digital diary.
“Our hope is that this work serves as foundational basis for better understanding the complexity of headache as a symptom-based condition,” James S. McGinley, PhD, of Vector Psychometric Group in Chapel Hill, N.C., and coauthors wrote. The study was published in Cephalalgia.
To evaluate whether keeping track of daily headache features can produce a useful, predictive score, the researchers reviewed data from migraine patients that were collected via N1‑Headache, a commercial digital health platform. Ultimately, information from 4,380 adults with a self-reported migraine diagnosis was analyzed; the sample was 90% female and their mean age was 37 years. Study participants reported an average of 33 headaches per month over the last 3 months. Nine patient-reported variables were initially considered in calculating the Headache Day Severity (HDS) score: pain intensity, headache duration, aura, pulsating/throbbing pain, unilateral pain, pain aggravation by activity, nausea/vomiting, photophobia, and phonophobia.
After determining that unilateral pain was not a meaningful variable, the researchers’ model found that, for every 1 standard deviation increase in HDS, the patient’s odds of physician visit increased by 71% (odds ratio, 1.71; 95% confidence interval, 1.32-2.21) and the odds of an ED visit increased by 342% (OR, 4.42; 95% CI, 2.23-7.60). They also found that the likelihood of missed work or school increased by 190% (OR, 2.90; 95% CI, 2.56-3.29), the chances of missing household work increased by 237% (OR, 3.37; 95% CI, 3.06-3.72) and the odds of missing other leisure or social activity increased by 228% (OR, 3.28; 95% CI, 2.97-3.64).
Tracking multiple variables
“We encourage all of our patients to monitor their headaches; there are just too many variables to try to keep it in your head,” Robert Cowan, MD, professor of neurology and chief of the division of headache medicine at Stanford (Calif.) University, said in an interview. He referenced a previous study from the University of Washington where patients were asked to track their headaches; that data was then compared against their self-reported headaches at a quarterly physician visit.
“What they found was there was absolutely no correlation with reported frequency of headache at the visit and what was seen in the tracker,” he said. “If patients had a headache in the previous 3 days before their visit, they felt that their headaches were poorly controlled. If they hadn’t, they thought their headaches were under good control. So the value of tracking is pretty clear.”
He added that, while not every headache sufferer needs to track their daily routines and symptoms, once those symptoms interfere with your life on a day-to-day basis, it’s probably time to consider keeping tabs on yourself with a tool of some sort. And while this study’s calculated HDS score supports the idea of migraine’s complexity, it also leaves unanswered the question of how to treat patients with severe symptoms.
“Frequently,” he said, “we’ll see patients who say: ‘I can deal with the pain, but the nausea makes it impossible to work, or the light sensitivity makes it impossible to go outside.’ The big question within the headache community is, can you treat migraine and have it address the whole spectrum, from dizziness to light sensitivity to sound sensitivity to vertigo, or should you be going after individual symptoms? That’s a controversy that rages on; I think most of us go for a combination. We’re in a polypharmacy phase: ‘If nausea is a big problem, take this, but we also try to prevent the whole migraine complex, so take this as well.’ ”
The authors acknowledged their study’s limitations, including the inability to determine how many participants’ migraines were formally diagnosed by a trained medical professional and the lack of generalizability of data from a convenience sample, though they added that patients who independently track their own headaches “may be representative of those who would participate in a clinical trial.” In addition, as seven of the nine features were collected in N1‑Headache on a yes/no scale, they recognized that “increasing the number of response options for each item may improve our ability to measure HDS.”
The study was funded by Amgen through the Competitive Grant Program in Migraine Research. The authors declared several potential conflicts of interest, including receiving funding, research support, salary, and honoraria from various pharmaceutical companies.
according to an analysis of data from thousands of headache sufferers who recorded variables like pain and duration in a daily digital diary.
“Our hope is that this work serves as foundational basis for better understanding the complexity of headache as a symptom-based condition,” James S. McGinley, PhD, of Vector Psychometric Group in Chapel Hill, N.C., and coauthors wrote. The study was published in Cephalalgia.
To evaluate whether keeping track of daily headache features can produce a useful, predictive score, the researchers reviewed data from migraine patients that were collected via N1‑Headache, a commercial digital health platform. Ultimately, information from 4,380 adults with a self-reported migraine diagnosis was analyzed; the sample was 90% female and their mean age was 37 years. Study participants reported an average of 33 headaches per month over the last 3 months. Nine patient-reported variables were initially considered in calculating the Headache Day Severity (HDS) score: pain intensity, headache duration, aura, pulsating/throbbing pain, unilateral pain, pain aggravation by activity, nausea/vomiting, photophobia, and phonophobia.
After determining that unilateral pain was not a meaningful variable, the researchers’ model found that, for every 1 standard deviation increase in HDS, the patient’s odds of physician visit increased by 71% (odds ratio, 1.71; 95% confidence interval, 1.32-2.21) and the odds of an ED visit increased by 342% (OR, 4.42; 95% CI, 2.23-7.60). They also found that the likelihood of missed work or school increased by 190% (OR, 2.90; 95% CI, 2.56-3.29), the chances of missing household work increased by 237% (OR, 3.37; 95% CI, 3.06-3.72) and the odds of missing other leisure or social activity increased by 228% (OR, 3.28; 95% CI, 2.97-3.64).
Tracking multiple variables
“We encourage all of our patients to monitor their headaches; there are just too many variables to try to keep it in your head,” Robert Cowan, MD, professor of neurology and chief of the division of headache medicine at Stanford (Calif.) University, said in an interview. He referenced a previous study from the University of Washington where patients were asked to track their headaches; that data was then compared against their self-reported headaches at a quarterly physician visit.
“What they found was there was absolutely no correlation with reported frequency of headache at the visit and what was seen in the tracker,” he said. “If patients had a headache in the previous 3 days before their visit, they felt that their headaches were poorly controlled. If they hadn’t, they thought their headaches were under good control. So the value of tracking is pretty clear.”
He added that, while not every headache sufferer needs to track their daily routines and symptoms, once those symptoms interfere with your life on a day-to-day basis, it’s probably time to consider keeping tabs on yourself with a tool of some sort. And while this study’s calculated HDS score supports the idea of migraine’s complexity, it also leaves unanswered the question of how to treat patients with severe symptoms.
“Frequently,” he said, “we’ll see patients who say: ‘I can deal with the pain, but the nausea makes it impossible to work, or the light sensitivity makes it impossible to go outside.’ The big question within the headache community is, can you treat migraine and have it address the whole spectrum, from dizziness to light sensitivity to sound sensitivity to vertigo, or should you be going after individual symptoms? That’s a controversy that rages on; I think most of us go for a combination. We’re in a polypharmacy phase: ‘If nausea is a big problem, take this, but we also try to prevent the whole migraine complex, so take this as well.’ ”
The authors acknowledged their study’s limitations, including the inability to determine how many participants’ migraines were formally diagnosed by a trained medical professional and the lack of generalizability of data from a convenience sample, though they added that patients who independently track their own headaches “may be representative of those who would participate in a clinical trial.” In addition, as seven of the nine features were collected in N1‑Headache on a yes/no scale, they recognized that “increasing the number of response options for each item may improve our ability to measure HDS.”
The study was funded by Amgen through the Competitive Grant Program in Migraine Research. The authors declared several potential conflicts of interest, including receiving funding, research support, salary, and honoraria from various pharmaceutical companies.
according to an analysis of data from thousands of headache sufferers who recorded variables like pain and duration in a daily digital diary.
“Our hope is that this work serves as foundational basis for better understanding the complexity of headache as a symptom-based condition,” James S. McGinley, PhD, of Vector Psychometric Group in Chapel Hill, N.C., and coauthors wrote. The study was published in Cephalalgia.
To evaluate whether keeping track of daily headache features can produce a useful, predictive score, the researchers reviewed data from migraine patients that were collected via N1‑Headache, a commercial digital health platform. Ultimately, information from 4,380 adults with a self-reported migraine diagnosis was analyzed; the sample was 90% female and their mean age was 37 years. Study participants reported an average of 33 headaches per month over the last 3 months. Nine patient-reported variables were initially considered in calculating the Headache Day Severity (HDS) score: pain intensity, headache duration, aura, pulsating/throbbing pain, unilateral pain, pain aggravation by activity, nausea/vomiting, photophobia, and phonophobia.
After determining that unilateral pain was not a meaningful variable, the researchers’ model found that, for every 1 standard deviation increase in HDS, the patient’s odds of physician visit increased by 71% (odds ratio, 1.71; 95% confidence interval, 1.32-2.21) and the odds of an ED visit increased by 342% (OR, 4.42; 95% CI, 2.23-7.60). They also found that the likelihood of missed work or school increased by 190% (OR, 2.90; 95% CI, 2.56-3.29), the chances of missing household work increased by 237% (OR, 3.37; 95% CI, 3.06-3.72) and the odds of missing other leisure or social activity increased by 228% (OR, 3.28; 95% CI, 2.97-3.64).
Tracking multiple variables
“We encourage all of our patients to monitor their headaches; there are just too many variables to try to keep it in your head,” Robert Cowan, MD, professor of neurology and chief of the division of headache medicine at Stanford (Calif.) University, said in an interview. He referenced a previous study from the University of Washington where patients were asked to track their headaches; that data was then compared against their self-reported headaches at a quarterly physician visit.
“What they found was there was absolutely no correlation with reported frequency of headache at the visit and what was seen in the tracker,” he said. “If patients had a headache in the previous 3 days before their visit, they felt that their headaches were poorly controlled. If they hadn’t, they thought their headaches were under good control. So the value of tracking is pretty clear.”
He added that, while not every headache sufferer needs to track their daily routines and symptoms, once those symptoms interfere with your life on a day-to-day basis, it’s probably time to consider keeping tabs on yourself with a tool of some sort. And while this study’s calculated HDS score supports the idea of migraine’s complexity, it also leaves unanswered the question of how to treat patients with severe symptoms.
“Frequently,” he said, “we’ll see patients who say: ‘I can deal with the pain, but the nausea makes it impossible to work, or the light sensitivity makes it impossible to go outside.’ The big question within the headache community is, can you treat migraine and have it address the whole spectrum, from dizziness to light sensitivity to sound sensitivity to vertigo, or should you be going after individual symptoms? That’s a controversy that rages on; I think most of us go for a combination. We’re in a polypharmacy phase: ‘If nausea is a big problem, take this, but we also try to prevent the whole migraine complex, so take this as well.’ ”
The authors acknowledged their study’s limitations, including the inability to determine how many participants’ migraines were formally diagnosed by a trained medical professional and the lack of generalizability of data from a convenience sample, though they added that patients who independently track their own headaches “may be representative of those who would participate in a clinical trial.” In addition, as seven of the nine features were collected in N1‑Headache on a yes/no scale, they recognized that “increasing the number of response options for each item may improve our ability to measure HDS.”
The study was funded by Amgen through the Competitive Grant Program in Migraine Research. The authors declared several potential conflicts of interest, including receiving funding, research support, salary, and honoraria from various pharmaceutical companies.
FROM CEPHALALGIA
FDA grants zanubrutinib an accelerated approval in marginal zone lymphoma
The U.S. Food and Drug Administration has granted an accelerated approval to zanubrutinib (Brukinsa) for the treatment of adult patients with relapsed or refractory (R/R) marginal zone lymphoma (MZL) who have received at least one anti-CD20–based regimen, the drug’s maker BeiGene announced in a press statement.
The drug works as an inhibitor of Bruton’s tyrosine kinase (BTK), which plays a critical role in B-cell–receptor signaling, a driver in the development of marginal zone lymphoma, according to the company.
The new approval comes just 2 weeks after the oral drug received an accelerated approval for the treatment of adult patients with Waldenström’s macroglobulinemia, a rare non-Hodgkin lymphoma. The drug also has an accelerated approval for treating mantle cell lymphoma in patients who have received at least one prior therapy and is being studied in the treatment of chronic lymphocytic leukemia.
The latest indication is based on results from two single-arm clinical trials, with overall response rate (ORR) as the primary endpoint.
In the multicenter, phase 2 MAGNOLIA trial, zanubrutinib “demonstrated impressive overall response and complete remission rates, with responses observed in all MZL subtypes,” said Stephen Opat, MBBS, of Monash University in Melbourne, lead principal investigator of the study. “In addition, this next-generation BTK inhibitor was well-tolerated in these patients, with low rate of discontinuation due to adverse reactions.”
In the MAGNOLIA trial, 66 patients with R/R MZL who had received at least one anti-CD20–based regimen were treated with zanubrutinib. Among the patients were 26 with extranodal subtype, 26 with nodal subtype, 12 with splenic subtype, and 4 with unknown subtype.
The ORR was 56% with a complete response rate of 20%, based on CT scan assessment.
In addition, the ORR was 67% with a complete response rate of 26%, based on PET-CT scan assessment.
The median duration of response (DoR) was not reached at the median follow-up time of 8.3 months, with 85% of responders still in remission at 12 months. Responses were observed in all MZL subtypes.
In an earlier, phase 1/2 trial of the agent, 20 patients were evaluated, including 9 with extranodal subtype, 5 with nodal subtype, and 6 with splenic subtype. Based on CT scan assessment, the ORR was 80% with a complete remission rate of 20%. The median DoR was not reached at the median follow-up time of 31.4 months, with 72% of responders still in remission at 12 months.
The most common (≥30%) adverse reactions, including laboratory abnormalities, in the pooled safety population of 847 patients were decreased neutrophil count, upper respiratory tract infection, decreased platelet count, hemorrhage, decreased lymphocyte count, rash, and musculoskeletal pain, said the company.
A version of this article first appeared on Medscape.com.
The U.S. Food and Drug Administration has granted an accelerated approval to zanubrutinib (Brukinsa) for the treatment of adult patients with relapsed or refractory (R/R) marginal zone lymphoma (MZL) who have received at least one anti-CD20–based regimen, the drug’s maker BeiGene announced in a press statement.
The drug works as an inhibitor of Bruton’s tyrosine kinase (BTK), which plays a critical role in B-cell–receptor signaling, a driver in the development of marginal zone lymphoma, according to the company.
The new approval comes just 2 weeks after the oral drug received an accelerated approval for the treatment of adult patients with Waldenström’s macroglobulinemia, a rare non-Hodgkin lymphoma. The drug also has an accelerated approval for treating mantle cell lymphoma in patients who have received at least one prior therapy and is being studied in the treatment of chronic lymphocytic leukemia.
The latest indication is based on results from two single-arm clinical trials, with overall response rate (ORR) as the primary endpoint.
In the multicenter, phase 2 MAGNOLIA trial, zanubrutinib “demonstrated impressive overall response and complete remission rates, with responses observed in all MZL subtypes,” said Stephen Opat, MBBS, of Monash University in Melbourne, lead principal investigator of the study. “In addition, this next-generation BTK inhibitor was well-tolerated in these patients, with low rate of discontinuation due to adverse reactions.”
In the MAGNOLIA trial, 66 patients with R/R MZL who had received at least one anti-CD20–based regimen were treated with zanubrutinib. Among the patients were 26 with extranodal subtype, 26 with nodal subtype, 12 with splenic subtype, and 4 with unknown subtype.
The ORR was 56% with a complete response rate of 20%, based on CT scan assessment.
In addition, the ORR was 67% with a complete response rate of 26%, based on PET-CT scan assessment.
The median duration of response (DoR) was not reached at the median follow-up time of 8.3 months, with 85% of responders still in remission at 12 months. Responses were observed in all MZL subtypes.
In an earlier, phase 1/2 trial of the agent, 20 patients were evaluated, including 9 with extranodal subtype, 5 with nodal subtype, and 6 with splenic subtype. Based on CT scan assessment, the ORR was 80% with a complete remission rate of 20%. The median DoR was not reached at the median follow-up time of 31.4 months, with 72% of responders still in remission at 12 months.
The most common (≥30%) adverse reactions, including laboratory abnormalities, in the pooled safety population of 847 patients were decreased neutrophil count, upper respiratory tract infection, decreased platelet count, hemorrhage, decreased lymphocyte count, rash, and musculoskeletal pain, said the company.
A version of this article first appeared on Medscape.com.
The U.S. Food and Drug Administration has granted an accelerated approval to zanubrutinib (Brukinsa) for the treatment of adult patients with relapsed or refractory (R/R) marginal zone lymphoma (MZL) who have received at least one anti-CD20–based regimen, the drug’s maker BeiGene announced in a press statement.
The drug works as an inhibitor of Bruton’s tyrosine kinase (BTK), which plays a critical role in B-cell–receptor signaling, a driver in the development of marginal zone lymphoma, according to the company.
The new approval comes just 2 weeks after the oral drug received an accelerated approval for the treatment of adult patients with Waldenström’s macroglobulinemia, a rare non-Hodgkin lymphoma. The drug also has an accelerated approval for treating mantle cell lymphoma in patients who have received at least one prior therapy and is being studied in the treatment of chronic lymphocytic leukemia.
The latest indication is based on results from two single-arm clinical trials, with overall response rate (ORR) as the primary endpoint.
In the multicenter, phase 2 MAGNOLIA trial, zanubrutinib “demonstrated impressive overall response and complete remission rates, with responses observed in all MZL subtypes,” said Stephen Opat, MBBS, of Monash University in Melbourne, lead principal investigator of the study. “In addition, this next-generation BTK inhibitor was well-tolerated in these patients, with low rate of discontinuation due to adverse reactions.”
In the MAGNOLIA trial, 66 patients with R/R MZL who had received at least one anti-CD20–based regimen were treated with zanubrutinib. Among the patients were 26 with extranodal subtype, 26 with nodal subtype, 12 with splenic subtype, and 4 with unknown subtype.
The ORR was 56% with a complete response rate of 20%, based on CT scan assessment.
In addition, the ORR was 67% with a complete response rate of 26%, based on PET-CT scan assessment.
The median duration of response (DoR) was not reached at the median follow-up time of 8.3 months, with 85% of responders still in remission at 12 months. Responses were observed in all MZL subtypes.
In an earlier, phase 1/2 trial of the agent, 20 patients were evaluated, including 9 with extranodal subtype, 5 with nodal subtype, and 6 with splenic subtype. Based on CT scan assessment, the ORR was 80% with a complete remission rate of 20%. The median DoR was not reached at the median follow-up time of 31.4 months, with 72% of responders still in remission at 12 months.
The most common (≥30%) adverse reactions, including laboratory abnormalities, in the pooled safety population of 847 patients were decreased neutrophil count, upper respiratory tract infection, decreased platelet count, hemorrhage, decreased lymphocyte count, rash, and musculoskeletal pain, said the company.
A version of this article first appeared on Medscape.com.
ADHD a new risk factor for Alzheimer’s?
results from a large, multigenerational study show.
“The findings suggest there are common genetic and/or environmental contributions to the association between ADHD and dementia,” study investigator Zheng Chang, PhD, from the department of medical epidemiology and biostatistics at Karolinska Institute, Stockholm, said in a statement.
“There have been few studies previously on the link between ADHD and dementia, all with limited sample size,” Dr. Chang said in an interview.
“This is the first study to look at ADHD and dementia within extended families. It’s a large population-based study including over 2 million individuals and their over 5 million biological relatives,” he noted.
The study was published online Sept. 9, 2021, in the journal Alzheimer’s & Dementia.
Shared familial risk
The researchers identified roughly 2.1 million people born in Sweden between 1980 and 2001. Overall, 3.2% of the cohort had a diagnosis of ADHD.
Using national registries, they linked these individuals to more than 5 million of their biological relatives including parents, grandparents, uncles, and aunts and determined which of these relatives developed dementia over time.
In adjusted analyses, parents of individuals with ADHD had 34% higher risk for any dementia than parents of those without ADHD (hazard ratio, 1.34; 95% CI, 1.11-1.63).
The risk for AD, the most common type of dementia, was 55% higher in parents of individuals with ADHD (HR, 1.55; 95% CI, 1.26-1.89).
Individuals with ADHD were more likely to have parents with early-onset dementia rather than late-onset dementia. However, the absolute risk for dementia was low for the parent cohort: Only 0.17% of the parents were diagnosed with dementia during follow-up.
The association between ADHD and dementia was not as strong for second-degree relatives of individuals with ADHD. For example, grandparents of individuals with ADHD had a 10% increased risk for dementia, compared with grandparents of individuals without ADHD.
The finding of attenuated associations with decreasing genetic relatedness (parents > grandparents and uncles/aunts), points to shared familial risk between ADHD and AD, the researchers said.
There could be “undiscovered genetic variants that contribute to either traits or family-wide environmental risk factors, such as socioeconomic status, that may have an impact on the association,” Dr. Chang said in the news release.
“There are no direct clinical implications from this study, but research like this could lead to further research with goals for improved detection, prevention, and treatment,” he said in an interview.
More questions than answers
Heather Snyder, PhD, vice president of medical and scientific relations for the Alzheimer’s Association that the way different brain diseases are linked “is a question the Alzheimer’s Association is often asked, and it is a part of our funding portfolio to get that question answered.”
This study looking at ADHD and dementia is “intriguing,” Dr. Snyder said, “because, right now, there is limited information available. That said, this is an association study; it shows that two things are somehow connected. Because of how the study was conducted, it does not – and cannot – prove causation,” Dr. Snyder said. “But it is interesting all the same. More research is needed to uncover specifically why and how these two diseases are related. That might eventually give us insight into how to manage risk or even improve treatment.”
The study was supported by grants from the Swedish Council for Health, Working Life and Welfare, the Swedish Research Council, the Swedish Brain Foundation, the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie, the Fredrik & Ingrid Thurings Stiftelse, and the Karolinska Institutet Research Foundation. Dr. Chang and Dr. Snyder disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
results from a large, multigenerational study show.
“The findings suggest there are common genetic and/or environmental contributions to the association between ADHD and dementia,” study investigator Zheng Chang, PhD, from the department of medical epidemiology and biostatistics at Karolinska Institute, Stockholm, said in a statement.
“There have been few studies previously on the link between ADHD and dementia, all with limited sample size,” Dr. Chang said in an interview.
“This is the first study to look at ADHD and dementia within extended families. It’s a large population-based study including over 2 million individuals and their over 5 million biological relatives,” he noted.
The study was published online Sept. 9, 2021, in the journal Alzheimer’s & Dementia.
Shared familial risk
The researchers identified roughly 2.1 million people born in Sweden between 1980 and 2001. Overall, 3.2% of the cohort had a diagnosis of ADHD.
Using national registries, they linked these individuals to more than 5 million of their biological relatives including parents, grandparents, uncles, and aunts and determined which of these relatives developed dementia over time.
In adjusted analyses, parents of individuals with ADHD had 34% higher risk for any dementia than parents of those without ADHD (hazard ratio, 1.34; 95% CI, 1.11-1.63).
The risk for AD, the most common type of dementia, was 55% higher in parents of individuals with ADHD (HR, 1.55; 95% CI, 1.26-1.89).
Individuals with ADHD were more likely to have parents with early-onset dementia rather than late-onset dementia. However, the absolute risk for dementia was low for the parent cohort: Only 0.17% of the parents were diagnosed with dementia during follow-up.
The association between ADHD and dementia was not as strong for second-degree relatives of individuals with ADHD. For example, grandparents of individuals with ADHD had a 10% increased risk for dementia, compared with grandparents of individuals without ADHD.
The finding of attenuated associations with decreasing genetic relatedness (parents > grandparents and uncles/aunts), points to shared familial risk between ADHD and AD, the researchers said.
There could be “undiscovered genetic variants that contribute to either traits or family-wide environmental risk factors, such as socioeconomic status, that may have an impact on the association,” Dr. Chang said in the news release.
“There are no direct clinical implications from this study, but research like this could lead to further research with goals for improved detection, prevention, and treatment,” he said in an interview.
More questions than answers
Heather Snyder, PhD, vice president of medical and scientific relations for the Alzheimer’s Association that the way different brain diseases are linked “is a question the Alzheimer’s Association is often asked, and it is a part of our funding portfolio to get that question answered.”
This study looking at ADHD and dementia is “intriguing,” Dr. Snyder said, “because, right now, there is limited information available. That said, this is an association study; it shows that two things are somehow connected. Because of how the study was conducted, it does not – and cannot – prove causation,” Dr. Snyder said. “But it is interesting all the same. More research is needed to uncover specifically why and how these two diseases are related. That might eventually give us insight into how to manage risk or even improve treatment.”
The study was supported by grants from the Swedish Council for Health, Working Life and Welfare, the Swedish Research Council, the Swedish Brain Foundation, the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie, the Fredrik & Ingrid Thurings Stiftelse, and the Karolinska Institutet Research Foundation. Dr. Chang and Dr. Snyder disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
results from a large, multigenerational study show.
“The findings suggest there are common genetic and/or environmental contributions to the association between ADHD and dementia,” study investigator Zheng Chang, PhD, from the department of medical epidemiology and biostatistics at Karolinska Institute, Stockholm, said in a statement.
“There have been few studies previously on the link between ADHD and dementia, all with limited sample size,” Dr. Chang said in an interview.
“This is the first study to look at ADHD and dementia within extended families. It’s a large population-based study including over 2 million individuals and their over 5 million biological relatives,” he noted.
The study was published online Sept. 9, 2021, in the journal Alzheimer’s & Dementia.
Shared familial risk
The researchers identified roughly 2.1 million people born in Sweden between 1980 and 2001. Overall, 3.2% of the cohort had a diagnosis of ADHD.
Using national registries, they linked these individuals to more than 5 million of their biological relatives including parents, grandparents, uncles, and aunts and determined which of these relatives developed dementia over time.
In adjusted analyses, parents of individuals with ADHD had 34% higher risk for any dementia than parents of those without ADHD (hazard ratio, 1.34; 95% CI, 1.11-1.63).
The risk for AD, the most common type of dementia, was 55% higher in parents of individuals with ADHD (HR, 1.55; 95% CI, 1.26-1.89).
Individuals with ADHD were more likely to have parents with early-onset dementia rather than late-onset dementia. However, the absolute risk for dementia was low for the parent cohort: Only 0.17% of the parents were diagnosed with dementia during follow-up.
The association between ADHD and dementia was not as strong for second-degree relatives of individuals with ADHD. For example, grandparents of individuals with ADHD had a 10% increased risk for dementia, compared with grandparents of individuals without ADHD.
The finding of attenuated associations with decreasing genetic relatedness (parents > grandparents and uncles/aunts), points to shared familial risk between ADHD and AD, the researchers said.
There could be “undiscovered genetic variants that contribute to either traits or family-wide environmental risk factors, such as socioeconomic status, that may have an impact on the association,” Dr. Chang said in the news release.
“There are no direct clinical implications from this study, but research like this could lead to further research with goals for improved detection, prevention, and treatment,” he said in an interview.
More questions than answers
Heather Snyder, PhD, vice president of medical and scientific relations for the Alzheimer’s Association that the way different brain diseases are linked “is a question the Alzheimer’s Association is often asked, and it is a part of our funding portfolio to get that question answered.”
This study looking at ADHD and dementia is “intriguing,” Dr. Snyder said, “because, right now, there is limited information available. That said, this is an association study; it shows that two things are somehow connected. Because of how the study was conducted, it does not – and cannot – prove causation,” Dr. Snyder said. “But it is interesting all the same. More research is needed to uncover specifically why and how these two diseases are related. That might eventually give us insight into how to manage risk or even improve treatment.”
The study was supported by grants from the Swedish Council for Health, Working Life and Welfare, the Swedish Research Council, the Swedish Brain Foundation, the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie, the Fredrik & Ingrid Thurings Stiftelse, and the Karolinska Institutet Research Foundation. Dr. Chang and Dr. Snyder disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Lipid levels tied to ALS risk
, new research shows.
The study also linked a higher ratio of total cholesterol to HDL with an increased risk for ALS. These findings, investigators noted, point to potential future biomarkers in screening for ALS and perhaps an approach to reduce risk or delay onset of ALS in the longer term.
“They may help build a biochemical picture of what’s going on and who might be at risk of developing ALS in the near future, particularly in people with a genetic predisposition to ALS,” study investigator Alexander G. Thompson, DPhil, Medical Research Council clinician scientist, Nuffield Department of Clinical Neurosciences, University of Oxford, United Kingdom, said in an interview.
He emphasized that although the current observational study cannot show cause and effect, such a relationship may exist.
The study was published online September 13 in the Journal of Neurology, Neurosurgery and Psychiatry.
Registry data
ALS is a disorder of progressive degeneration of upper and lower motor neurons. Genetic variants account for fewer than 15% of cases. The factors that are associated with the greatest risk are unclear.
To investigate, the researchers used data from the UK Biobank, a prospective cohort study of persons aged 39-72 years. Participants underwent an initial assessment between March 2006 and October 2010 and were followed for a median of 11.9 years.
In addition to providing demographic and health information, participants provided blood samples for biochemical analysis. This included measurements of total cholesterol, HDL, low-density lipoprotein (LDL) cholesterol, triglycerides, apoA1, apolipoprotein B (apoB), A1c, and creatinine.
Researchers used diagnostic codes in inpatient health records and death certificate information to verify ALS diagnoses.
The analysis included data from 502,409 participants. The mean age of the participants was 58 years, and 54.4% were women. During follow-up, 343 participants were diagnosed with ALS, yielding a crude incidence of 5.85 per 100,000 per year (95% confidence interval, 5.25-6.51).
After controlling for sex and age, results showed that higher HDL (hazard ratio, 0.84; 95% CI, 0.73-0.96; P = .010) and higher apoA1 (HR, 0.83; 95% CI, 0.72-0.94, P = .005) were associated with a reduced risk for subsequent ALS.
A higher ratio of total cholesterol to HDL was associated with increased ALS risk.
A rise in neurofilaments and other markers of neuronal loss typically occur within about a year of ALS symptom onset. To ensure that they were capturing participants whose blood samples were taken before the onset of neurodegeneration, the researchers performed a secondary analysis that excluded ALS diagnoses within 5 years of the baseline study visit.
Results of the analysis were largely consistent with models incorporating all participants with regard to magnitude and direction of associations. In addition, the findings persisted in models that controlled for statin use, smoking, and vascular disease.
Mechanism unclear
To more closely examine lipid status prior to ALS diagnosis, the researchers performed a nested case-control analysis that involved matching each participant who developed ALS with 20 participants of similar age, sex, and time of enrollment who did not develop the disease.
Linear models showed that levels of LDL and apoB, which are closely correlated, decrease over time in those who developed ALS. This was not the case for HDL and apoA1. “This suggests LDL levels are going down, and we think it’s happening quite some time before symptoms start, even before neurodegeneration starts,” said Dr. Thompson.
How blood lipid levels correlate with ALS risk is unclear. Dr. Thompson noted that LDL is an oxidative stressor and can provoke inflammation, whereas HDL is an antioxidant that is involved in healing. However, given that LDL and HDL don’t cross into the brain in great amounts, “the lipid changes may be a reflection of something else going on that contributes to the risk of ALS,” he said.
More evidence of a causal relationship is needed before any clinical implications can be drawn, including the potential manipulation of lipid levels to prevent ALS, said Dr. Thompson. In addition, even were such a relationship to be established, altering lipid levels in a healthy individual who has no family history of ALS would be unlikely to alter risk.
Dr. Thompson added that among those with a genetic predisposition, lipid changes “may be a marker or clue that something’s going wrong in the nervous system and that ALS might be about to start. That would be the ideal time to treat people at risk of ALS with gene therapy.”
Metabolism gone awry
Commenting on the findings, Stephen Goutman, MD, director, Pranger ALS Clinic, associate professor of neurology, Neuromuscular Program, University of Michigan, Ann Arbor, called the study “very interesting.” Of particular note was a trend of decreasing LDL and apoB levels prior to an ALS diagnosis, said Dr. Goutman.
The results are in agreement with several studies that show an alteration in metabolism in individuals with ALS, he said. “These altered metabolic pathways may provide some signal that something has gone awry,” he commented.
He agreed that an “ultimate goal” is to identify factors or biomarkers that can be used to predict whether individuals will develop ALS and to enable intervention to decrease the risk.
This new research highlights the value of population-based registries and large prospective cohorts, said Dr. Goutman. “These help to better define the genetic, environmental, and metabolic factors that increase and predict ALS risk,” he said.
But more work is needed, said Dr. Goutman. He noted that in the study, only 192 participants were diagnosed with ALS more than 5 years after enrollment. “This means additional large cohort studies are needed, especially those that reflect the diversity of the population, for us to solve the mystery of ALS and to prevent it,” he said.
Dr. Thompson and Dr. Goutman have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, new research shows.
The study also linked a higher ratio of total cholesterol to HDL with an increased risk for ALS. These findings, investigators noted, point to potential future biomarkers in screening for ALS and perhaps an approach to reduce risk or delay onset of ALS in the longer term.
“They may help build a biochemical picture of what’s going on and who might be at risk of developing ALS in the near future, particularly in people with a genetic predisposition to ALS,” study investigator Alexander G. Thompson, DPhil, Medical Research Council clinician scientist, Nuffield Department of Clinical Neurosciences, University of Oxford, United Kingdom, said in an interview.
He emphasized that although the current observational study cannot show cause and effect, such a relationship may exist.
The study was published online September 13 in the Journal of Neurology, Neurosurgery and Psychiatry.
Registry data
ALS is a disorder of progressive degeneration of upper and lower motor neurons. Genetic variants account for fewer than 15% of cases. The factors that are associated with the greatest risk are unclear.
To investigate, the researchers used data from the UK Biobank, a prospective cohort study of persons aged 39-72 years. Participants underwent an initial assessment between March 2006 and October 2010 and were followed for a median of 11.9 years.
In addition to providing demographic and health information, participants provided blood samples for biochemical analysis. This included measurements of total cholesterol, HDL, low-density lipoprotein (LDL) cholesterol, triglycerides, apoA1, apolipoprotein B (apoB), A1c, and creatinine.
Researchers used diagnostic codes in inpatient health records and death certificate information to verify ALS diagnoses.
The analysis included data from 502,409 participants. The mean age of the participants was 58 years, and 54.4% were women. During follow-up, 343 participants were diagnosed with ALS, yielding a crude incidence of 5.85 per 100,000 per year (95% confidence interval, 5.25-6.51).
After controlling for sex and age, results showed that higher HDL (hazard ratio, 0.84; 95% CI, 0.73-0.96; P = .010) and higher apoA1 (HR, 0.83; 95% CI, 0.72-0.94, P = .005) were associated with a reduced risk for subsequent ALS.
A higher ratio of total cholesterol to HDL was associated with increased ALS risk.
A rise in neurofilaments and other markers of neuronal loss typically occur within about a year of ALS symptom onset. To ensure that they were capturing participants whose blood samples were taken before the onset of neurodegeneration, the researchers performed a secondary analysis that excluded ALS diagnoses within 5 years of the baseline study visit.
Results of the analysis were largely consistent with models incorporating all participants with regard to magnitude and direction of associations. In addition, the findings persisted in models that controlled for statin use, smoking, and vascular disease.
Mechanism unclear
To more closely examine lipid status prior to ALS diagnosis, the researchers performed a nested case-control analysis that involved matching each participant who developed ALS with 20 participants of similar age, sex, and time of enrollment who did not develop the disease.
Linear models showed that levels of LDL and apoB, which are closely correlated, decrease over time in those who developed ALS. This was not the case for HDL and apoA1. “This suggests LDL levels are going down, and we think it’s happening quite some time before symptoms start, even before neurodegeneration starts,” said Dr. Thompson.
How blood lipid levels correlate with ALS risk is unclear. Dr. Thompson noted that LDL is an oxidative stressor and can provoke inflammation, whereas HDL is an antioxidant that is involved in healing. However, given that LDL and HDL don’t cross into the brain in great amounts, “the lipid changes may be a reflection of something else going on that contributes to the risk of ALS,” he said.
More evidence of a causal relationship is needed before any clinical implications can be drawn, including the potential manipulation of lipid levels to prevent ALS, said Dr. Thompson. In addition, even were such a relationship to be established, altering lipid levels in a healthy individual who has no family history of ALS would be unlikely to alter risk.
Dr. Thompson added that among those with a genetic predisposition, lipid changes “may be a marker or clue that something’s going wrong in the nervous system and that ALS might be about to start. That would be the ideal time to treat people at risk of ALS with gene therapy.”
Metabolism gone awry
Commenting on the findings, Stephen Goutman, MD, director, Pranger ALS Clinic, associate professor of neurology, Neuromuscular Program, University of Michigan, Ann Arbor, called the study “very interesting.” Of particular note was a trend of decreasing LDL and apoB levels prior to an ALS diagnosis, said Dr. Goutman.
The results are in agreement with several studies that show an alteration in metabolism in individuals with ALS, he said. “These altered metabolic pathways may provide some signal that something has gone awry,” he commented.
He agreed that an “ultimate goal” is to identify factors or biomarkers that can be used to predict whether individuals will develop ALS and to enable intervention to decrease the risk.
This new research highlights the value of population-based registries and large prospective cohorts, said Dr. Goutman. “These help to better define the genetic, environmental, and metabolic factors that increase and predict ALS risk,” he said.
But more work is needed, said Dr. Goutman. He noted that in the study, only 192 participants were diagnosed with ALS more than 5 years after enrollment. “This means additional large cohort studies are needed, especially those that reflect the diversity of the population, for us to solve the mystery of ALS and to prevent it,” he said.
Dr. Thompson and Dr. Goutman have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, new research shows.
The study also linked a higher ratio of total cholesterol to HDL with an increased risk for ALS. These findings, investigators noted, point to potential future biomarkers in screening for ALS and perhaps an approach to reduce risk or delay onset of ALS in the longer term.
“They may help build a biochemical picture of what’s going on and who might be at risk of developing ALS in the near future, particularly in people with a genetic predisposition to ALS,” study investigator Alexander G. Thompson, DPhil, Medical Research Council clinician scientist, Nuffield Department of Clinical Neurosciences, University of Oxford, United Kingdom, said in an interview.
He emphasized that although the current observational study cannot show cause and effect, such a relationship may exist.
The study was published online September 13 in the Journal of Neurology, Neurosurgery and Psychiatry.
Registry data
ALS is a disorder of progressive degeneration of upper and lower motor neurons. Genetic variants account for fewer than 15% of cases. The factors that are associated with the greatest risk are unclear.
To investigate, the researchers used data from the UK Biobank, a prospective cohort study of persons aged 39-72 years. Participants underwent an initial assessment between March 2006 and October 2010 and were followed for a median of 11.9 years.
In addition to providing demographic and health information, participants provided blood samples for biochemical analysis. This included measurements of total cholesterol, HDL, low-density lipoprotein (LDL) cholesterol, triglycerides, apoA1, apolipoprotein B (apoB), A1c, and creatinine.
Researchers used diagnostic codes in inpatient health records and death certificate information to verify ALS diagnoses.
The analysis included data from 502,409 participants. The mean age of the participants was 58 years, and 54.4% were women. During follow-up, 343 participants were diagnosed with ALS, yielding a crude incidence of 5.85 per 100,000 per year (95% confidence interval, 5.25-6.51).
After controlling for sex and age, results showed that higher HDL (hazard ratio, 0.84; 95% CI, 0.73-0.96; P = .010) and higher apoA1 (HR, 0.83; 95% CI, 0.72-0.94, P = .005) were associated with a reduced risk for subsequent ALS.
A higher ratio of total cholesterol to HDL was associated with increased ALS risk.
A rise in neurofilaments and other markers of neuronal loss typically occur within about a year of ALS symptom onset. To ensure that they were capturing participants whose blood samples were taken before the onset of neurodegeneration, the researchers performed a secondary analysis that excluded ALS diagnoses within 5 years of the baseline study visit.
Results of the analysis were largely consistent with models incorporating all participants with regard to magnitude and direction of associations. In addition, the findings persisted in models that controlled for statin use, smoking, and vascular disease.
Mechanism unclear
To more closely examine lipid status prior to ALS diagnosis, the researchers performed a nested case-control analysis that involved matching each participant who developed ALS with 20 participants of similar age, sex, and time of enrollment who did not develop the disease.
Linear models showed that levels of LDL and apoB, which are closely correlated, decrease over time in those who developed ALS. This was not the case for HDL and apoA1. “This suggests LDL levels are going down, and we think it’s happening quite some time before symptoms start, even before neurodegeneration starts,” said Dr. Thompson.
How blood lipid levels correlate with ALS risk is unclear. Dr. Thompson noted that LDL is an oxidative stressor and can provoke inflammation, whereas HDL is an antioxidant that is involved in healing. However, given that LDL and HDL don’t cross into the brain in great amounts, “the lipid changes may be a reflection of something else going on that contributes to the risk of ALS,” he said.
More evidence of a causal relationship is needed before any clinical implications can be drawn, including the potential manipulation of lipid levels to prevent ALS, said Dr. Thompson. In addition, even were such a relationship to be established, altering lipid levels in a healthy individual who has no family history of ALS would be unlikely to alter risk.
Dr. Thompson added that among those with a genetic predisposition, lipid changes “may be a marker or clue that something’s going wrong in the nervous system and that ALS might be about to start. That would be the ideal time to treat people at risk of ALS with gene therapy.”
Metabolism gone awry
Commenting on the findings, Stephen Goutman, MD, director, Pranger ALS Clinic, associate professor of neurology, Neuromuscular Program, University of Michigan, Ann Arbor, called the study “very interesting.” Of particular note was a trend of decreasing LDL and apoB levels prior to an ALS diagnosis, said Dr. Goutman.
The results are in agreement with several studies that show an alteration in metabolism in individuals with ALS, he said. “These altered metabolic pathways may provide some signal that something has gone awry,” he commented.
He agreed that an “ultimate goal” is to identify factors or biomarkers that can be used to predict whether individuals will develop ALS and to enable intervention to decrease the risk.
This new research highlights the value of population-based registries and large prospective cohorts, said Dr. Goutman. “These help to better define the genetic, environmental, and metabolic factors that increase and predict ALS risk,” he said.
But more work is needed, said Dr. Goutman. He noted that in the study, only 192 participants were diagnosed with ALS more than 5 years after enrollment. “This means additional large cohort studies are needed, especially those that reflect the diversity of the population, for us to solve the mystery of ALS and to prevent it,” he said.
Dr. Thompson and Dr. Goutman have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
From Journal of Neurology, Neurosurgery, and Psychiatry