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Large genetic study links 72 genes to autism spectrum disorders
according to a study published in Nature Genetics. The findings, based on analysis of more than 150,000 people’s genetics, arose from a collaboration of five research groups whose work included comparisons of ASD cohorts with separate cohorts of individuals with developmental delay or schizophrenia.
“We know that many genes, when mutated, contribute to autism,” and this study brought together “multiple types of mutations in a wide array of samples to get a much richer sense of the genes and genetic architecture involved in autism and other neurodevelopmental conditions,” co–senior author Joseph D. Buxbaum, PhD, director of the Seaver Autism Center for Research and Treatment at Mount Sinai and a professor at the Icahn School of Medicine at Mount Sinai, both in New York, said in a prepared statement. “This is significant in that we now have more insights as to the biology of the brain changes that underlie autism and more potential targets for treatment.”
Glen Elliott, PhD, MD, a clinical professor of psychiatry at Stanford (Calif.) University who was not involved in the study, said the paper is important paper for informing clinicians of where the basic research is headed. “We’re still in for a long road” before it bears fruit in terms of therapeutics. The value of studies like these, that investigate which genes are most associated with ASD, is that they may lead toward understanding the pathways in the brain that give rise to certain symptoms of ASD, which can then become therapeutic targets, Dr. Elliott said.
Investigating large cohorts
The researchers analyzed genetic exome sequencing data from 33 ASD cohorts with a total of 63,237 people and then compared these data with another cohort of people with developmental delay and a cohort of people with schizophrenia. The combined ASD cohorts included 15,036 individuals with ASD, 28,522 parents, and 5,492 unaffected siblings. The remaining participants were 5,591 people with ASD and 8,597 matched controls from case control studies.
In the ASD cohorts, the researchers identified 72 genes that were associated with ASD. De novo variants were eight times more likely in cases (4%) than in controls (0.5%). Ten genes occurred at least twice in ASD cases but never occurred in unaffected siblings.
Then the researchers integrated these ASD genetic data with a cohort of 91,605 people that included 31,058 people with developmental delay and their parents. Substantial overlap with gene mutations existed between these two cohorts: 70.1% of the genes related to developmental delay appeared linked to risk for ASD, and 86.6% of genes associated with ASD risk also had associations with developmental delay. Overall, the researchers identified 373 genes strongly associated with ASD and/or developmental delay and 664 genes with a likely association.
“Isolating genes that exert a greater effect on ASD than they do on other developmental delays has remained challenging due to the frequent comorbidity of these phenotypes,” wrote lead author Jack M. Fu, of Massachusetts General Hospital and Harvard Medical School, both in Boston, and colleagues. “Still, an estimated 13.4% of the transmission and de novo association–ASD genes show little evidence for association in the developmental delay cohort.”
ASD, developmental delay, and schizophrenia
When the researchers compared the cells where the genetic mutations occurred in fetal brains, they found that genes associated with developmental delay more often occurred in less differentiated cell types – less mature cells in the developmental process. Gene mutations associated with ASD, on the other hand, occurred in more mature cell types, particularly in maturing excitatory neurons and related cells.
”Our results are consistent with developmental delay-predominant genes being expressed earlier in development and in less differentiated cells than ASD-predominant genes,” they wrote.
The researchers also compared the specific gene mutations found in these two cohorts with a previously published set of 244 genes associated with schizophrenia. Of these, 234 genes are among those with a transmission and de novo association to ASD and/or developmental delay. Of the 72 genes linked to ASD, eight appear in the set of genes linked to schizophrenia, and 61 were associated with developmental delay, though these two subsets do not overlap each other much.
“The ASD-schizophrenia overlap was significantly enriched, while the developmental delay-schizophrenia overlap was not,” they reported. ”Together, these data suggest that one subset of ASD risk genes may overlap developmental delay while a different subset overlaps schizophrenia.”
Chasing therapy targets by backtracking through genes
The findings are a substantial step forward in understanding the potential genetic contribution to ASD, but they also highlight the challenges of eventually trying to use this information in a clinically meaningful way.
“Given the substantial overlap between the genes implicated in neurodevelopmental disorders writ large and those implicated directly in ASD, disentangling the relative impact of individual genes on neurodevelopment and phenotypic spectra is a daunting yet important challenge,” the researchers wrote. “To identify the key neurobiological features of ASD will likely require convergence of evidence from many ASD genes and studies.”
Dr. Elliott said the biggest takeaway from this study is a better understanding of how the paradigm has shifted away from finding “one gene” for autism or a cure based on genetics and more toward understanding the pathophysiology of symptoms that can point to therapies for better management of the condition.
“Basic researchers have completely changed the strategy for trying to understand the biology of major disorders,” including, in this case, autism, Dr. Elliott said. “The intent is to try to find the underlying systems [in the brain] by backtracking through genes. Meanwhile, given that scientists have made substantial progress in identifying genes that have specific effects on brain development, “the hope is that will mesh with this kind of research, to begin to identify systems that might ultimately be targets for treating.”
The end goal is to be able to offer targeted approaches, based on the pathways causing a symptom, which can be linked backward to a gene.
”So this is not going to offer an immediate cure – it’s probably not going to offer a cure at all – but it may actually lead to much more targeted medications than we currently have for specific types of symptoms within the autism spectrum,” Dr. Elliott said. “What they’re trying to do, ultimately, is to say, when this system is really badly affected because of a genetic abnormality, even though that genetic abnormality is very rare, it leads to these specific kinds of symptoms. If we can find out the neuroregulators underlying that change, then that would be the target, even if that gene were not present.”
The research was funded by the Simons Foundation for Autism Research Initiative, the SPARK project, the National Human Genome Research Institute Home, the National Institute of Mental Health, the National Institute of Child Health and Development, AMED, and the Beatrice and Samuel Seaver Foundation. Five authors reported financial disclosures linked to Desitin, Roche, BioMarin, BrigeBio Pharma, Illumina, Levo Therapeutics, and Microsoft.
according to a study published in Nature Genetics. The findings, based on analysis of more than 150,000 people’s genetics, arose from a collaboration of five research groups whose work included comparisons of ASD cohorts with separate cohorts of individuals with developmental delay or schizophrenia.
“We know that many genes, when mutated, contribute to autism,” and this study brought together “multiple types of mutations in a wide array of samples to get a much richer sense of the genes and genetic architecture involved in autism and other neurodevelopmental conditions,” co–senior author Joseph D. Buxbaum, PhD, director of the Seaver Autism Center for Research and Treatment at Mount Sinai and a professor at the Icahn School of Medicine at Mount Sinai, both in New York, said in a prepared statement. “This is significant in that we now have more insights as to the biology of the brain changes that underlie autism and more potential targets for treatment.”
Glen Elliott, PhD, MD, a clinical professor of psychiatry at Stanford (Calif.) University who was not involved in the study, said the paper is important paper for informing clinicians of where the basic research is headed. “We’re still in for a long road” before it bears fruit in terms of therapeutics. The value of studies like these, that investigate which genes are most associated with ASD, is that they may lead toward understanding the pathways in the brain that give rise to certain symptoms of ASD, which can then become therapeutic targets, Dr. Elliott said.
Investigating large cohorts
The researchers analyzed genetic exome sequencing data from 33 ASD cohorts with a total of 63,237 people and then compared these data with another cohort of people with developmental delay and a cohort of people with schizophrenia. The combined ASD cohorts included 15,036 individuals with ASD, 28,522 parents, and 5,492 unaffected siblings. The remaining participants were 5,591 people with ASD and 8,597 matched controls from case control studies.
In the ASD cohorts, the researchers identified 72 genes that were associated with ASD. De novo variants were eight times more likely in cases (4%) than in controls (0.5%). Ten genes occurred at least twice in ASD cases but never occurred in unaffected siblings.
Then the researchers integrated these ASD genetic data with a cohort of 91,605 people that included 31,058 people with developmental delay and their parents. Substantial overlap with gene mutations existed between these two cohorts: 70.1% of the genes related to developmental delay appeared linked to risk for ASD, and 86.6% of genes associated with ASD risk also had associations with developmental delay. Overall, the researchers identified 373 genes strongly associated with ASD and/or developmental delay and 664 genes with a likely association.
“Isolating genes that exert a greater effect on ASD than they do on other developmental delays has remained challenging due to the frequent comorbidity of these phenotypes,” wrote lead author Jack M. Fu, of Massachusetts General Hospital and Harvard Medical School, both in Boston, and colleagues. “Still, an estimated 13.4% of the transmission and de novo association–ASD genes show little evidence for association in the developmental delay cohort.”
ASD, developmental delay, and schizophrenia
When the researchers compared the cells where the genetic mutations occurred in fetal brains, they found that genes associated with developmental delay more often occurred in less differentiated cell types – less mature cells in the developmental process. Gene mutations associated with ASD, on the other hand, occurred in more mature cell types, particularly in maturing excitatory neurons and related cells.
”Our results are consistent with developmental delay-predominant genes being expressed earlier in development and in less differentiated cells than ASD-predominant genes,” they wrote.
The researchers also compared the specific gene mutations found in these two cohorts with a previously published set of 244 genes associated with schizophrenia. Of these, 234 genes are among those with a transmission and de novo association to ASD and/or developmental delay. Of the 72 genes linked to ASD, eight appear in the set of genes linked to schizophrenia, and 61 were associated with developmental delay, though these two subsets do not overlap each other much.
“The ASD-schizophrenia overlap was significantly enriched, while the developmental delay-schizophrenia overlap was not,” they reported. ”Together, these data suggest that one subset of ASD risk genes may overlap developmental delay while a different subset overlaps schizophrenia.”
Chasing therapy targets by backtracking through genes
The findings are a substantial step forward in understanding the potential genetic contribution to ASD, but they also highlight the challenges of eventually trying to use this information in a clinically meaningful way.
“Given the substantial overlap between the genes implicated in neurodevelopmental disorders writ large and those implicated directly in ASD, disentangling the relative impact of individual genes on neurodevelopment and phenotypic spectra is a daunting yet important challenge,” the researchers wrote. “To identify the key neurobiological features of ASD will likely require convergence of evidence from many ASD genes and studies.”
Dr. Elliott said the biggest takeaway from this study is a better understanding of how the paradigm has shifted away from finding “one gene” for autism or a cure based on genetics and more toward understanding the pathophysiology of symptoms that can point to therapies for better management of the condition.
“Basic researchers have completely changed the strategy for trying to understand the biology of major disorders,” including, in this case, autism, Dr. Elliott said. “The intent is to try to find the underlying systems [in the brain] by backtracking through genes. Meanwhile, given that scientists have made substantial progress in identifying genes that have specific effects on brain development, “the hope is that will mesh with this kind of research, to begin to identify systems that might ultimately be targets for treating.”
The end goal is to be able to offer targeted approaches, based on the pathways causing a symptom, which can be linked backward to a gene.
”So this is not going to offer an immediate cure – it’s probably not going to offer a cure at all – but it may actually lead to much more targeted medications than we currently have for specific types of symptoms within the autism spectrum,” Dr. Elliott said. “What they’re trying to do, ultimately, is to say, when this system is really badly affected because of a genetic abnormality, even though that genetic abnormality is very rare, it leads to these specific kinds of symptoms. If we can find out the neuroregulators underlying that change, then that would be the target, even if that gene were not present.”
The research was funded by the Simons Foundation for Autism Research Initiative, the SPARK project, the National Human Genome Research Institute Home, the National Institute of Mental Health, the National Institute of Child Health and Development, AMED, and the Beatrice and Samuel Seaver Foundation. Five authors reported financial disclosures linked to Desitin, Roche, BioMarin, BrigeBio Pharma, Illumina, Levo Therapeutics, and Microsoft.
according to a study published in Nature Genetics. The findings, based on analysis of more than 150,000 people’s genetics, arose from a collaboration of five research groups whose work included comparisons of ASD cohorts with separate cohorts of individuals with developmental delay or schizophrenia.
“We know that many genes, when mutated, contribute to autism,” and this study brought together “multiple types of mutations in a wide array of samples to get a much richer sense of the genes and genetic architecture involved in autism and other neurodevelopmental conditions,” co–senior author Joseph D. Buxbaum, PhD, director of the Seaver Autism Center for Research and Treatment at Mount Sinai and a professor at the Icahn School of Medicine at Mount Sinai, both in New York, said in a prepared statement. “This is significant in that we now have more insights as to the biology of the brain changes that underlie autism and more potential targets for treatment.”
Glen Elliott, PhD, MD, a clinical professor of psychiatry at Stanford (Calif.) University who was not involved in the study, said the paper is important paper for informing clinicians of where the basic research is headed. “We’re still in for a long road” before it bears fruit in terms of therapeutics. The value of studies like these, that investigate which genes are most associated with ASD, is that they may lead toward understanding the pathways in the brain that give rise to certain symptoms of ASD, which can then become therapeutic targets, Dr. Elliott said.
Investigating large cohorts
The researchers analyzed genetic exome sequencing data from 33 ASD cohorts with a total of 63,237 people and then compared these data with another cohort of people with developmental delay and a cohort of people with schizophrenia. The combined ASD cohorts included 15,036 individuals with ASD, 28,522 parents, and 5,492 unaffected siblings. The remaining participants were 5,591 people with ASD and 8,597 matched controls from case control studies.
In the ASD cohorts, the researchers identified 72 genes that were associated with ASD. De novo variants were eight times more likely in cases (4%) than in controls (0.5%). Ten genes occurred at least twice in ASD cases but never occurred in unaffected siblings.
Then the researchers integrated these ASD genetic data with a cohort of 91,605 people that included 31,058 people with developmental delay and their parents. Substantial overlap with gene mutations existed between these two cohorts: 70.1% of the genes related to developmental delay appeared linked to risk for ASD, and 86.6% of genes associated with ASD risk also had associations with developmental delay. Overall, the researchers identified 373 genes strongly associated with ASD and/or developmental delay and 664 genes with a likely association.
“Isolating genes that exert a greater effect on ASD than they do on other developmental delays has remained challenging due to the frequent comorbidity of these phenotypes,” wrote lead author Jack M. Fu, of Massachusetts General Hospital and Harvard Medical School, both in Boston, and colleagues. “Still, an estimated 13.4% of the transmission and de novo association–ASD genes show little evidence for association in the developmental delay cohort.”
ASD, developmental delay, and schizophrenia
When the researchers compared the cells where the genetic mutations occurred in fetal brains, they found that genes associated with developmental delay more often occurred in less differentiated cell types – less mature cells in the developmental process. Gene mutations associated with ASD, on the other hand, occurred in more mature cell types, particularly in maturing excitatory neurons and related cells.
”Our results are consistent with developmental delay-predominant genes being expressed earlier in development and in less differentiated cells than ASD-predominant genes,” they wrote.
The researchers also compared the specific gene mutations found in these two cohorts with a previously published set of 244 genes associated with schizophrenia. Of these, 234 genes are among those with a transmission and de novo association to ASD and/or developmental delay. Of the 72 genes linked to ASD, eight appear in the set of genes linked to schizophrenia, and 61 were associated with developmental delay, though these two subsets do not overlap each other much.
“The ASD-schizophrenia overlap was significantly enriched, while the developmental delay-schizophrenia overlap was not,” they reported. ”Together, these data suggest that one subset of ASD risk genes may overlap developmental delay while a different subset overlaps schizophrenia.”
Chasing therapy targets by backtracking through genes
The findings are a substantial step forward in understanding the potential genetic contribution to ASD, but they also highlight the challenges of eventually trying to use this information in a clinically meaningful way.
“Given the substantial overlap between the genes implicated in neurodevelopmental disorders writ large and those implicated directly in ASD, disentangling the relative impact of individual genes on neurodevelopment and phenotypic spectra is a daunting yet important challenge,” the researchers wrote. “To identify the key neurobiological features of ASD will likely require convergence of evidence from many ASD genes and studies.”
Dr. Elliott said the biggest takeaway from this study is a better understanding of how the paradigm has shifted away from finding “one gene” for autism or a cure based on genetics and more toward understanding the pathophysiology of symptoms that can point to therapies for better management of the condition.
“Basic researchers have completely changed the strategy for trying to understand the biology of major disorders,” including, in this case, autism, Dr. Elliott said. “The intent is to try to find the underlying systems [in the brain] by backtracking through genes. Meanwhile, given that scientists have made substantial progress in identifying genes that have specific effects on brain development, “the hope is that will mesh with this kind of research, to begin to identify systems that might ultimately be targets for treating.”
The end goal is to be able to offer targeted approaches, based on the pathways causing a symptom, which can be linked backward to a gene.
”So this is not going to offer an immediate cure – it’s probably not going to offer a cure at all – but it may actually lead to much more targeted medications than we currently have for specific types of symptoms within the autism spectrum,” Dr. Elliott said. “What they’re trying to do, ultimately, is to say, when this system is really badly affected because of a genetic abnormality, even though that genetic abnormality is very rare, it leads to these specific kinds of symptoms. If we can find out the neuroregulators underlying that change, then that would be the target, even if that gene were not present.”
The research was funded by the Simons Foundation for Autism Research Initiative, the SPARK project, the National Human Genome Research Institute Home, the National Institute of Mental Health, the National Institute of Child Health and Development, AMED, and the Beatrice and Samuel Seaver Foundation. Five authors reported financial disclosures linked to Desitin, Roche, BioMarin, BrigeBio Pharma, Illumina, Levo Therapeutics, and Microsoft.
FROM NATURE GENETICS
‘Conservative’ USPSTF primary prevention statin guidance finalized
Questions about how to prescribe statins for primary prevention abound more than 3 decades after the drugs swept into clinical practice to become a first-line medical approach to cutting cardiovascular (CV) risk. Statin usage recommendations from different bodies can vary in ways both limited and fundamental, spurring the kind of debate that accompanies such a document newly issued by the United States Preventive Services Task Force.
The document, little changed from the draft guidance released for public comment in February, was published online Aug. 23 in JAMA and the USPSTF website. It replaces a similar document issued by the task force in 2016.
The guidance has much in common with, but also sharp differences from, the influential 2018 guidelines on blood cholesterol management developed by the American College of Cardiology, American Heart Association, and 10 other medical societies.
And it is provocative enough to elicit at least four editorials issued the same day across the JAMA family of journals. They highlight key differences between the two documents, among them the USPSTF guidance’s consistent, narrow reliance on 7.5% and 10% cut points for 10-year risk levels as estimated from the ACC/AHA pooled cohort equations (PCE).
The guidance pairs the 10-year risk metric with at least one of only four prescribed CV risk factors to arrive at a limited choice of statin therapy recommendations. But its decision process isn’t bolstered by coronary artery calcium (CAC) scores or the prespecified “risk enhancers” that allowed the ACC/AHA-multisociety guidelines to be applied broadly and still be closely personalized. Those guidelines provide more PCE-based risk tiers for greater discrimination of risk and allow statins to be considered across a broader age group.
The USPSTF guidance’s evidence base consists of 23 clinical trials and three observational studies that directly compared a statin to either placebo or no statin, task force member John B. Wong, MD, Tufts University School of Medicine, Boston, told this news organization.
“In either kind of study, we found that the vast majority of patients had one or more of four risk factors – dyslipidemia, hypertension, diabetes, or smoking. So, when we categorized high risk or increased risk, we included the presence of one or more of those risk factors,” said Dr. Wong, who is director of comparative effectiveness research at Tufts Clinical Translational Science Institute.
‘Sensible and practical’
The USPSTF guidance applies only to adults aged 40-75 without CV signs or symptoms and recommends a statin prescription for persons at “high risk,” that is with an estimated 10-year PCE-based risk for death or CV events of 10% or higher plus at least one of the four risk factors, a level B recommendation.
It recommends that “clinicians selectively offer a statin” to such persons at “increased risk,” who have at least one of the risk factors and an estimated 10-year risk for death or CV events of 7.5% to less than 10%, a level C recommendation. “The likelihood of benefit is smaller in this group” than in persons at high risk, the document states.
“These recommendations from the USPSTF are sensible and practical,” states Salim S. Virani, MD, PhD, DeBakey Veterans Affairs Medical Center, Houston, in a related editorial published the same day in JAMA Network Open. He calls the former B-level recommendation “a conservative approach” and the latter C-level recommendation a “nuanced approach.”
Both are “understandable” given that some studies suggest that the PCE may overestimate the CV risk, Dr. Virani observes. “On the other hand, statin therapy has been shown to be efficacious” at 10-year CV-risk levels down to about 5%.
The USPSTF document “I think is going to perpetuate a problem that we have in this country, which is vast undertreatment of lipids,” Eric D. Peterson, MD, MPH, University of Texas Southwestern Medical Center, Dallas, said in an interview.
“We have a ton of good drugs that can lower cholesterol like crazy. If you lower cholesterol a lot, you improve outcomes,” he said. Dyslipidemia needs to be more widely and consistently treated, but “right now we have a pool of people in primary prevention who undertreat lipids and wait until disease happens – and then cardiologists get engaged. That’s an avoidable miss,” Dr. Peterson adds. He and JAMA Cardiology associate editor Ann Marie Navar, MD, PhD, provided JAMA with an editorial that accompanies the USPSTF guidance.
“My own personal bias would be that the [ACC/AHA-multisociety guidelines] are closer to being right,” Dr. Peterson said. They – unlike the USPSTF guidance – cover people with risk levels below 7.5%, down to at least 5%. They allow risk enhancers like metabolic syndrome, inflammatory diseases, or family history into the decision process. “And they’re more aggressive in diabetes and more aggressive in older people,” he said.
Higher threshold for therapy
The USPSTF guidance also explicitly omits some high-risk groups and makes little accommodation for others who might especially benefit from statins, several of the editorials contend. For example, states a related JAMA Cardiology editorial published the same day, “The USPSTF does not comment on familial hypercholesterolemia or an LDL-C level of 190 mg/dL or higher,” yet they are covered by the ACC/AHA-multispecialty guidelines.
In addition, write the editorialists, led by Neil J. Stone, MD, Northwestern University, Chicago, “the USPSTF uses a slightly higher threshold for initiation of statin therapy” than was used in the ACC/AHA-multisociety guidelines. USPSTF, for example, calls for 10-year risk to reach 10% before recommending a statin prescription.
“One concern about the USPSTF setting the bar higher for statin initiation is that it reduces the number of young patients (age 40-50 years) at risk for premature myocardial infarction considered for treatment,” write Dr. Stone and colleagues.
That may be related to a weakness of the PCE-based decision process. “Because the PCE estimates of 10-year CV disease risk rely so heavily on age, sex, and race, use of these estimates to identify candidates for statins results in significant skewing of the population recommended for statins,” write Dr. Navar and Dr. Peterson in their JAMA editorial.
The risk enhancers in the ACC/AHA-multispecialty guidelines, about a dozen of them, compensate for that limitation to some extent. But the PCE-dominated USPSTF risk estimates will likely miss some groups that could potentially benefit from statin therapy, Dr. Peterson agreed in an interview.
For example, younger adults facing years of high LDL-cholesterol levels could easily have PCE-based 10-year risk below 10%. “Having a high LDL over a lifetime puts you at really high risk,” he said. “Young people are missed even though their longitudinal risk is high.” So, by waiting for the lofty 10% level of risk over 10 years, “we limit the use of medicine that’s pretty cheap and highly effective.”
Dose intensity, adverse events
Also at variance from the ACC/AHA-multispecialty guidelines, the USPSTF states that, “Based on available evidence, use of moderate-intensity statin therapy seems reasonable for the primary prevention of CV disease in most persons.”
The task force specifically explored whether evidence supports some use of high-intensity vs. moderate-intensity statins, Tufts University’s Dr. Wong said. “We found only one study that looked at that particular question, and it didn’t give us a strong answer.” An elevated rosuvastatin-related diabetes risk was apparent in the JUPITER trial, “but for the other studies, we did not find that association.”
Most of the studies that explored statins for reducing risk for a first stroke or myocardial infarction used a moderate-dose statin, Dr. Wong said. “So that’s what we would usually recommend.”
But, Dr. Virani writes, consistent with the ACC/AHA-multispecialty guidelines, “clinicians should consider titrating the intensity of therapy to the risk of the individual.” Persons in certain high-risk primary prevention groups, such as those with end-organ injury from diabetes or LDL cholesterol at least 190 mg/dL, “may derive further benefit from the use of high-intensity statin therapy.”
Low-intensity statins are another potential option, but “in contrast with its 2016 recommendations, the USPSTF no longer recommends use of low-intensity statins in certain situations,” observes a fourth editorial published the same day in JAMA Internal Medicine, with lead author Anand R. Habib, MD, MPhil, and senior author Rita F. Redberg, MD, MSc, both of the University of California, San Francisco. Dr. Redberg is the journal’s editor and has long expressed cautions about statin safety.
“While it is understandable that the Task Force was limited by lack of data on dosing, this change is unfortunate for patients because the frequency of adverse effects increases as the statin dose increases,” the editorial states. Although USPSTF did not find statistically significant harm from the drugs, “in clinical practice, adverse events are commonly reported with use of statins.”
It continues: “At present, there are further reasons to curb our enthusiasm about the use of statins for primary prevention of CV disease.” To illustrate, the editorial questioned primary-prevention statins’ balance of risk vs. clinically meaningful benefit, not benefit that is merely statistically significant.
“The purported benefits of statins in terms of relative risk reduction are fairly constant across baseline lipid levels and cardiovascular risk score categories for primary prevention,” the editorial states.
“Therefore, the absolute benefit for those in lower-risk categories is likely small given that their baseline absolute risk is low, while the chance of adverse effects is constant across risk categories.”
However, USPSTF states, “In pooled analyses of trial data, statin therapy was not associated with increased risk of study withdrawal due to adverse events or serious adverse events.” Nor did it find significant associations with cancers, liver enzyme abnormalities, or diabetes, including new-onset diabetes.
And, the USPSTF adds, “Evidence on the association between statins and renal or cognitive harms is very limited but does not indicate increased risk.”
USPSTF is supported by the U.S. Agency for Healthcare Research and Quality. Dr. Virani discloses receiving grants from the Department of Veterans Affairs, National Institutes of Health, and the World Heart Federation; and personal fees from the American College of Cardiology. Dr. Peterson discloses serving on the JAMA editorial board and receiving research support to his institution from Amgen, Bristol-Myers Squibb, Esperion, and Janssen; and consulting fees from Novo Nordisk, Bayer, and Novartis. Dr. Navar discloses receiving research support to her institution from Amgen, Bristol-Myers Squibb, Esperion, and Janssen; and receiving honoraria and consulting fees from AstraZeneca, Boehringer Ingelheim, Bayer, Janssen, Lilly, Novo Nordisk, Novartis, New Amsterdam, and Pfizer. Dr. Stone discloses receiving an honorarium from Knowledge to Practice, an educational company not associated with the pharmaceutical industry; disclosures for the other authors are in the report. Dr. Redberg discloses receiving research funding from the Arnold Ventures Foundation and the Greenwall Foundation.
A version of this article first appeared on Medscape.com.
Questions about how to prescribe statins for primary prevention abound more than 3 decades after the drugs swept into clinical practice to become a first-line medical approach to cutting cardiovascular (CV) risk. Statin usage recommendations from different bodies can vary in ways both limited and fundamental, spurring the kind of debate that accompanies such a document newly issued by the United States Preventive Services Task Force.
The document, little changed from the draft guidance released for public comment in February, was published online Aug. 23 in JAMA and the USPSTF website. It replaces a similar document issued by the task force in 2016.
The guidance has much in common with, but also sharp differences from, the influential 2018 guidelines on blood cholesterol management developed by the American College of Cardiology, American Heart Association, and 10 other medical societies.
And it is provocative enough to elicit at least four editorials issued the same day across the JAMA family of journals. They highlight key differences between the two documents, among them the USPSTF guidance’s consistent, narrow reliance on 7.5% and 10% cut points for 10-year risk levels as estimated from the ACC/AHA pooled cohort equations (PCE).
The guidance pairs the 10-year risk metric with at least one of only four prescribed CV risk factors to arrive at a limited choice of statin therapy recommendations. But its decision process isn’t bolstered by coronary artery calcium (CAC) scores or the prespecified “risk enhancers” that allowed the ACC/AHA-multisociety guidelines to be applied broadly and still be closely personalized. Those guidelines provide more PCE-based risk tiers for greater discrimination of risk and allow statins to be considered across a broader age group.
The USPSTF guidance’s evidence base consists of 23 clinical trials and three observational studies that directly compared a statin to either placebo or no statin, task force member John B. Wong, MD, Tufts University School of Medicine, Boston, told this news organization.
“In either kind of study, we found that the vast majority of patients had one or more of four risk factors – dyslipidemia, hypertension, diabetes, or smoking. So, when we categorized high risk or increased risk, we included the presence of one or more of those risk factors,” said Dr. Wong, who is director of comparative effectiveness research at Tufts Clinical Translational Science Institute.
‘Sensible and practical’
The USPSTF guidance applies only to adults aged 40-75 without CV signs or symptoms and recommends a statin prescription for persons at “high risk,” that is with an estimated 10-year PCE-based risk for death or CV events of 10% or higher plus at least one of the four risk factors, a level B recommendation.
It recommends that “clinicians selectively offer a statin” to such persons at “increased risk,” who have at least one of the risk factors and an estimated 10-year risk for death or CV events of 7.5% to less than 10%, a level C recommendation. “The likelihood of benefit is smaller in this group” than in persons at high risk, the document states.
“These recommendations from the USPSTF are sensible and practical,” states Salim S. Virani, MD, PhD, DeBakey Veterans Affairs Medical Center, Houston, in a related editorial published the same day in JAMA Network Open. He calls the former B-level recommendation “a conservative approach” and the latter C-level recommendation a “nuanced approach.”
Both are “understandable” given that some studies suggest that the PCE may overestimate the CV risk, Dr. Virani observes. “On the other hand, statin therapy has been shown to be efficacious” at 10-year CV-risk levels down to about 5%.
The USPSTF document “I think is going to perpetuate a problem that we have in this country, which is vast undertreatment of lipids,” Eric D. Peterson, MD, MPH, University of Texas Southwestern Medical Center, Dallas, said in an interview.
“We have a ton of good drugs that can lower cholesterol like crazy. If you lower cholesterol a lot, you improve outcomes,” he said. Dyslipidemia needs to be more widely and consistently treated, but “right now we have a pool of people in primary prevention who undertreat lipids and wait until disease happens – and then cardiologists get engaged. That’s an avoidable miss,” Dr. Peterson adds. He and JAMA Cardiology associate editor Ann Marie Navar, MD, PhD, provided JAMA with an editorial that accompanies the USPSTF guidance.
“My own personal bias would be that the [ACC/AHA-multisociety guidelines] are closer to being right,” Dr. Peterson said. They – unlike the USPSTF guidance – cover people with risk levels below 7.5%, down to at least 5%. They allow risk enhancers like metabolic syndrome, inflammatory diseases, or family history into the decision process. “And they’re more aggressive in diabetes and more aggressive in older people,” he said.
Higher threshold for therapy
The USPSTF guidance also explicitly omits some high-risk groups and makes little accommodation for others who might especially benefit from statins, several of the editorials contend. For example, states a related JAMA Cardiology editorial published the same day, “The USPSTF does not comment on familial hypercholesterolemia or an LDL-C level of 190 mg/dL or higher,” yet they are covered by the ACC/AHA-multispecialty guidelines.
In addition, write the editorialists, led by Neil J. Stone, MD, Northwestern University, Chicago, “the USPSTF uses a slightly higher threshold for initiation of statin therapy” than was used in the ACC/AHA-multisociety guidelines. USPSTF, for example, calls for 10-year risk to reach 10% before recommending a statin prescription.
“One concern about the USPSTF setting the bar higher for statin initiation is that it reduces the number of young patients (age 40-50 years) at risk for premature myocardial infarction considered for treatment,” write Dr. Stone and colleagues.
That may be related to a weakness of the PCE-based decision process. “Because the PCE estimates of 10-year CV disease risk rely so heavily on age, sex, and race, use of these estimates to identify candidates for statins results in significant skewing of the population recommended for statins,” write Dr. Navar and Dr. Peterson in their JAMA editorial.
The risk enhancers in the ACC/AHA-multispecialty guidelines, about a dozen of them, compensate for that limitation to some extent. But the PCE-dominated USPSTF risk estimates will likely miss some groups that could potentially benefit from statin therapy, Dr. Peterson agreed in an interview.
For example, younger adults facing years of high LDL-cholesterol levels could easily have PCE-based 10-year risk below 10%. “Having a high LDL over a lifetime puts you at really high risk,” he said. “Young people are missed even though their longitudinal risk is high.” So, by waiting for the lofty 10% level of risk over 10 years, “we limit the use of medicine that’s pretty cheap and highly effective.”
Dose intensity, adverse events
Also at variance from the ACC/AHA-multispecialty guidelines, the USPSTF states that, “Based on available evidence, use of moderate-intensity statin therapy seems reasonable for the primary prevention of CV disease in most persons.”
The task force specifically explored whether evidence supports some use of high-intensity vs. moderate-intensity statins, Tufts University’s Dr. Wong said. “We found only one study that looked at that particular question, and it didn’t give us a strong answer.” An elevated rosuvastatin-related diabetes risk was apparent in the JUPITER trial, “but for the other studies, we did not find that association.”
Most of the studies that explored statins for reducing risk for a first stroke or myocardial infarction used a moderate-dose statin, Dr. Wong said. “So that’s what we would usually recommend.”
But, Dr. Virani writes, consistent with the ACC/AHA-multispecialty guidelines, “clinicians should consider titrating the intensity of therapy to the risk of the individual.” Persons in certain high-risk primary prevention groups, such as those with end-organ injury from diabetes or LDL cholesterol at least 190 mg/dL, “may derive further benefit from the use of high-intensity statin therapy.”
Low-intensity statins are another potential option, but “in contrast with its 2016 recommendations, the USPSTF no longer recommends use of low-intensity statins in certain situations,” observes a fourth editorial published the same day in JAMA Internal Medicine, with lead author Anand R. Habib, MD, MPhil, and senior author Rita F. Redberg, MD, MSc, both of the University of California, San Francisco. Dr. Redberg is the journal’s editor and has long expressed cautions about statin safety.
“While it is understandable that the Task Force was limited by lack of data on dosing, this change is unfortunate for patients because the frequency of adverse effects increases as the statin dose increases,” the editorial states. Although USPSTF did not find statistically significant harm from the drugs, “in clinical practice, adverse events are commonly reported with use of statins.”
It continues: “At present, there are further reasons to curb our enthusiasm about the use of statins for primary prevention of CV disease.” To illustrate, the editorial questioned primary-prevention statins’ balance of risk vs. clinically meaningful benefit, not benefit that is merely statistically significant.
“The purported benefits of statins in terms of relative risk reduction are fairly constant across baseline lipid levels and cardiovascular risk score categories for primary prevention,” the editorial states.
“Therefore, the absolute benefit for those in lower-risk categories is likely small given that their baseline absolute risk is low, while the chance of adverse effects is constant across risk categories.”
However, USPSTF states, “In pooled analyses of trial data, statin therapy was not associated with increased risk of study withdrawal due to adverse events or serious adverse events.” Nor did it find significant associations with cancers, liver enzyme abnormalities, or diabetes, including new-onset diabetes.
And, the USPSTF adds, “Evidence on the association between statins and renal or cognitive harms is very limited but does not indicate increased risk.”
USPSTF is supported by the U.S. Agency for Healthcare Research and Quality. Dr. Virani discloses receiving grants from the Department of Veterans Affairs, National Institutes of Health, and the World Heart Federation; and personal fees from the American College of Cardiology. Dr. Peterson discloses serving on the JAMA editorial board and receiving research support to his institution from Amgen, Bristol-Myers Squibb, Esperion, and Janssen; and consulting fees from Novo Nordisk, Bayer, and Novartis. Dr. Navar discloses receiving research support to her institution from Amgen, Bristol-Myers Squibb, Esperion, and Janssen; and receiving honoraria and consulting fees from AstraZeneca, Boehringer Ingelheim, Bayer, Janssen, Lilly, Novo Nordisk, Novartis, New Amsterdam, and Pfizer. Dr. Stone discloses receiving an honorarium from Knowledge to Practice, an educational company not associated with the pharmaceutical industry; disclosures for the other authors are in the report. Dr. Redberg discloses receiving research funding from the Arnold Ventures Foundation and the Greenwall Foundation.
A version of this article first appeared on Medscape.com.
Questions about how to prescribe statins for primary prevention abound more than 3 decades after the drugs swept into clinical practice to become a first-line medical approach to cutting cardiovascular (CV) risk. Statin usage recommendations from different bodies can vary in ways both limited and fundamental, spurring the kind of debate that accompanies such a document newly issued by the United States Preventive Services Task Force.
The document, little changed from the draft guidance released for public comment in February, was published online Aug. 23 in JAMA and the USPSTF website. It replaces a similar document issued by the task force in 2016.
The guidance has much in common with, but also sharp differences from, the influential 2018 guidelines on blood cholesterol management developed by the American College of Cardiology, American Heart Association, and 10 other medical societies.
And it is provocative enough to elicit at least four editorials issued the same day across the JAMA family of journals. They highlight key differences between the two documents, among them the USPSTF guidance’s consistent, narrow reliance on 7.5% and 10% cut points for 10-year risk levels as estimated from the ACC/AHA pooled cohort equations (PCE).
The guidance pairs the 10-year risk metric with at least one of only four prescribed CV risk factors to arrive at a limited choice of statin therapy recommendations. But its decision process isn’t bolstered by coronary artery calcium (CAC) scores or the prespecified “risk enhancers” that allowed the ACC/AHA-multisociety guidelines to be applied broadly and still be closely personalized. Those guidelines provide more PCE-based risk tiers for greater discrimination of risk and allow statins to be considered across a broader age group.
The USPSTF guidance’s evidence base consists of 23 clinical trials and three observational studies that directly compared a statin to either placebo or no statin, task force member John B. Wong, MD, Tufts University School of Medicine, Boston, told this news organization.
“In either kind of study, we found that the vast majority of patients had one or more of four risk factors – dyslipidemia, hypertension, diabetes, or smoking. So, when we categorized high risk or increased risk, we included the presence of one or more of those risk factors,” said Dr. Wong, who is director of comparative effectiveness research at Tufts Clinical Translational Science Institute.
‘Sensible and practical’
The USPSTF guidance applies only to adults aged 40-75 without CV signs or symptoms and recommends a statin prescription for persons at “high risk,” that is with an estimated 10-year PCE-based risk for death or CV events of 10% or higher plus at least one of the four risk factors, a level B recommendation.
It recommends that “clinicians selectively offer a statin” to such persons at “increased risk,” who have at least one of the risk factors and an estimated 10-year risk for death or CV events of 7.5% to less than 10%, a level C recommendation. “The likelihood of benefit is smaller in this group” than in persons at high risk, the document states.
“These recommendations from the USPSTF are sensible and practical,” states Salim S. Virani, MD, PhD, DeBakey Veterans Affairs Medical Center, Houston, in a related editorial published the same day in JAMA Network Open. He calls the former B-level recommendation “a conservative approach” and the latter C-level recommendation a “nuanced approach.”
Both are “understandable” given that some studies suggest that the PCE may overestimate the CV risk, Dr. Virani observes. “On the other hand, statin therapy has been shown to be efficacious” at 10-year CV-risk levels down to about 5%.
The USPSTF document “I think is going to perpetuate a problem that we have in this country, which is vast undertreatment of lipids,” Eric D. Peterson, MD, MPH, University of Texas Southwestern Medical Center, Dallas, said in an interview.
“We have a ton of good drugs that can lower cholesterol like crazy. If you lower cholesterol a lot, you improve outcomes,” he said. Dyslipidemia needs to be more widely and consistently treated, but “right now we have a pool of people in primary prevention who undertreat lipids and wait until disease happens – and then cardiologists get engaged. That’s an avoidable miss,” Dr. Peterson adds. He and JAMA Cardiology associate editor Ann Marie Navar, MD, PhD, provided JAMA with an editorial that accompanies the USPSTF guidance.
“My own personal bias would be that the [ACC/AHA-multisociety guidelines] are closer to being right,” Dr. Peterson said. They – unlike the USPSTF guidance – cover people with risk levels below 7.5%, down to at least 5%. They allow risk enhancers like metabolic syndrome, inflammatory diseases, or family history into the decision process. “And they’re more aggressive in diabetes and more aggressive in older people,” he said.
Higher threshold for therapy
The USPSTF guidance also explicitly omits some high-risk groups and makes little accommodation for others who might especially benefit from statins, several of the editorials contend. For example, states a related JAMA Cardiology editorial published the same day, “The USPSTF does not comment on familial hypercholesterolemia or an LDL-C level of 190 mg/dL or higher,” yet they are covered by the ACC/AHA-multispecialty guidelines.
In addition, write the editorialists, led by Neil J. Stone, MD, Northwestern University, Chicago, “the USPSTF uses a slightly higher threshold for initiation of statin therapy” than was used in the ACC/AHA-multisociety guidelines. USPSTF, for example, calls for 10-year risk to reach 10% before recommending a statin prescription.
“One concern about the USPSTF setting the bar higher for statin initiation is that it reduces the number of young patients (age 40-50 years) at risk for premature myocardial infarction considered for treatment,” write Dr. Stone and colleagues.
That may be related to a weakness of the PCE-based decision process. “Because the PCE estimates of 10-year CV disease risk rely so heavily on age, sex, and race, use of these estimates to identify candidates for statins results in significant skewing of the population recommended for statins,” write Dr. Navar and Dr. Peterson in their JAMA editorial.
The risk enhancers in the ACC/AHA-multispecialty guidelines, about a dozen of them, compensate for that limitation to some extent. But the PCE-dominated USPSTF risk estimates will likely miss some groups that could potentially benefit from statin therapy, Dr. Peterson agreed in an interview.
For example, younger adults facing years of high LDL-cholesterol levels could easily have PCE-based 10-year risk below 10%. “Having a high LDL over a lifetime puts you at really high risk,” he said. “Young people are missed even though their longitudinal risk is high.” So, by waiting for the lofty 10% level of risk over 10 years, “we limit the use of medicine that’s pretty cheap and highly effective.”
Dose intensity, adverse events
Also at variance from the ACC/AHA-multispecialty guidelines, the USPSTF states that, “Based on available evidence, use of moderate-intensity statin therapy seems reasonable for the primary prevention of CV disease in most persons.”
The task force specifically explored whether evidence supports some use of high-intensity vs. moderate-intensity statins, Tufts University’s Dr. Wong said. “We found only one study that looked at that particular question, and it didn’t give us a strong answer.” An elevated rosuvastatin-related diabetes risk was apparent in the JUPITER trial, “but for the other studies, we did not find that association.”
Most of the studies that explored statins for reducing risk for a first stroke or myocardial infarction used a moderate-dose statin, Dr. Wong said. “So that’s what we would usually recommend.”
But, Dr. Virani writes, consistent with the ACC/AHA-multispecialty guidelines, “clinicians should consider titrating the intensity of therapy to the risk of the individual.” Persons in certain high-risk primary prevention groups, such as those with end-organ injury from diabetes or LDL cholesterol at least 190 mg/dL, “may derive further benefit from the use of high-intensity statin therapy.”
Low-intensity statins are another potential option, but “in contrast with its 2016 recommendations, the USPSTF no longer recommends use of low-intensity statins in certain situations,” observes a fourth editorial published the same day in JAMA Internal Medicine, with lead author Anand R. Habib, MD, MPhil, and senior author Rita F. Redberg, MD, MSc, both of the University of California, San Francisco. Dr. Redberg is the journal’s editor and has long expressed cautions about statin safety.
“While it is understandable that the Task Force was limited by lack of data on dosing, this change is unfortunate for patients because the frequency of adverse effects increases as the statin dose increases,” the editorial states. Although USPSTF did not find statistically significant harm from the drugs, “in clinical practice, adverse events are commonly reported with use of statins.”
It continues: “At present, there are further reasons to curb our enthusiasm about the use of statins for primary prevention of CV disease.” To illustrate, the editorial questioned primary-prevention statins’ balance of risk vs. clinically meaningful benefit, not benefit that is merely statistically significant.
“The purported benefits of statins in terms of relative risk reduction are fairly constant across baseline lipid levels and cardiovascular risk score categories for primary prevention,” the editorial states.
“Therefore, the absolute benefit for those in lower-risk categories is likely small given that their baseline absolute risk is low, while the chance of adverse effects is constant across risk categories.”
However, USPSTF states, “In pooled analyses of trial data, statin therapy was not associated with increased risk of study withdrawal due to adverse events or serious adverse events.” Nor did it find significant associations with cancers, liver enzyme abnormalities, or diabetes, including new-onset diabetes.
And, the USPSTF adds, “Evidence on the association between statins and renal or cognitive harms is very limited but does not indicate increased risk.”
USPSTF is supported by the U.S. Agency for Healthcare Research and Quality. Dr. Virani discloses receiving grants from the Department of Veterans Affairs, National Institutes of Health, and the World Heart Federation; and personal fees from the American College of Cardiology. Dr. Peterson discloses serving on the JAMA editorial board and receiving research support to his institution from Amgen, Bristol-Myers Squibb, Esperion, and Janssen; and consulting fees from Novo Nordisk, Bayer, and Novartis. Dr. Navar discloses receiving research support to her institution from Amgen, Bristol-Myers Squibb, Esperion, and Janssen; and receiving honoraria and consulting fees from AstraZeneca, Boehringer Ingelheim, Bayer, Janssen, Lilly, Novo Nordisk, Novartis, New Amsterdam, and Pfizer. Dr. Stone discloses receiving an honorarium from Knowledge to Practice, an educational company not associated with the pharmaceutical industry; disclosures for the other authors are in the report. Dr. Redberg discloses receiving research funding from the Arnold Ventures Foundation and the Greenwall Foundation.
A version of this article first appeared on Medscape.com.
FROM JAMA
Blood biomarkers predict TBI disability and mortality
, new research suggests.
In new data from the TRACK-TBI study group, high levels of glial fibrillary acidic protein (GFAP) and ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) proteins found in glial cells and neurons, respectively, correlated with death and severe injury. Investigators note that measuring these biomarkers may give a more accurate assessment of a patient’s prognosis following TBI.
This study is the “first report of the accuracy of a blood test that can be obtained rapidly on the day of injury to predict neurological recovery at 6 months after injury,” lead author Frederick Korley, MD, PhD, associate professor of emergency medicine at the University of Michigan, Ann Arbor, said in a news release.
The findings were published online in the Lancet Neurology.
Added value
The researchers measured GFAP and UCH-L1 in blood samples taken from 1,696 patients with TBI on the day of their injury, and they assessed patient recovery 6 months later.
The markers were measured using the i-STAT TBI Plasma test (Abbott Labs). The test was approved in 2021 by the U.S. Food and Drug Administration to determine which patients with mild TBI should undergo computed tomography scans.
About two-thirds of the study population were men, and the average age was 39 years. All patients were evaluated at Level I trauma centers for injuries caused primarily by traffic accidents or falls.
Six months following injury, 7% of the patients had died and 14% had an unfavorable outcome, ranging from vegetative state to severe disability requiring daily support. In addition, 67% had incomplete recovery, ranging from moderate disabilities requiring assistance outside of the home to minor disabling neurological or psychological deficits.
Day-of-injury GFAP and UCH-L1 levels had a high probability of predicting death (87% for GFAP and 89% for UCH-L1) and severe disability (86% for both GFAP and UCH-L1) at 6 months, the investigators reported.
The biomarkers were less accurate in predicting incomplete recovery (62% for GFAP and 61% for UCH-L1).
The researchers also assessed the added value of combining the blood biomarkers to current TBI prognostic models that take into account variables such as age, motor score, pupil reactivity, and CT characteristics.
In patients with a Glasgow Coma Scale (GCS) score of 3-12, adding GFAP and UCH-L1 alone or combined to each of the three International Mission for Prognosis and Analysis of Clinical Trials in TBI (IMPACT) models significantly increased their accuracy for predicting death (range, 90%-94%) and unfavorable outcome (range, 83%-89%).
In patients with milder TBI (GCS score, 13-15), adding GFAP and UCH-L1 to the UPFRONT prognostic model modestly increased accuracy for predicting incomplete recovery (69%).
‘Important’ findings
Commenting on the study, Cyrus A. Raji, MD, PhD, assistant professor of radiology and neurology, Washington University, St. Louis, said this “critical” study shows that these biomarkers can “predict key outcomes,” including mortality and severe disability. “Thus, in conjunction with clinical evaluations and related data such as neuroimaging, these tests may warrant translation to broader clinical practice, particularly in acute settings,” said Dr. Raji, who was not involved in the research.
Also weighing in, Heidi Fusco, MD, assistant director of the traumatic brain injury program at NYU Langone Rusk Rehabilitation, said the findings are “important.”
“Prognosis after brain injury often is based on the initial presentation, ongoing clinical exams, and neuroimaging; and the addition of biomarkers would contribute to creating a more objective prognostic model,” Dr. Fusco said.
She noted “it’s unclear” whether clinical hospital laboratories would be able to accommodate this type of laboratory drawing.
“It is imperative that clinicians still use the patient history [and] clinical and radiological exam when making clinical decisions for a patient and not just lab values. It would be best to incorporate the GFAP and UCH-L1 into a preexisting prognostic model,” Dr. Fusco said.
The study was funded by the U.S. National Institutes of Health, the National Institute of Neurologic Disorders and Stroke, the U.S. Department of Defense, One Mind, and U.S. Army Medical Research and Development Command. Dr. Korley reported having previously consulted for Abbott Laboratories and has received research funding from Abbott Laboratories, which makes the assays used in the study. Dr. Raji is a consultant for Brainreader ApS and Neurevolution. Dr. Fusco has reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, new research suggests.
In new data from the TRACK-TBI study group, high levels of glial fibrillary acidic protein (GFAP) and ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) proteins found in glial cells and neurons, respectively, correlated with death and severe injury. Investigators note that measuring these biomarkers may give a more accurate assessment of a patient’s prognosis following TBI.
This study is the “first report of the accuracy of a blood test that can be obtained rapidly on the day of injury to predict neurological recovery at 6 months after injury,” lead author Frederick Korley, MD, PhD, associate professor of emergency medicine at the University of Michigan, Ann Arbor, said in a news release.
The findings were published online in the Lancet Neurology.
Added value
The researchers measured GFAP and UCH-L1 in blood samples taken from 1,696 patients with TBI on the day of their injury, and they assessed patient recovery 6 months later.
The markers were measured using the i-STAT TBI Plasma test (Abbott Labs). The test was approved in 2021 by the U.S. Food and Drug Administration to determine which patients with mild TBI should undergo computed tomography scans.
About two-thirds of the study population were men, and the average age was 39 years. All patients were evaluated at Level I trauma centers for injuries caused primarily by traffic accidents or falls.
Six months following injury, 7% of the patients had died and 14% had an unfavorable outcome, ranging from vegetative state to severe disability requiring daily support. In addition, 67% had incomplete recovery, ranging from moderate disabilities requiring assistance outside of the home to minor disabling neurological or psychological deficits.
Day-of-injury GFAP and UCH-L1 levels had a high probability of predicting death (87% for GFAP and 89% for UCH-L1) and severe disability (86% for both GFAP and UCH-L1) at 6 months, the investigators reported.
The biomarkers were less accurate in predicting incomplete recovery (62% for GFAP and 61% for UCH-L1).
The researchers also assessed the added value of combining the blood biomarkers to current TBI prognostic models that take into account variables such as age, motor score, pupil reactivity, and CT characteristics.
In patients with a Glasgow Coma Scale (GCS) score of 3-12, adding GFAP and UCH-L1 alone or combined to each of the three International Mission for Prognosis and Analysis of Clinical Trials in TBI (IMPACT) models significantly increased their accuracy for predicting death (range, 90%-94%) and unfavorable outcome (range, 83%-89%).
In patients with milder TBI (GCS score, 13-15), adding GFAP and UCH-L1 to the UPFRONT prognostic model modestly increased accuracy for predicting incomplete recovery (69%).
‘Important’ findings
Commenting on the study, Cyrus A. Raji, MD, PhD, assistant professor of radiology and neurology, Washington University, St. Louis, said this “critical” study shows that these biomarkers can “predict key outcomes,” including mortality and severe disability. “Thus, in conjunction with clinical evaluations and related data such as neuroimaging, these tests may warrant translation to broader clinical practice, particularly in acute settings,” said Dr. Raji, who was not involved in the research.
Also weighing in, Heidi Fusco, MD, assistant director of the traumatic brain injury program at NYU Langone Rusk Rehabilitation, said the findings are “important.”
“Prognosis after brain injury often is based on the initial presentation, ongoing clinical exams, and neuroimaging; and the addition of biomarkers would contribute to creating a more objective prognostic model,” Dr. Fusco said.
She noted “it’s unclear” whether clinical hospital laboratories would be able to accommodate this type of laboratory drawing.
“It is imperative that clinicians still use the patient history [and] clinical and radiological exam when making clinical decisions for a patient and not just lab values. It would be best to incorporate the GFAP and UCH-L1 into a preexisting prognostic model,” Dr. Fusco said.
The study was funded by the U.S. National Institutes of Health, the National Institute of Neurologic Disorders and Stroke, the U.S. Department of Defense, One Mind, and U.S. Army Medical Research and Development Command. Dr. Korley reported having previously consulted for Abbott Laboratories and has received research funding from Abbott Laboratories, which makes the assays used in the study. Dr. Raji is a consultant for Brainreader ApS and Neurevolution. Dr. Fusco has reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, new research suggests.
In new data from the TRACK-TBI study group, high levels of glial fibrillary acidic protein (GFAP) and ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) proteins found in glial cells and neurons, respectively, correlated with death and severe injury. Investigators note that measuring these biomarkers may give a more accurate assessment of a patient’s prognosis following TBI.
This study is the “first report of the accuracy of a blood test that can be obtained rapidly on the day of injury to predict neurological recovery at 6 months after injury,” lead author Frederick Korley, MD, PhD, associate professor of emergency medicine at the University of Michigan, Ann Arbor, said in a news release.
The findings were published online in the Lancet Neurology.
Added value
The researchers measured GFAP and UCH-L1 in blood samples taken from 1,696 patients with TBI on the day of their injury, and they assessed patient recovery 6 months later.
The markers were measured using the i-STAT TBI Plasma test (Abbott Labs). The test was approved in 2021 by the U.S. Food and Drug Administration to determine which patients with mild TBI should undergo computed tomography scans.
About two-thirds of the study population were men, and the average age was 39 years. All patients were evaluated at Level I trauma centers for injuries caused primarily by traffic accidents or falls.
Six months following injury, 7% of the patients had died and 14% had an unfavorable outcome, ranging from vegetative state to severe disability requiring daily support. In addition, 67% had incomplete recovery, ranging from moderate disabilities requiring assistance outside of the home to minor disabling neurological or psychological deficits.
Day-of-injury GFAP and UCH-L1 levels had a high probability of predicting death (87% for GFAP and 89% for UCH-L1) and severe disability (86% for both GFAP and UCH-L1) at 6 months, the investigators reported.
The biomarkers were less accurate in predicting incomplete recovery (62% for GFAP and 61% for UCH-L1).
The researchers also assessed the added value of combining the blood biomarkers to current TBI prognostic models that take into account variables such as age, motor score, pupil reactivity, and CT characteristics.
In patients with a Glasgow Coma Scale (GCS) score of 3-12, adding GFAP and UCH-L1 alone or combined to each of the three International Mission for Prognosis and Analysis of Clinical Trials in TBI (IMPACT) models significantly increased their accuracy for predicting death (range, 90%-94%) and unfavorable outcome (range, 83%-89%).
In patients with milder TBI (GCS score, 13-15), adding GFAP and UCH-L1 to the UPFRONT prognostic model modestly increased accuracy for predicting incomplete recovery (69%).
‘Important’ findings
Commenting on the study, Cyrus A. Raji, MD, PhD, assistant professor of radiology and neurology, Washington University, St. Louis, said this “critical” study shows that these biomarkers can “predict key outcomes,” including mortality and severe disability. “Thus, in conjunction with clinical evaluations and related data such as neuroimaging, these tests may warrant translation to broader clinical practice, particularly in acute settings,” said Dr. Raji, who was not involved in the research.
Also weighing in, Heidi Fusco, MD, assistant director of the traumatic brain injury program at NYU Langone Rusk Rehabilitation, said the findings are “important.”
“Prognosis after brain injury often is based on the initial presentation, ongoing clinical exams, and neuroimaging; and the addition of biomarkers would contribute to creating a more objective prognostic model,” Dr. Fusco said.
She noted “it’s unclear” whether clinical hospital laboratories would be able to accommodate this type of laboratory drawing.
“It is imperative that clinicians still use the patient history [and] clinical and radiological exam when making clinical decisions for a patient and not just lab values. It would be best to incorporate the GFAP and UCH-L1 into a preexisting prognostic model,” Dr. Fusco said.
The study was funded by the U.S. National Institutes of Health, the National Institute of Neurologic Disorders and Stroke, the U.S. Department of Defense, One Mind, and U.S. Army Medical Research and Development Command. Dr. Korley reported having previously consulted for Abbott Laboratories and has received research funding from Abbott Laboratories, which makes the assays used in the study. Dr. Raji is a consultant for Brainreader ApS and Neurevolution. Dr. Fusco has reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM THE LANCET NEUROLOGY
Pfizer seeks approval for updated COVID booster
Pfizer has sent an application to the Food and Drug Administration for emergency use authorization of its updated COVID-19 booster vaccine for the fall of 2022, the company announced on Aug. 22.
The vaccine, which is adapted for the BA.4 and BA.5 Omicron variants, would be meant for ages 12 and older. If authorized by the FDA, the doses could ship as soon as September.
“Having rapidly scaled up production, we are positioned to immediately begin distribution of the bivalent Omicron BA.4/BA.5 boosters, if authorized, to help protect individuals and families as we prepare for potential fall and winter surges,” Albert Bourla, PhD, Pfizer’s chairman and CEO, said in the statement.
Earlier this year, the FDA ordered vaccine makers such as Pfizer and Moderna to update their shots to target BA.4 and BA.5, which are better at escaping immunity from earlier vaccines and previous infections.
The United States has a contract to buy 105 million of the Pfizer doses and 66 million of the Moderna doses, according to The Associated Press. Moderna is expected to file its FDA application soon as well.
The new shots target both the original spike protein on the coronavirus and the spike mutations carried by BA.4 and BA.5. For now, BA.5 is causing 89% of new infections in the United States, followed by BA.4.6 with 6.3% and BA.4 with 4.3%, according to the latest Centers for Disease Control and Prevention data.
There’s no way to tell if BA.5 will still be the dominant strain this winter or if new variant will replace it, the AP reported. But public health officials have supported the updated boosters as a way to target the most recent strains and increase immunity again.
On Aug. 15, Great Britain became the first country to authorize another one of Moderna’s updated vaccines, which adds protection against BA.1, or the original Omicron strain that became dominant in the winter of 2021-2022. European regulators are considering this shot, the AP reported, but the United States opted not to use this version since new Omicron variants have become dominant.
To approve the latest Pfizer shot, the FDA will rely on scientific testing of prior updates to the vaccine, rather than the newest boosters, to decide whether to fast-track the updated shots for fall, the AP reported. This method is like how flu vaccines are updated each year without large studies that take months.
Previously, Pfizer announced results from a study that found the earlier Omicron update significantly boosted antibodies capable of fighting the BA.1 variant and provided some protection against BA.4 and BA.5. The company’s latest FDA application contains that data and animal testing on the newest booster, the AP reported.
Pfizer will start a trial using the BA.4/BA.5 booster in coming weeks to get more data on how well the latest shot works. Moderna has begun a similar study.
The full results from these studies won’t be available before a fall booster campaign, which is why the FDA and public health officials have called for an updated shot to be ready for distribution in September.
“It’s clear that none of these vaccines are going to completely prevent infection,” Rachel Presti, MD, a researcher with the Moderna trial and an infectious diseases specialist at Washington University in St. Louis, told the AP.
But previous studies of variant booster candidates have shown that “you still get a broader immune response giving a variant booster than giving the same booster,” she said.
A version of this article first appeared on WebMD.com.
Pfizer has sent an application to the Food and Drug Administration for emergency use authorization of its updated COVID-19 booster vaccine for the fall of 2022, the company announced on Aug. 22.
The vaccine, which is adapted for the BA.4 and BA.5 Omicron variants, would be meant for ages 12 and older. If authorized by the FDA, the doses could ship as soon as September.
“Having rapidly scaled up production, we are positioned to immediately begin distribution of the bivalent Omicron BA.4/BA.5 boosters, if authorized, to help protect individuals and families as we prepare for potential fall and winter surges,” Albert Bourla, PhD, Pfizer’s chairman and CEO, said in the statement.
Earlier this year, the FDA ordered vaccine makers such as Pfizer and Moderna to update their shots to target BA.4 and BA.5, which are better at escaping immunity from earlier vaccines and previous infections.
The United States has a contract to buy 105 million of the Pfizer doses and 66 million of the Moderna doses, according to The Associated Press. Moderna is expected to file its FDA application soon as well.
The new shots target both the original spike protein on the coronavirus and the spike mutations carried by BA.4 and BA.5. For now, BA.5 is causing 89% of new infections in the United States, followed by BA.4.6 with 6.3% and BA.4 with 4.3%, according to the latest Centers for Disease Control and Prevention data.
There’s no way to tell if BA.5 will still be the dominant strain this winter or if new variant will replace it, the AP reported. But public health officials have supported the updated boosters as a way to target the most recent strains and increase immunity again.
On Aug. 15, Great Britain became the first country to authorize another one of Moderna’s updated vaccines, which adds protection against BA.1, or the original Omicron strain that became dominant in the winter of 2021-2022. European regulators are considering this shot, the AP reported, but the United States opted not to use this version since new Omicron variants have become dominant.
To approve the latest Pfizer shot, the FDA will rely on scientific testing of prior updates to the vaccine, rather than the newest boosters, to decide whether to fast-track the updated shots for fall, the AP reported. This method is like how flu vaccines are updated each year without large studies that take months.
Previously, Pfizer announced results from a study that found the earlier Omicron update significantly boosted antibodies capable of fighting the BA.1 variant and provided some protection against BA.4 and BA.5. The company’s latest FDA application contains that data and animal testing on the newest booster, the AP reported.
Pfizer will start a trial using the BA.4/BA.5 booster in coming weeks to get more data on how well the latest shot works. Moderna has begun a similar study.
The full results from these studies won’t be available before a fall booster campaign, which is why the FDA and public health officials have called for an updated shot to be ready for distribution in September.
“It’s clear that none of these vaccines are going to completely prevent infection,” Rachel Presti, MD, a researcher with the Moderna trial and an infectious diseases specialist at Washington University in St. Louis, told the AP.
But previous studies of variant booster candidates have shown that “you still get a broader immune response giving a variant booster than giving the same booster,” she said.
A version of this article first appeared on WebMD.com.
Pfizer has sent an application to the Food and Drug Administration for emergency use authorization of its updated COVID-19 booster vaccine for the fall of 2022, the company announced on Aug. 22.
The vaccine, which is adapted for the BA.4 and BA.5 Omicron variants, would be meant for ages 12 and older. If authorized by the FDA, the doses could ship as soon as September.
“Having rapidly scaled up production, we are positioned to immediately begin distribution of the bivalent Omicron BA.4/BA.5 boosters, if authorized, to help protect individuals and families as we prepare for potential fall and winter surges,” Albert Bourla, PhD, Pfizer’s chairman and CEO, said in the statement.
Earlier this year, the FDA ordered vaccine makers such as Pfizer and Moderna to update their shots to target BA.4 and BA.5, which are better at escaping immunity from earlier vaccines and previous infections.
The United States has a contract to buy 105 million of the Pfizer doses and 66 million of the Moderna doses, according to The Associated Press. Moderna is expected to file its FDA application soon as well.
The new shots target both the original spike protein on the coronavirus and the spike mutations carried by BA.4 and BA.5. For now, BA.5 is causing 89% of new infections in the United States, followed by BA.4.6 with 6.3% and BA.4 with 4.3%, according to the latest Centers for Disease Control and Prevention data.
There’s no way to tell if BA.5 will still be the dominant strain this winter or if new variant will replace it, the AP reported. But public health officials have supported the updated boosters as a way to target the most recent strains and increase immunity again.
On Aug. 15, Great Britain became the first country to authorize another one of Moderna’s updated vaccines, which adds protection against BA.1, or the original Omicron strain that became dominant in the winter of 2021-2022. European regulators are considering this shot, the AP reported, but the United States opted not to use this version since new Omicron variants have become dominant.
To approve the latest Pfizer shot, the FDA will rely on scientific testing of prior updates to the vaccine, rather than the newest boosters, to decide whether to fast-track the updated shots for fall, the AP reported. This method is like how flu vaccines are updated each year without large studies that take months.
Previously, Pfizer announced results from a study that found the earlier Omicron update significantly boosted antibodies capable of fighting the BA.1 variant and provided some protection against BA.4 and BA.5. The company’s latest FDA application contains that data and animal testing on the newest booster, the AP reported.
Pfizer will start a trial using the BA.4/BA.5 booster in coming weeks to get more data on how well the latest shot works. Moderna has begun a similar study.
The full results from these studies won’t be available before a fall booster campaign, which is why the FDA and public health officials have called for an updated shot to be ready for distribution in September.
“It’s clear that none of these vaccines are going to completely prevent infection,” Rachel Presti, MD, a researcher with the Moderna trial and an infectious diseases specialist at Washington University in St. Louis, told the AP.
But previous studies of variant booster candidates have shown that “you still get a broader immune response giving a variant booster than giving the same booster,” she said.
A version of this article first appeared on WebMD.com.
Digital therapy may ‘rewire’ the brain to improve tinnitus
, new research suggests. In a randomized controlled trial, results at 12 weeks showed patients with tinnitus reported clinically meaningful reductions in ratings of annoyance, inability to ignore, unpleasantness, and loudness after using a digital polytherapeutic app prototype that focuses on relief, relaxation, and attention-focused retraining. In addition, their improvements were significantly greater than for the control group, which received a common white noise app.
Researchers called the results “promising” for a condition that has no cure and few successful treatments. “What this therapy does is essentially rewire the brain in a way that de-emphasizes the sound of the tinnitus to a background noise that has no meaning or relevance to the listener,” lead author Grant Searchfield, PhD, associate professor of audiology at the University of Auckland, New Zealand, said in a press release.
The findings were published online in Frontiers in Neurology.
Worldwide problem
A recent study showed more than 740 million adults worldwide (nearly 15% of the population) have experienced at least one symptom of tinnitus – and about 120 million are severely affected. Tinnitus is the perception of a ringing, buzzing, whistling, or hissing noise in one or both ears when no external source of the sound is present. Often caused by damage to the auditory system, tinnitus can also be a symptom of a wide range of medical conditions and has been identified as a side effect of COVID-19 vaccination. In its most severe form, which is associated with hearing loss, tinnitus can also affect a patient’s mental, emotional, and social health.
For the current study, participants with tinnitus were randomly assigned to a popular app that uses white noise (control group, n = 30) or to the UpSilent app (n = 31). The UpSilent group received a smartphone app, Bluetooth bone conduction headphones, a Bluetooth neck pillow speaker for sleep, and written counseling materials. Participants in the control group received a widely available app called “White Noise” and in-ear wired headphones.
‘Quicker and more effective’
Both groups reported reductions in ratings of annoyance, inability to ignore, unpleasantness, and loudness at 12 weeks. But significantly more of the UpSilent group reported clinically meaningful improvement compared with the control group (65% vs. 43%, respectively; P = .049).
“Earlier trials have found white noise, goal-based counseling, goal-oriented games, and other technology-based therapies are effective for some people some of the time,” Dr. Searchfield said. “This is quicker and more effective, taking 12 weeks rather than 12 months for more individuals to gain some control,” he added.
The investigators noted that the study was not designed to determine which of the app’s functions of passive listening, active listening, or counseling contributed to symptom improvement.
The next step will be to refine the prototype and proceed to larger local and international trials with a view toward approval by the U.S. Food and Drug Administration, they reported.
The researchers hope the app will be clinically available in about 6 months.
The study was funded by Return on Science, Auckland UniServices. Dr. Searchfield is a founder and scientific officer for TrueSilence, a spinout company of the University of Auckland, and has a financial interest in TrueSilence. His coauthor has reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, new research suggests. In a randomized controlled trial, results at 12 weeks showed patients with tinnitus reported clinically meaningful reductions in ratings of annoyance, inability to ignore, unpleasantness, and loudness after using a digital polytherapeutic app prototype that focuses on relief, relaxation, and attention-focused retraining. In addition, their improvements were significantly greater than for the control group, which received a common white noise app.
Researchers called the results “promising” for a condition that has no cure and few successful treatments. “What this therapy does is essentially rewire the brain in a way that de-emphasizes the sound of the tinnitus to a background noise that has no meaning or relevance to the listener,” lead author Grant Searchfield, PhD, associate professor of audiology at the University of Auckland, New Zealand, said in a press release.
The findings were published online in Frontiers in Neurology.
Worldwide problem
A recent study showed more than 740 million adults worldwide (nearly 15% of the population) have experienced at least one symptom of tinnitus – and about 120 million are severely affected. Tinnitus is the perception of a ringing, buzzing, whistling, or hissing noise in one or both ears when no external source of the sound is present. Often caused by damage to the auditory system, tinnitus can also be a symptom of a wide range of medical conditions and has been identified as a side effect of COVID-19 vaccination. In its most severe form, which is associated with hearing loss, tinnitus can also affect a patient’s mental, emotional, and social health.
For the current study, participants with tinnitus were randomly assigned to a popular app that uses white noise (control group, n = 30) or to the UpSilent app (n = 31). The UpSilent group received a smartphone app, Bluetooth bone conduction headphones, a Bluetooth neck pillow speaker for sleep, and written counseling materials. Participants in the control group received a widely available app called “White Noise” and in-ear wired headphones.
‘Quicker and more effective’
Both groups reported reductions in ratings of annoyance, inability to ignore, unpleasantness, and loudness at 12 weeks. But significantly more of the UpSilent group reported clinically meaningful improvement compared with the control group (65% vs. 43%, respectively; P = .049).
“Earlier trials have found white noise, goal-based counseling, goal-oriented games, and other technology-based therapies are effective for some people some of the time,” Dr. Searchfield said. “This is quicker and more effective, taking 12 weeks rather than 12 months for more individuals to gain some control,” he added.
The investigators noted that the study was not designed to determine which of the app’s functions of passive listening, active listening, or counseling contributed to symptom improvement.
The next step will be to refine the prototype and proceed to larger local and international trials with a view toward approval by the U.S. Food and Drug Administration, they reported.
The researchers hope the app will be clinically available in about 6 months.
The study was funded by Return on Science, Auckland UniServices. Dr. Searchfield is a founder and scientific officer for TrueSilence, a spinout company of the University of Auckland, and has a financial interest in TrueSilence. His coauthor has reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, new research suggests. In a randomized controlled trial, results at 12 weeks showed patients with tinnitus reported clinically meaningful reductions in ratings of annoyance, inability to ignore, unpleasantness, and loudness after using a digital polytherapeutic app prototype that focuses on relief, relaxation, and attention-focused retraining. In addition, their improvements were significantly greater than for the control group, which received a common white noise app.
Researchers called the results “promising” for a condition that has no cure and few successful treatments. “What this therapy does is essentially rewire the brain in a way that de-emphasizes the sound of the tinnitus to a background noise that has no meaning or relevance to the listener,” lead author Grant Searchfield, PhD, associate professor of audiology at the University of Auckland, New Zealand, said in a press release.
The findings were published online in Frontiers in Neurology.
Worldwide problem
A recent study showed more than 740 million adults worldwide (nearly 15% of the population) have experienced at least one symptom of tinnitus – and about 120 million are severely affected. Tinnitus is the perception of a ringing, buzzing, whistling, or hissing noise in one or both ears when no external source of the sound is present. Often caused by damage to the auditory system, tinnitus can also be a symptom of a wide range of medical conditions and has been identified as a side effect of COVID-19 vaccination. In its most severe form, which is associated with hearing loss, tinnitus can also affect a patient’s mental, emotional, and social health.
For the current study, participants with tinnitus were randomly assigned to a popular app that uses white noise (control group, n = 30) or to the UpSilent app (n = 31). The UpSilent group received a smartphone app, Bluetooth bone conduction headphones, a Bluetooth neck pillow speaker for sleep, and written counseling materials. Participants in the control group received a widely available app called “White Noise” and in-ear wired headphones.
‘Quicker and more effective’
Both groups reported reductions in ratings of annoyance, inability to ignore, unpleasantness, and loudness at 12 weeks. But significantly more of the UpSilent group reported clinically meaningful improvement compared with the control group (65% vs. 43%, respectively; P = .049).
“Earlier trials have found white noise, goal-based counseling, goal-oriented games, and other technology-based therapies are effective for some people some of the time,” Dr. Searchfield said. “This is quicker and more effective, taking 12 weeks rather than 12 months for more individuals to gain some control,” he added.
The investigators noted that the study was not designed to determine which of the app’s functions of passive listening, active listening, or counseling contributed to symptom improvement.
The next step will be to refine the prototype and proceed to larger local and international trials with a view toward approval by the U.S. Food and Drug Administration, they reported.
The researchers hope the app will be clinically available in about 6 months.
The study was funded by Return on Science, Auckland UniServices. Dr. Searchfield is a founder and scientific officer for TrueSilence, a spinout company of the University of Auckland, and has a financial interest in TrueSilence. His coauthor has reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM FRONTIERS IN NEUROLOGY
Gender and Patient Satisfaction in a Veterans Health Administration Outpatient Chemotherapy Unit
Gender differences in patient satisfaction with medical care have been evaluated in multiple settings; however, studies specific to the unique population of women veterans with cancer are lacking. Women are reported to value privacy, psychosocial support, and communication to a higher degree compared with men.1 Factors affecting satisfaction include the following: discomfort in sharing treatment rooms with the opposite gender, a desire for privacy with treatment and restroom use, anatomic or illness differences, and a personal history of abuse.2-4 Regrettably, up to 1 in 3 women in the United States are victims of sexual trauma in their lifetimes, and up to 1 in 4 women in the military are victims of military sexual trauma. Incidence in both settings is suspected to be higher due to underreporting.5,6
Chemotherapy treatment units are often uniquely designed as an open space, with several patients sharing a treatment area. The design reduces isolation and facilitates quick nurse-patient access during potentially toxic treatments known to have frequent adverse effects. Data suggest that nursing staff prefer open models to facilitate quick patient assessments and interventions as needed; however, patients and families prefer private treatment rooms, especially among women patients or those receiving longer infusions.7
The Veterans Health Administration (VHA) patient population is male predominant, comprised only of 10% female patients.8 Although the proportion of female patients in the VHA is expected to rise annually to about 16% by 2043, the low percentage of female veterans will persist for the foreseeable future.8 This low percentage of female veterans is reflected in the Veterans Affairs Portland Health Care System (VAPHCS) cancer patient population and in the use of the chemotherapy infusion unit, which is used for the ambulatory treatment of veterans undergoing cancer therapy.
The VHA has previously explored gender differences in health care, such as with cardiovascular disease, transgender care, and access to mental health.9-11 However, to the best of our knowledge, no analysis has explored gender differences within the outpatient cancer treatment experience. Patient satisfaction with outpatient cancer care may be magnified in the VHA setting due to the uniquely unequal gender populations, shared treatment space design, and high incidence of sexual abuse among women veterans. Given this, we aimed to identify gender-related preferences in outpatient cancer care in our chemotherapy infusion unit.
In our study, we used the terms male and female to reflect statistical data from the literature or labeled data from the electronic health record (EHR); whereas the terms men and women were used to describe and encompass the cultural implications and context of gender.12
Methods
This study was designated as a quality improvement (QI) project by the VAPHCS research office and Institutional Review Board in accordance with VHA policies.
The VAPHCS outpatient chemotherapy infusion unit is designed with 6 rooms for chemotherapy administration. One room is a large open space with 6 chairs for patients. The other rooms are smaller with glass dividers between the rooms, and 3 chairs inside each for patients. There are 2 private bathrooms, each gender neutral. Direct patient care is provided by physicians, nurse practitioners (NPs), infusion unit nurses, and nurse coordinators. Men represent the majority of hematology and oncology physicians (13 of 20 total: 5 women fellow physicians and 2 women attending physicians), and 2 of 4 NPs. Women represent 10 of 12 infusion unit and cancer coordinator nurses. We used the VHA Computerized Patient Record System (CPRS) EHR, to create a list of veterans treated at the VAPHCS outpatient chemotherapy infusion unit for a 2-year period (January 1, 2018, to December 31, 2020).
Male and female patient lists were first generated based on CPRS categorization. We identified all female veterans treated in the ambulatory infusion unit during the study period. Male patients were then chosen at random, recording the most recent names for each year until a matched number per year compared with the female cohort was reached. Patients were recorded only once even though they had multiple infusion unit visits. Patients were excluded who were deceased, on hospice care, lost to follow-up, could not be reached by phone, refused to take the survey, had undeliverable email addresses, or lacked internet or email access.
After filing the appropriate request through the VAPHCS Institutional Review Board committee in January 2021, patient records were reviewed for demographics data, contact information, and infusion treatment history. The survey was then conducted over a 2-week period during January and February 2021. Each patient was invited by phone to complete a 25-question anonymous online survey. The survey questions were created from patient-relayed experiences, then modeled into survey questions in a format similar to other patient satisfaction questionnaires described in cancer care and gender differences.2,13,14 The survey included self-identification of gender and was multiple choice for all except 2 questions, which allowed an open-ended response (Appendix). Only 1 answer per question was permitted. Only 1 survey link was sent to each veteran who gave permission for the survey. To protect anonymity for the small patient population, we excluded those identifying as gender nonbinary or transgender.
Statistical Analysis
Patient, disease, and treatment features are separated by male and female cohorts to reflect information from the EHR (Table 1). Survey percentages were calculated to reflect the affirmative response of the question asked (Table 2). Questions with answer options of not important, minimally important, important, or very important were calculated to reflect the sum of any importance in both cohorts. Questions with answer options of never, once, often, or every time were calculated to reflect any occurrence (sum of once, often, or every time) in both patient groups. Questions with answer options of strongly agree, somewhat agree, somewhat disagree, and strongly disagree were calculated to reflect any agreement (somewhat agree and strongly agree summed together) for both groups. Comparisons between cohorts were then conducted using a Fisher exact test. A Welch t test was used to calculate the significance of the continuous variable and overall ranking of the infusion unit experience between groups.
Results
In 2020, 414 individual patients were treated at the VAPAHCS outpatient infusion unit. Of these, 23 (5.6%) were female, and 18 agreed to take the survey. After deceased and duplicate names from 2020 were removed, another 14 eligible 2019 female patients were invited and 6 agreed to participate; 6 eligible 2018 female patients were invited and 4 agreed to take the survey (Figure). Thirty female veterans were sent a survey link and 21 (70%) responses were collected. Twenty-one male 2020 patients were contacted and 18 agreed to take the survey. After removing duplicate names and deceased individuals, 17 of 21 eligible 2019 male patients and 4 of 6 eligible 2018 patients agreed to take the survey. Five additional male veterans declined the online-based survey method. In total, 39 male veterans were reached who agreed to have the survey link emailed, and 20 (51%) total responses were collected.
Most respondents answered all questions in the survey. The most frequently skipped questions included 3 questions that were contingent on a yes answer to a prior question, and 2 openended questions asking for a write-in response. Percentages for female and male respondents were adjusted for number of responses when applicable.
Thirteen (62%) female patients were aged < 65 years, while 18 (90%) of male patients were aged ≥ 65 years. Education beyond high school was reported in 20 female and 15 male respondents. Almost all treatment administered in the infusion unit was for cancer-directed treatment, with only 1 reporting a noncancer treatment (IV iron). The most common malignancy among female patients was breast cancer (n = 11, 52%); for male patients prostate cancer (n = 4, 20%) and hematologic malignancy (n = 4, 20%) were most common. Four (19%) female and 8 (40%) male respondents reported having a metastatic diagnosis. Overall patient satisfaction ranked high with an average score of 9.1 on a 10-point scale. The mean (SD) satisfaction score for female respondents was 1 point lower than that for men: 8.7 (2.2) vs 9.6 (0.6) in men (P = .11).
Eighteen (86%) women reported a history of sexual abuse or harassment compared with 2 (10%) men (P < .001). The sexual abuse assailant was a different gender for 17 of 18 female respondents and of the same gender for both male respondents. Of those with sexual abuse history, 4 women reported feeling uncomfortable around their assailant’s gender vs no men (P = .11), but this difference was not statistically significant. Six women (29%) and 2 (10%) men reported feeling uncomfortable during clinical examinations from comments made by the clinician or during treatment administration (P = .24). Six (29%) women and no men reported that they “felt uncomfortable in the infusion unit by other patients” (P = .02). Six (29%) women and no men reported feeling unable to “voice uncomfortable experiences” to the infusion unit clinician (P = .02).
Ten (48%) women and 6 (30%) men reported emotional support when receiving treatments provided by staff of the same gender (P = .34). Eight (38%) women and 4 (20%) men noted that access to treatment with the same gender was important (P = .31). Six (29%) women and 4 (20%) men indicated that access to a sex or gender-specific restroom was important (P = .72). No gender preferences were identified in the survey questions regarding importance of private treatment room access and level of emotional support when receiving treatment with others of the same malignancy. These relationships were not statistically significant.
In addition, 2 open-ended questions were asked. Seventeen women and 14 men responded. Contact the corresponding author for more information on the questions and responses.
Discussion
Overall patient satisfaction was high among the men and women veterans with cancer who received treatment in our outpatient infusion unit; however, notable gender differences existed. Three items in the survey revealed statistically significant differences in the patient experience between men and women veterans: history of sexual abuse or harassment, uncomfortable feelings among other patients, and discomfort in relaying uncomfortable feelings to a clinician. Other items in the survey did not reach statistical significance; however, we have included discussion of the findings as they may highlight important trends and be of clinical significance.
We suspect differences among genders in patient satisfaction to be related to the high incidence of sexual abuse or harassment history reported by women, much higher at 86% than the one-third to one-fourth incidence rates estimated by the existing literature for civilian or military sexual abuse in women.5,6 These high sexual abuse or harassment rates are present in a majority of women who receive cancer-directed treatment toward a gender-specific breast malignancy, surrounded predominantly among men in a shared treatment space. Together, these factors are likely key reasons behind the differences in satisfaction observed. This sentiment is expressed in our cohort, where one-fifth of women with a sexual abuse or harassment history continue to remain uncomfortable around men, and 29% of women reporting some uncomfortable feelings during their treatment experience compared with none of the men. Additionally, 6 (29%) women vs no men felt uncomfortable in reporting an uncomfortable experience with a clinician; this represents a significant barrier in providing care for these patients.
A key gender preference among women included access to shared treatment rooms with other women and that sharing a treatment space with other women resulted in feeling more emotional support during treatments. Access to gender-specific restrooms was also preferred by women more than men. Key findings in both genders were that about half of men and women valued access to a private treatment room and would derive more emotional support when surrounded by others with the same cancer.
Prior studies on gender and patient satisfaction in general medical care and cancer care have found women value privacy more than men.1-3 Wessels and colleagues performed an analysis of 386 patients with cancer in Europe and found gender to be the strongest influence in patient preferences within cancer care. Specifically, the highest statically significant association in care preferences among women included privacy, support/counseling/rehabilitation access, and decreased wait times.2 These findings were most pronounced in those with breast cancer compared with other malignancy type and highlights that malignancy type and gender predominance impact care satisfaction.
Traditionally a shared treatment space design has been used in outpatient chemotherapy units, similar to the design of the VAPHCS. However, recent data report on the patient preference for a private treatment space, which was especially prominent among women and those receiving longer infusions.7 In another study that evaluated 225 patients with cancer preferences in sharing a treatment space with those of a different sexual orientation or gender identify, differences were found. Both men and women had a similar level of comfort in sharing a treatment room with someone of a different sexual orientation; however, more women reported discomfort in sharing a treatment space with a transgender woman compared with men who felt more comfortable sharing a space with a transgender man.4 We noted a gender preference may be present to explain the difference. Within our cohort, women valued access to treatment with other women and derived more emotional support when with other women; however, we did not inquire about feelings in sharing a treatment space among transgender individuals or differing sexual orientation.
Gender differences for privacy and in shared room preferences may result from the lasting impacts of prior sexual abuse or harassment. A history of sexual abuse negatively impacts later medical care access and use.15 Those veterans who experienced sexual abuse/harrassment reported higher feelings of lack of control, vulnerability, depression, and pursued less medical care.15,16 Within cancer care, these feelings are most pronounced among women with gender-specific malignancies, such as gynecologic cancers or breast cancer. Treatment, screening, and physical examinations by clinicians who are of the same gender as the sexual abuse/harassment assailant can recreate traumatic feelings.15,16
A majority of women (n = 18, 86%) in our cohort reported a history of sexual abuse or harassment and breast malignancy was the most common cancer among women. However women represent just 5.6% of the VAPHCS infusion unit treatment population. This combination of factors may explain the reasons for women veterans’ preference for privacy during treatments, access to gender-specific restrooms, and feeling more emotional support when surrounded by other women. Strategies to help patients with a history of abuse have been described and include discussions from the clinician asking about abuse history, allowing time for the patient to express fears with an examination or test, and training on how to deliver sensitive care for those with trauma.17,18
Quality Improvement
Project In the VAPHCS infusion unit, several low-cost interventions have been undertaken as a result of our survey findings. We presented our survey data to the VAPHCS Cancer Committee, accredited through the national American College of Surgeons Commission on Cancer. The committee awarded support for a yearlong QI project, including a formal framework of quarterly multidisciplinary meetings to discuss project updates, challenges, and resources. The QI project centers on education to raise awareness of survey results as well as specific interventions for improvement.
Education efforts have been applied through multiple department-wide emails, in-person education to our chemotherapy unit staff, abstract submission to national oncology conferences, and grand rounds department presentations at VAPHCS and at other VHA-affiliated university programs. Additionally, education to clinicians with specific contact information for psychology and women’s health to support mental health, trauma, and sexual abuse histories has been given to each clinician who cares for veterans in the chemotherapy unit.
We also have implemented a mandatory cancer care navigation consultation for all women veterans who have a new cancer or infusion need. The cancer care navigator has received specialized training in sensitive history-taking and provides women veterans with a direct number to reach the cancer care navigation nurse. Cancer care navigation also provides a continuum of support and referral access for psychosocial needs as indicated between infusion or health care visits. Our hope is that these resources may help offset the sentiment reflected in our cohort of women feeling unable to voice concerns to a clinician.
Other interventions underway include offering designated scheduling time each week to women so they can receive infusions in an area with other women. This may help mitigate the finding that women veterans felt more uncomfortable around other patients during infusion treatments compared with how men felt in the chemotherapy unit. We also have implemented gender-specific restrooms labeled with a sign on each bathroom door so men and women can have access to a designated restroom. Offering private or semiprivate treatment rooms is currently limited by space and capacity; however, these may offer the greatest opportunity to improve patient satisfaction, especially among women veterans. Working with the support of the VAPHCS Cancer Committee, we aim to reevaluate the impact of the education and QI efforts on gender differences and patient satisfaction at completion of the 1-year award.
Limitations
Limitations to our study include the overall small sample size. This is due to the combination of the low number of women treated at VAPHCS and many with advanced cancer who, unfortunately, have a limited overall survival and hinders accrual of a larger sample size. Other limitations included age as a possible confounder in our findings, with women representing a younger demographic compared with men. We did not collect responses on duration of infusion time, which also may impact overall satisfaction and patient experience. We also acknowledge that biologic male or female sex may not correspond to a specific individual’s gender. Use of CPRS to obtain a matched number of male and female patients through random selection relied on labeled data from the EHR. This potentially may have excluded male patients who identify as another gender that would have been captured on the anonymous survey.
Last, we restricted survey responses to online only, which excluded a small percentage who declined this approach.
Conclusions
Our findings may have broad applications to other VHA facilities and other cancer-directed treatment centers where the patient demographic and open shared infusion unit design may be similar. The study also may serve as a model of survey design and implementation from which other centers may consider improving patient satisfaction. We hope these survey results and interventions can provide insight and be used to improve patient satisfaction among all cancer patients at infusion units serving veterans and nonveterans.
Acknowledgments
We are very thankful to our cancer patients who took the time to take the survey. We also are very grateful to the VHA infusion unit nurses, staff, nurse practitioners, and physicians who have embraced this project and welcomed any changes that may positively impact treatment of veterans. Also, thank you to Tia Kohs for statistical support and Sophie West for gender discussions. Last, we specifically thank Barbara, for her pursuit of better care for women and for all veterans.
1. Clarke SA, Booth L, Velikova G, Hewison J. Social support: gender differences in cancer patients in the United Kingdom. Cancer Nurs. 2006;29(1):66-72. doi:10.1097/00002820-200601000-00012
2. Wessels H, de Graeff A, Wynia K, et al. Gender-related needs and preferences in cancer care indicate the need for an individualized approach to cancer patients. Oncologist. 2010;15(6):648-655. doi:10.1634/theoncologist.2009-0337
3. Hartigan SM, Bonnet K, Chisholm L, et al. Why do women not use the bathroom? Women’s attitudes and beliefs on using public restrooms. Int J Environ Res Public Health. 2020;17(6):2053. doi:10.3390/ijerph17062053
4. Alexander K, Walters CB, Banerjee SC. Oncology patients’ preferences regarding sexual orientation and gender identity (SOGI) disclosure and room sharing sharing. Patient Educ Couns. 2020;103(5):1041-1048. doi:10.1016/j.pec.2019.12.006
5. Centers for Disease Control and Prevention. Facts about sexual violence. Updated July 5, 2022. Accessed July 13, 2022. https://www.cdc.gov/injury/features /sexual-violence/index.html
6. US Department of Veterans Affairs. Military sexual trauma. Updated May 16, 2022. Accessed July 13, 2022. https:// www.mentalhealth.va.gov/mentalhealth/msthome/index.asp
7. Wang Z, Pukszta M. Private Rooms, Semi-open areas, or open areas for chemotherapy care: perspectives of cancer patients, families, and nursing staff. HERD. 2018;11(3):94- 108. doi:10.1177/1937586718758445
8. US Department of Veterans Affairs, National Center for Veterans Analysis and Statistics. Women veterans report: the past, present, and future of women veterans. Accessed July 13, 2022. https://www.va.gov/vetdata /docs/specialreports/women_veterans_2015_final.pdf
9. Driscoll MA, Higgins DM, Seng EK, et al. Trauma, social support, family conflict, and chronic pain in recent service veterans: does gender matter? Pain Med. 2015;16(6):1101- 1111. doi:10.1111/pme.12744
10. Fox AB, Meyer EC, Vogt D. Attitudes about the VA healthcare setting, mental illness, and mental health treatment and their relationship with VA mental health service use among female and male OEF/OIF veterans. Psychol Serv. 2015;12(1):49-58. doi:10.1037/a0038269
11. Virani SS, Woodard LD, Ramsey DJ, et al. Gender disparities in evidence-based statin therapy in patients with cardiovascular disease. Am J Cardiol. 2015;115(1):21-26. doi:10.1016/j.amjcard.2014.09.041
12. Tseng J. Sex, gender, and why the differences matter. Virtual Mentor. 2008;10(7):427-428. doi:10.1001/virtualmentor.2008.10.7.fred1-0807
13. Booij JC, Zegers M, Evers PMPJ, Hendricks M, Delnoij DMJ, Rademakers JJDJM. Improving cancer patient care: development of a generic cancer consumer quality index questionnaire for cancer patients. BMC Cancer. 2013;13(203). doi:10.1186/1471-2407-13-203
14. Meropol NJ, Egleston BL, Buzaglo JS, et al. Cancer patient preferences for quality and length of life. Cancer. 2008;113(12):3459-3466. doi:10.1002/cncr.23968 1
5. Schnur JB, Dillon MJ, Goldsmith RE, Montgomery GH. Cancer treatment experiences among survivors of childhood sexual abuse: a qualitative investigation of triggers and reactions to cumulative trauma. Palliat Support Care. 2018;16(6):767-776. doi:10.1017/S147895151700075X
16. Cadman L, Waller J, Ashdown-Barr L, Szarewski A. Barriers to cervical screening in women who have experienced sexual abuse: an exploratory study. J Fam Plann Reprod Health Care. 2012;38(4):214-220. doi:10.1136/jfprhc-2012-100378
17. Kelly S. The effects of childhood sexual abuse on women’s lives and their attitudes to cervical screening. J Fam Plann Reprod Health Care. 2012;38(4):212-213. doi:10.1136/jfprhc-2012-100418
18. McCloskey LA, Lichter E, Williams C, Gerber M, Wittenberg E, Ganz M. Assessing intimate partner violence in health care settings leads to women’s receipt of interventions and improved health. Public Health Rep. 2006;121(4):435-444. doi:10.1177/003335490612100412
Gender differences in patient satisfaction with medical care have been evaluated in multiple settings; however, studies specific to the unique population of women veterans with cancer are lacking. Women are reported to value privacy, psychosocial support, and communication to a higher degree compared with men.1 Factors affecting satisfaction include the following: discomfort in sharing treatment rooms with the opposite gender, a desire for privacy with treatment and restroom use, anatomic or illness differences, and a personal history of abuse.2-4 Regrettably, up to 1 in 3 women in the United States are victims of sexual trauma in their lifetimes, and up to 1 in 4 women in the military are victims of military sexual trauma. Incidence in both settings is suspected to be higher due to underreporting.5,6
Chemotherapy treatment units are often uniquely designed as an open space, with several patients sharing a treatment area. The design reduces isolation and facilitates quick nurse-patient access during potentially toxic treatments known to have frequent adverse effects. Data suggest that nursing staff prefer open models to facilitate quick patient assessments and interventions as needed; however, patients and families prefer private treatment rooms, especially among women patients or those receiving longer infusions.7
The Veterans Health Administration (VHA) patient population is male predominant, comprised only of 10% female patients.8 Although the proportion of female patients in the VHA is expected to rise annually to about 16% by 2043, the low percentage of female veterans will persist for the foreseeable future.8 This low percentage of female veterans is reflected in the Veterans Affairs Portland Health Care System (VAPHCS) cancer patient population and in the use of the chemotherapy infusion unit, which is used for the ambulatory treatment of veterans undergoing cancer therapy.
The VHA has previously explored gender differences in health care, such as with cardiovascular disease, transgender care, and access to mental health.9-11 However, to the best of our knowledge, no analysis has explored gender differences within the outpatient cancer treatment experience. Patient satisfaction with outpatient cancer care may be magnified in the VHA setting due to the uniquely unequal gender populations, shared treatment space design, and high incidence of sexual abuse among women veterans. Given this, we aimed to identify gender-related preferences in outpatient cancer care in our chemotherapy infusion unit.
In our study, we used the terms male and female to reflect statistical data from the literature or labeled data from the electronic health record (EHR); whereas the terms men and women were used to describe and encompass the cultural implications and context of gender.12
Methods
This study was designated as a quality improvement (QI) project by the VAPHCS research office and Institutional Review Board in accordance with VHA policies.
The VAPHCS outpatient chemotherapy infusion unit is designed with 6 rooms for chemotherapy administration. One room is a large open space with 6 chairs for patients. The other rooms are smaller with glass dividers between the rooms, and 3 chairs inside each for patients. There are 2 private bathrooms, each gender neutral. Direct patient care is provided by physicians, nurse practitioners (NPs), infusion unit nurses, and nurse coordinators. Men represent the majority of hematology and oncology physicians (13 of 20 total: 5 women fellow physicians and 2 women attending physicians), and 2 of 4 NPs. Women represent 10 of 12 infusion unit and cancer coordinator nurses. We used the VHA Computerized Patient Record System (CPRS) EHR, to create a list of veterans treated at the VAPHCS outpatient chemotherapy infusion unit for a 2-year period (January 1, 2018, to December 31, 2020).
Male and female patient lists were first generated based on CPRS categorization. We identified all female veterans treated in the ambulatory infusion unit during the study period. Male patients were then chosen at random, recording the most recent names for each year until a matched number per year compared with the female cohort was reached. Patients were recorded only once even though they had multiple infusion unit visits. Patients were excluded who were deceased, on hospice care, lost to follow-up, could not be reached by phone, refused to take the survey, had undeliverable email addresses, or lacked internet or email access.
After filing the appropriate request through the VAPHCS Institutional Review Board committee in January 2021, patient records were reviewed for demographics data, contact information, and infusion treatment history. The survey was then conducted over a 2-week period during January and February 2021. Each patient was invited by phone to complete a 25-question anonymous online survey. The survey questions were created from patient-relayed experiences, then modeled into survey questions in a format similar to other patient satisfaction questionnaires described in cancer care and gender differences.2,13,14 The survey included self-identification of gender and was multiple choice for all except 2 questions, which allowed an open-ended response (Appendix). Only 1 answer per question was permitted. Only 1 survey link was sent to each veteran who gave permission for the survey. To protect anonymity for the small patient population, we excluded those identifying as gender nonbinary or transgender.
Statistical Analysis
Patient, disease, and treatment features are separated by male and female cohorts to reflect information from the EHR (Table 1). Survey percentages were calculated to reflect the affirmative response of the question asked (Table 2). Questions with answer options of not important, minimally important, important, or very important were calculated to reflect the sum of any importance in both cohorts. Questions with answer options of never, once, often, or every time were calculated to reflect any occurrence (sum of once, often, or every time) in both patient groups. Questions with answer options of strongly agree, somewhat agree, somewhat disagree, and strongly disagree were calculated to reflect any agreement (somewhat agree and strongly agree summed together) for both groups. Comparisons between cohorts were then conducted using a Fisher exact test. A Welch t test was used to calculate the significance of the continuous variable and overall ranking of the infusion unit experience between groups.
Results
In 2020, 414 individual patients were treated at the VAPAHCS outpatient infusion unit. Of these, 23 (5.6%) were female, and 18 agreed to take the survey. After deceased and duplicate names from 2020 were removed, another 14 eligible 2019 female patients were invited and 6 agreed to participate; 6 eligible 2018 female patients were invited and 4 agreed to take the survey (Figure). Thirty female veterans were sent a survey link and 21 (70%) responses were collected. Twenty-one male 2020 patients were contacted and 18 agreed to take the survey. After removing duplicate names and deceased individuals, 17 of 21 eligible 2019 male patients and 4 of 6 eligible 2018 patients agreed to take the survey. Five additional male veterans declined the online-based survey method. In total, 39 male veterans were reached who agreed to have the survey link emailed, and 20 (51%) total responses were collected.
Most respondents answered all questions in the survey. The most frequently skipped questions included 3 questions that were contingent on a yes answer to a prior question, and 2 openended questions asking for a write-in response. Percentages for female and male respondents were adjusted for number of responses when applicable.
Thirteen (62%) female patients were aged < 65 years, while 18 (90%) of male patients were aged ≥ 65 years. Education beyond high school was reported in 20 female and 15 male respondents. Almost all treatment administered in the infusion unit was for cancer-directed treatment, with only 1 reporting a noncancer treatment (IV iron). The most common malignancy among female patients was breast cancer (n = 11, 52%); for male patients prostate cancer (n = 4, 20%) and hematologic malignancy (n = 4, 20%) were most common. Four (19%) female and 8 (40%) male respondents reported having a metastatic diagnosis. Overall patient satisfaction ranked high with an average score of 9.1 on a 10-point scale. The mean (SD) satisfaction score for female respondents was 1 point lower than that for men: 8.7 (2.2) vs 9.6 (0.6) in men (P = .11).
Eighteen (86%) women reported a history of sexual abuse or harassment compared with 2 (10%) men (P < .001). The sexual abuse assailant was a different gender for 17 of 18 female respondents and of the same gender for both male respondents. Of those with sexual abuse history, 4 women reported feeling uncomfortable around their assailant’s gender vs no men (P = .11), but this difference was not statistically significant. Six women (29%) and 2 (10%) men reported feeling uncomfortable during clinical examinations from comments made by the clinician or during treatment administration (P = .24). Six (29%) women and no men reported that they “felt uncomfortable in the infusion unit by other patients” (P = .02). Six (29%) women and no men reported feeling unable to “voice uncomfortable experiences” to the infusion unit clinician (P = .02).
Ten (48%) women and 6 (30%) men reported emotional support when receiving treatments provided by staff of the same gender (P = .34). Eight (38%) women and 4 (20%) men noted that access to treatment with the same gender was important (P = .31). Six (29%) women and 4 (20%) men indicated that access to a sex or gender-specific restroom was important (P = .72). No gender preferences were identified in the survey questions regarding importance of private treatment room access and level of emotional support when receiving treatment with others of the same malignancy. These relationships were not statistically significant.
In addition, 2 open-ended questions were asked. Seventeen women and 14 men responded. Contact the corresponding author for more information on the questions and responses.
Discussion
Overall patient satisfaction was high among the men and women veterans with cancer who received treatment in our outpatient infusion unit; however, notable gender differences existed. Three items in the survey revealed statistically significant differences in the patient experience between men and women veterans: history of sexual abuse or harassment, uncomfortable feelings among other patients, and discomfort in relaying uncomfortable feelings to a clinician. Other items in the survey did not reach statistical significance; however, we have included discussion of the findings as they may highlight important trends and be of clinical significance.
We suspect differences among genders in patient satisfaction to be related to the high incidence of sexual abuse or harassment history reported by women, much higher at 86% than the one-third to one-fourth incidence rates estimated by the existing literature for civilian or military sexual abuse in women.5,6 These high sexual abuse or harassment rates are present in a majority of women who receive cancer-directed treatment toward a gender-specific breast malignancy, surrounded predominantly among men in a shared treatment space. Together, these factors are likely key reasons behind the differences in satisfaction observed. This sentiment is expressed in our cohort, where one-fifth of women with a sexual abuse or harassment history continue to remain uncomfortable around men, and 29% of women reporting some uncomfortable feelings during their treatment experience compared with none of the men. Additionally, 6 (29%) women vs no men felt uncomfortable in reporting an uncomfortable experience with a clinician; this represents a significant barrier in providing care for these patients.
A key gender preference among women included access to shared treatment rooms with other women and that sharing a treatment space with other women resulted in feeling more emotional support during treatments. Access to gender-specific restrooms was also preferred by women more than men. Key findings in both genders were that about half of men and women valued access to a private treatment room and would derive more emotional support when surrounded by others with the same cancer.
Prior studies on gender and patient satisfaction in general medical care and cancer care have found women value privacy more than men.1-3 Wessels and colleagues performed an analysis of 386 patients with cancer in Europe and found gender to be the strongest influence in patient preferences within cancer care. Specifically, the highest statically significant association in care preferences among women included privacy, support/counseling/rehabilitation access, and decreased wait times.2 These findings were most pronounced in those with breast cancer compared with other malignancy type and highlights that malignancy type and gender predominance impact care satisfaction.
Traditionally a shared treatment space design has been used in outpatient chemotherapy units, similar to the design of the VAPHCS. However, recent data report on the patient preference for a private treatment space, which was especially prominent among women and those receiving longer infusions.7 In another study that evaluated 225 patients with cancer preferences in sharing a treatment space with those of a different sexual orientation or gender identify, differences were found. Both men and women had a similar level of comfort in sharing a treatment room with someone of a different sexual orientation; however, more women reported discomfort in sharing a treatment space with a transgender woman compared with men who felt more comfortable sharing a space with a transgender man.4 We noted a gender preference may be present to explain the difference. Within our cohort, women valued access to treatment with other women and derived more emotional support when with other women; however, we did not inquire about feelings in sharing a treatment space among transgender individuals or differing sexual orientation.
Gender differences for privacy and in shared room preferences may result from the lasting impacts of prior sexual abuse or harassment. A history of sexual abuse negatively impacts later medical care access and use.15 Those veterans who experienced sexual abuse/harrassment reported higher feelings of lack of control, vulnerability, depression, and pursued less medical care.15,16 Within cancer care, these feelings are most pronounced among women with gender-specific malignancies, such as gynecologic cancers or breast cancer. Treatment, screening, and physical examinations by clinicians who are of the same gender as the sexual abuse/harassment assailant can recreate traumatic feelings.15,16
A majority of women (n = 18, 86%) in our cohort reported a history of sexual abuse or harassment and breast malignancy was the most common cancer among women. However women represent just 5.6% of the VAPHCS infusion unit treatment population. This combination of factors may explain the reasons for women veterans’ preference for privacy during treatments, access to gender-specific restrooms, and feeling more emotional support when surrounded by other women. Strategies to help patients with a history of abuse have been described and include discussions from the clinician asking about abuse history, allowing time for the patient to express fears with an examination or test, and training on how to deliver sensitive care for those with trauma.17,18
Quality Improvement
Project In the VAPHCS infusion unit, several low-cost interventions have been undertaken as a result of our survey findings. We presented our survey data to the VAPHCS Cancer Committee, accredited through the national American College of Surgeons Commission on Cancer. The committee awarded support for a yearlong QI project, including a formal framework of quarterly multidisciplinary meetings to discuss project updates, challenges, and resources. The QI project centers on education to raise awareness of survey results as well as specific interventions for improvement.
Education efforts have been applied through multiple department-wide emails, in-person education to our chemotherapy unit staff, abstract submission to national oncology conferences, and grand rounds department presentations at VAPHCS and at other VHA-affiliated university programs. Additionally, education to clinicians with specific contact information for psychology and women’s health to support mental health, trauma, and sexual abuse histories has been given to each clinician who cares for veterans in the chemotherapy unit.
We also have implemented a mandatory cancer care navigation consultation for all women veterans who have a new cancer or infusion need. The cancer care navigator has received specialized training in sensitive history-taking and provides women veterans with a direct number to reach the cancer care navigation nurse. Cancer care navigation also provides a continuum of support and referral access for psychosocial needs as indicated between infusion or health care visits. Our hope is that these resources may help offset the sentiment reflected in our cohort of women feeling unable to voice concerns to a clinician.
Other interventions underway include offering designated scheduling time each week to women so they can receive infusions in an area with other women. This may help mitigate the finding that women veterans felt more uncomfortable around other patients during infusion treatments compared with how men felt in the chemotherapy unit. We also have implemented gender-specific restrooms labeled with a sign on each bathroom door so men and women can have access to a designated restroom. Offering private or semiprivate treatment rooms is currently limited by space and capacity; however, these may offer the greatest opportunity to improve patient satisfaction, especially among women veterans. Working with the support of the VAPHCS Cancer Committee, we aim to reevaluate the impact of the education and QI efforts on gender differences and patient satisfaction at completion of the 1-year award.
Limitations
Limitations to our study include the overall small sample size. This is due to the combination of the low number of women treated at VAPHCS and many with advanced cancer who, unfortunately, have a limited overall survival and hinders accrual of a larger sample size. Other limitations included age as a possible confounder in our findings, with women representing a younger demographic compared with men. We did not collect responses on duration of infusion time, which also may impact overall satisfaction and patient experience. We also acknowledge that biologic male or female sex may not correspond to a specific individual’s gender. Use of CPRS to obtain a matched number of male and female patients through random selection relied on labeled data from the EHR. This potentially may have excluded male patients who identify as another gender that would have been captured on the anonymous survey.
Last, we restricted survey responses to online only, which excluded a small percentage who declined this approach.
Conclusions
Our findings may have broad applications to other VHA facilities and other cancer-directed treatment centers where the patient demographic and open shared infusion unit design may be similar. The study also may serve as a model of survey design and implementation from which other centers may consider improving patient satisfaction. We hope these survey results and interventions can provide insight and be used to improve patient satisfaction among all cancer patients at infusion units serving veterans and nonveterans.
Acknowledgments
We are very thankful to our cancer patients who took the time to take the survey. We also are very grateful to the VHA infusion unit nurses, staff, nurse practitioners, and physicians who have embraced this project and welcomed any changes that may positively impact treatment of veterans. Also, thank you to Tia Kohs for statistical support and Sophie West for gender discussions. Last, we specifically thank Barbara, for her pursuit of better care for women and for all veterans.
Gender differences in patient satisfaction with medical care have been evaluated in multiple settings; however, studies specific to the unique population of women veterans with cancer are lacking. Women are reported to value privacy, psychosocial support, and communication to a higher degree compared with men.1 Factors affecting satisfaction include the following: discomfort in sharing treatment rooms with the opposite gender, a desire for privacy with treatment and restroom use, anatomic or illness differences, and a personal history of abuse.2-4 Regrettably, up to 1 in 3 women in the United States are victims of sexual trauma in their lifetimes, and up to 1 in 4 women in the military are victims of military sexual trauma. Incidence in both settings is suspected to be higher due to underreporting.5,6
Chemotherapy treatment units are often uniquely designed as an open space, with several patients sharing a treatment area. The design reduces isolation and facilitates quick nurse-patient access during potentially toxic treatments known to have frequent adverse effects. Data suggest that nursing staff prefer open models to facilitate quick patient assessments and interventions as needed; however, patients and families prefer private treatment rooms, especially among women patients or those receiving longer infusions.7
The Veterans Health Administration (VHA) patient population is male predominant, comprised only of 10% female patients.8 Although the proportion of female patients in the VHA is expected to rise annually to about 16% by 2043, the low percentage of female veterans will persist for the foreseeable future.8 This low percentage of female veterans is reflected in the Veterans Affairs Portland Health Care System (VAPHCS) cancer patient population and in the use of the chemotherapy infusion unit, which is used for the ambulatory treatment of veterans undergoing cancer therapy.
The VHA has previously explored gender differences in health care, such as with cardiovascular disease, transgender care, and access to mental health.9-11 However, to the best of our knowledge, no analysis has explored gender differences within the outpatient cancer treatment experience. Patient satisfaction with outpatient cancer care may be magnified in the VHA setting due to the uniquely unequal gender populations, shared treatment space design, and high incidence of sexual abuse among women veterans. Given this, we aimed to identify gender-related preferences in outpatient cancer care in our chemotherapy infusion unit.
In our study, we used the terms male and female to reflect statistical data from the literature or labeled data from the electronic health record (EHR); whereas the terms men and women were used to describe and encompass the cultural implications and context of gender.12
Methods
This study was designated as a quality improvement (QI) project by the VAPHCS research office and Institutional Review Board in accordance with VHA policies.
The VAPHCS outpatient chemotherapy infusion unit is designed with 6 rooms for chemotherapy administration. One room is a large open space with 6 chairs for patients. The other rooms are smaller with glass dividers between the rooms, and 3 chairs inside each for patients. There are 2 private bathrooms, each gender neutral. Direct patient care is provided by physicians, nurse practitioners (NPs), infusion unit nurses, and nurse coordinators. Men represent the majority of hematology and oncology physicians (13 of 20 total: 5 women fellow physicians and 2 women attending physicians), and 2 of 4 NPs. Women represent 10 of 12 infusion unit and cancer coordinator nurses. We used the VHA Computerized Patient Record System (CPRS) EHR, to create a list of veterans treated at the VAPHCS outpatient chemotherapy infusion unit for a 2-year period (January 1, 2018, to December 31, 2020).
Male and female patient lists were first generated based on CPRS categorization. We identified all female veterans treated in the ambulatory infusion unit during the study period. Male patients were then chosen at random, recording the most recent names for each year until a matched number per year compared with the female cohort was reached. Patients were recorded only once even though they had multiple infusion unit visits. Patients were excluded who were deceased, on hospice care, lost to follow-up, could not be reached by phone, refused to take the survey, had undeliverable email addresses, or lacked internet or email access.
After filing the appropriate request through the VAPHCS Institutional Review Board committee in January 2021, patient records were reviewed for demographics data, contact information, and infusion treatment history. The survey was then conducted over a 2-week period during January and February 2021. Each patient was invited by phone to complete a 25-question anonymous online survey. The survey questions were created from patient-relayed experiences, then modeled into survey questions in a format similar to other patient satisfaction questionnaires described in cancer care and gender differences.2,13,14 The survey included self-identification of gender and was multiple choice for all except 2 questions, which allowed an open-ended response (Appendix). Only 1 answer per question was permitted. Only 1 survey link was sent to each veteran who gave permission for the survey. To protect anonymity for the small patient population, we excluded those identifying as gender nonbinary or transgender.
Statistical Analysis
Patient, disease, and treatment features are separated by male and female cohorts to reflect information from the EHR (Table 1). Survey percentages were calculated to reflect the affirmative response of the question asked (Table 2). Questions with answer options of not important, minimally important, important, or very important were calculated to reflect the sum of any importance in both cohorts. Questions with answer options of never, once, often, or every time were calculated to reflect any occurrence (sum of once, often, or every time) in both patient groups. Questions with answer options of strongly agree, somewhat agree, somewhat disagree, and strongly disagree were calculated to reflect any agreement (somewhat agree and strongly agree summed together) for both groups. Comparisons between cohorts were then conducted using a Fisher exact test. A Welch t test was used to calculate the significance of the continuous variable and overall ranking of the infusion unit experience between groups.
Results
In 2020, 414 individual patients were treated at the VAPAHCS outpatient infusion unit. Of these, 23 (5.6%) were female, and 18 agreed to take the survey. After deceased and duplicate names from 2020 were removed, another 14 eligible 2019 female patients were invited and 6 agreed to participate; 6 eligible 2018 female patients were invited and 4 agreed to take the survey (Figure). Thirty female veterans were sent a survey link and 21 (70%) responses were collected. Twenty-one male 2020 patients were contacted and 18 agreed to take the survey. After removing duplicate names and deceased individuals, 17 of 21 eligible 2019 male patients and 4 of 6 eligible 2018 patients agreed to take the survey. Five additional male veterans declined the online-based survey method. In total, 39 male veterans were reached who agreed to have the survey link emailed, and 20 (51%) total responses were collected.
Most respondents answered all questions in the survey. The most frequently skipped questions included 3 questions that were contingent on a yes answer to a prior question, and 2 openended questions asking for a write-in response. Percentages for female and male respondents were adjusted for number of responses when applicable.
Thirteen (62%) female patients were aged < 65 years, while 18 (90%) of male patients were aged ≥ 65 years. Education beyond high school was reported in 20 female and 15 male respondents. Almost all treatment administered in the infusion unit was for cancer-directed treatment, with only 1 reporting a noncancer treatment (IV iron). The most common malignancy among female patients was breast cancer (n = 11, 52%); for male patients prostate cancer (n = 4, 20%) and hematologic malignancy (n = 4, 20%) were most common. Four (19%) female and 8 (40%) male respondents reported having a metastatic diagnosis. Overall patient satisfaction ranked high with an average score of 9.1 on a 10-point scale. The mean (SD) satisfaction score for female respondents was 1 point lower than that for men: 8.7 (2.2) vs 9.6 (0.6) in men (P = .11).
Eighteen (86%) women reported a history of sexual abuse or harassment compared with 2 (10%) men (P < .001). The sexual abuse assailant was a different gender for 17 of 18 female respondents and of the same gender for both male respondents. Of those with sexual abuse history, 4 women reported feeling uncomfortable around their assailant’s gender vs no men (P = .11), but this difference was not statistically significant. Six women (29%) and 2 (10%) men reported feeling uncomfortable during clinical examinations from comments made by the clinician or during treatment administration (P = .24). Six (29%) women and no men reported that they “felt uncomfortable in the infusion unit by other patients” (P = .02). Six (29%) women and no men reported feeling unable to “voice uncomfortable experiences” to the infusion unit clinician (P = .02).
Ten (48%) women and 6 (30%) men reported emotional support when receiving treatments provided by staff of the same gender (P = .34). Eight (38%) women and 4 (20%) men noted that access to treatment with the same gender was important (P = .31). Six (29%) women and 4 (20%) men indicated that access to a sex or gender-specific restroom was important (P = .72). No gender preferences were identified in the survey questions regarding importance of private treatment room access and level of emotional support when receiving treatment with others of the same malignancy. These relationships were not statistically significant.
In addition, 2 open-ended questions were asked. Seventeen women and 14 men responded. Contact the corresponding author for more information on the questions and responses.
Discussion
Overall patient satisfaction was high among the men and women veterans with cancer who received treatment in our outpatient infusion unit; however, notable gender differences existed. Three items in the survey revealed statistically significant differences in the patient experience between men and women veterans: history of sexual abuse or harassment, uncomfortable feelings among other patients, and discomfort in relaying uncomfortable feelings to a clinician. Other items in the survey did not reach statistical significance; however, we have included discussion of the findings as they may highlight important trends and be of clinical significance.
We suspect differences among genders in patient satisfaction to be related to the high incidence of sexual abuse or harassment history reported by women, much higher at 86% than the one-third to one-fourth incidence rates estimated by the existing literature for civilian or military sexual abuse in women.5,6 These high sexual abuse or harassment rates are present in a majority of women who receive cancer-directed treatment toward a gender-specific breast malignancy, surrounded predominantly among men in a shared treatment space. Together, these factors are likely key reasons behind the differences in satisfaction observed. This sentiment is expressed in our cohort, where one-fifth of women with a sexual abuse or harassment history continue to remain uncomfortable around men, and 29% of women reporting some uncomfortable feelings during their treatment experience compared with none of the men. Additionally, 6 (29%) women vs no men felt uncomfortable in reporting an uncomfortable experience with a clinician; this represents a significant barrier in providing care for these patients.
A key gender preference among women included access to shared treatment rooms with other women and that sharing a treatment space with other women resulted in feeling more emotional support during treatments. Access to gender-specific restrooms was also preferred by women more than men. Key findings in both genders were that about half of men and women valued access to a private treatment room and would derive more emotional support when surrounded by others with the same cancer.
Prior studies on gender and patient satisfaction in general medical care and cancer care have found women value privacy more than men.1-3 Wessels and colleagues performed an analysis of 386 patients with cancer in Europe and found gender to be the strongest influence in patient preferences within cancer care. Specifically, the highest statically significant association in care preferences among women included privacy, support/counseling/rehabilitation access, and decreased wait times.2 These findings were most pronounced in those with breast cancer compared with other malignancy type and highlights that malignancy type and gender predominance impact care satisfaction.
Traditionally a shared treatment space design has been used in outpatient chemotherapy units, similar to the design of the VAPHCS. However, recent data report on the patient preference for a private treatment space, which was especially prominent among women and those receiving longer infusions.7 In another study that evaluated 225 patients with cancer preferences in sharing a treatment space with those of a different sexual orientation or gender identify, differences were found. Both men and women had a similar level of comfort in sharing a treatment room with someone of a different sexual orientation; however, more women reported discomfort in sharing a treatment space with a transgender woman compared with men who felt more comfortable sharing a space with a transgender man.4 We noted a gender preference may be present to explain the difference. Within our cohort, women valued access to treatment with other women and derived more emotional support when with other women; however, we did not inquire about feelings in sharing a treatment space among transgender individuals or differing sexual orientation.
Gender differences for privacy and in shared room preferences may result from the lasting impacts of prior sexual abuse or harassment. A history of sexual abuse negatively impacts later medical care access and use.15 Those veterans who experienced sexual abuse/harrassment reported higher feelings of lack of control, vulnerability, depression, and pursued less medical care.15,16 Within cancer care, these feelings are most pronounced among women with gender-specific malignancies, such as gynecologic cancers or breast cancer. Treatment, screening, and physical examinations by clinicians who are of the same gender as the sexual abuse/harassment assailant can recreate traumatic feelings.15,16
A majority of women (n = 18, 86%) in our cohort reported a history of sexual abuse or harassment and breast malignancy was the most common cancer among women. However women represent just 5.6% of the VAPHCS infusion unit treatment population. This combination of factors may explain the reasons for women veterans’ preference for privacy during treatments, access to gender-specific restrooms, and feeling more emotional support when surrounded by other women. Strategies to help patients with a history of abuse have been described and include discussions from the clinician asking about abuse history, allowing time for the patient to express fears with an examination or test, and training on how to deliver sensitive care for those with trauma.17,18
Quality Improvement
Project In the VAPHCS infusion unit, several low-cost interventions have been undertaken as a result of our survey findings. We presented our survey data to the VAPHCS Cancer Committee, accredited through the national American College of Surgeons Commission on Cancer. The committee awarded support for a yearlong QI project, including a formal framework of quarterly multidisciplinary meetings to discuss project updates, challenges, and resources. The QI project centers on education to raise awareness of survey results as well as specific interventions for improvement.
Education efforts have been applied through multiple department-wide emails, in-person education to our chemotherapy unit staff, abstract submission to national oncology conferences, and grand rounds department presentations at VAPHCS and at other VHA-affiliated university programs. Additionally, education to clinicians with specific contact information for psychology and women’s health to support mental health, trauma, and sexual abuse histories has been given to each clinician who cares for veterans in the chemotherapy unit.
We also have implemented a mandatory cancer care navigation consultation for all women veterans who have a new cancer or infusion need. The cancer care navigator has received specialized training in sensitive history-taking and provides women veterans with a direct number to reach the cancer care navigation nurse. Cancer care navigation also provides a continuum of support and referral access for psychosocial needs as indicated between infusion or health care visits. Our hope is that these resources may help offset the sentiment reflected in our cohort of women feeling unable to voice concerns to a clinician.
Other interventions underway include offering designated scheduling time each week to women so they can receive infusions in an area with other women. This may help mitigate the finding that women veterans felt more uncomfortable around other patients during infusion treatments compared with how men felt in the chemotherapy unit. We also have implemented gender-specific restrooms labeled with a sign on each bathroom door so men and women can have access to a designated restroom. Offering private or semiprivate treatment rooms is currently limited by space and capacity; however, these may offer the greatest opportunity to improve patient satisfaction, especially among women veterans. Working with the support of the VAPHCS Cancer Committee, we aim to reevaluate the impact of the education and QI efforts on gender differences and patient satisfaction at completion of the 1-year award.
Limitations
Limitations to our study include the overall small sample size. This is due to the combination of the low number of women treated at VAPHCS and many with advanced cancer who, unfortunately, have a limited overall survival and hinders accrual of a larger sample size. Other limitations included age as a possible confounder in our findings, with women representing a younger demographic compared with men. We did not collect responses on duration of infusion time, which also may impact overall satisfaction and patient experience. We also acknowledge that biologic male or female sex may not correspond to a specific individual’s gender. Use of CPRS to obtain a matched number of male and female patients through random selection relied on labeled data from the EHR. This potentially may have excluded male patients who identify as another gender that would have been captured on the anonymous survey.
Last, we restricted survey responses to online only, which excluded a small percentage who declined this approach.
Conclusions
Our findings may have broad applications to other VHA facilities and other cancer-directed treatment centers where the patient demographic and open shared infusion unit design may be similar. The study also may serve as a model of survey design and implementation from which other centers may consider improving patient satisfaction. We hope these survey results and interventions can provide insight and be used to improve patient satisfaction among all cancer patients at infusion units serving veterans and nonveterans.
Acknowledgments
We are very thankful to our cancer patients who took the time to take the survey. We also are very grateful to the VHA infusion unit nurses, staff, nurse practitioners, and physicians who have embraced this project and welcomed any changes that may positively impact treatment of veterans. Also, thank you to Tia Kohs for statistical support and Sophie West for gender discussions. Last, we specifically thank Barbara, for her pursuit of better care for women and for all veterans.
1. Clarke SA, Booth L, Velikova G, Hewison J. Social support: gender differences in cancer patients in the United Kingdom. Cancer Nurs. 2006;29(1):66-72. doi:10.1097/00002820-200601000-00012
2. Wessels H, de Graeff A, Wynia K, et al. Gender-related needs and preferences in cancer care indicate the need for an individualized approach to cancer patients. Oncologist. 2010;15(6):648-655. doi:10.1634/theoncologist.2009-0337
3. Hartigan SM, Bonnet K, Chisholm L, et al. Why do women not use the bathroom? Women’s attitudes and beliefs on using public restrooms. Int J Environ Res Public Health. 2020;17(6):2053. doi:10.3390/ijerph17062053
4. Alexander K, Walters CB, Banerjee SC. Oncology patients’ preferences regarding sexual orientation and gender identity (SOGI) disclosure and room sharing sharing. Patient Educ Couns. 2020;103(5):1041-1048. doi:10.1016/j.pec.2019.12.006
5. Centers for Disease Control and Prevention. Facts about sexual violence. Updated July 5, 2022. Accessed July 13, 2022. https://www.cdc.gov/injury/features /sexual-violence/index.html
6. US Department of Veterans Affairs. Military sexual trauma. Updated May 16, 2022. Accessed July 13, 2022. https:// www.mentalhealth.va.gov/mentalhealth/msthome/index.asp
7. Wang Z, Pukszta M. Private Rooms, Semi-open areas, or open areas for chemotherapy care: perspectives of cancer patients, families, and nursing staff. HERD. 2018;11(3):94- 108. doi:10.1177/1937586718758445
8. US Department of Veterans Affairs, National Center for Veterans Analysis and Statistics. Women veterans report: the past, present, and future of women veterans. Accessed July 13, 2022. https://www.va.gov/vetdata /docs/specialreports/women_veterans_2015_final.pdf
9. Driscoll MA, Higgins DM, Seng EK, et al. Trauma, social support, family conflict, and chronic pain in recent service veterans: does gender matter? Pain Med. 2015;16(6):1101- 1111. doi:10.1111/pme.12744
10. Fox AB, Meyer EC, Vogt D. Attitudes about the VA healthcare setting, mental illness, and mental health treatment and their relationship with VA mental health service use among female and male OEF/OIF veterans. Psychol Serv. 2015;12(1):49-58. doi:10.1037/a0038269
11. Virani SS, Woodard LD, Ramsey DJ, et al. Gender disparities in evidence-based statin therapy in patients with cardiovascular disease. Am J Cardiol. 2015;115(1):21-26. doi:10.1016/j.amjcard.2014.09.041
12. Tseng J. Sex, gender, and why the differences matter. Virtual Mentor. 2008;10(7):427-428. doi:10.1001/virtualmentor.2008.10.7.fred1-0807
13. Booij JC, Zegers M, Evers PMPJ, Hendricks M, Delnoij DMJ, Rademakers JJDJM. Improving cancer patient care: development of a generic cancer consumer quality index questionnaire for cancer patients. BMC Cancer. 2013;13(203). doi:10.1186/1471-2407-13-203
14. Meropol NJ, Egleston BL, Buzaglo JS, et al. Cancer patient preferences for quality and length of life. Cancer. 2008;113(12):3459-3466. doi:10.1002/cncr.23968 1
5. Schnur JB, Dillon MJ, Goldsmith RE, Montgomery GH. Cancer treatment experiences among survivors of childhood sexual abuse: a qualitative investigation of triggers and reactions to cumulative trauma. Palliat Support Care. 2018;16(6):767-776. doi:10.1017/S147895151700075X
16. Cadman L, Waller J, Ashdown-Barr L, Szarewski A. Barriers to cervical screening in women who have experienced sexual abuse: an exploratory study. J Fam Plann Reprod Health Care. 2012;38(4):214-220. doi:10.1136/jfprhc-2012-100378
17. Kelly S. The effects of childhood sexual abuse on women’s lives and their attitudes to cervical screening. J Fam Plann Reprod Health Care. 2012;38(4):212-213. doi:10.1136/jfprhc-2012-100418
18. McCloskey LA, Lichter E, Williams C, Gerber M, Wittenberg E, Ganz M. Assessing intimate partner violence in health care settings leads to women’s receipt of interventions and improved health. Public Health Rep. 2006;121(4):435-444. doi:10.1177/003335490612100412
1. Clarke SA, Booth L, Velikova G, Hewison J. Social support: gender differences in cancer patients in the United Kingdom. Cancer Nurs. 2006;29(1):66-72. doi:10.1097/00002820-200601000-00012
2. Wessels H, de Graeff A, Wynia K, et al. Gender-related needs and preferences in cancer care indicate the need for an individualized approach to cancer patients. Oncologist. 2010;15(6):648-655. doi:10.1634/theoncologist.2009-0337
3. Hartigan SM, Bonnet K, Chisholm L, et al. Why do women not use the bathroom? Women’s attitudes and beliefs on using public restrooms. Int J Environ Res Public Health. 2020;17(6):2053. doi:10.3390/ijerph17062053
4. Alexander K, Walters CB, Banerjee SC. Oncology patients’ preferences regarding sexual orientation and gender identity (SOGI) disclosure and room sharing sharing. Patient Educ Couns. 2020;103(5):1041-1048. doi:10.1016/j.pec.2019.12.006
5. Centers for Disease Control and Prevention. Facts about sexual violence. Updated July 5, 2022. Accessed July 13, 2022. https://www.cdc.gov/injury/features /sexual-violence/index.html
6. US Department of Veterans Affairs. Military sexual trauma. Updated May 16, 2022. Accessed July 13, 2022. https:// www.mentalhealth.va.gov/mentalhealth/msthome/index.asp
7. Wang Z, Pukszta M. Private Rooms, Semi-open areas, or open areas for chemotherapy care: perspectives of cancer patients, families, and nursing staff. HERD. 2018;11(3):94- 108. doi:10.1177/1937586718758445
8. US Department of Veterans Affairs, National Center for Veterans Analysis and Statistics. Women veterans report: the past, present, and future of women veterans. Accessed July 13, 2022. https://www.va.gov/vetdata /docs/specialreports/women_veterans_2015_final.pdf
9. Driscoll MA, Higgins DM, Seng EK, et al. Trauma, social support, family conflict, and chronic pain in recent service veterans: does gender matter? Pain Med. 2015;16(6):1101- 1111. doi:10.1111/pme.12744
10. Fox AB, Meyer EC, Vogt D. Attitudes about the VA healthcare setting, mental illness, and mental health treatment and their relationship with VA mental health service use among female and male OEF/OIF veterans. Psychol Serv. 2015;12(1):49-58. doi:10.1037/a0038269
11. Virani SS, Woodard LD, Ramsey DJ, et al. Gender disparities in evidence-based statin therapy in patients with cardiovascular disease. Am J Cardiol. 2015;115(1):21-26. doi:10.1016/j.amjcard.2014.09.041
12. Tseng J. Sex, gender, and why the differences matter. Virtual Mentor. 2008;10(7):427-428. doi:10.1001/virtualmentor.2008.10.7.fred1-0807
13. Booij JC, Zegers M, Evers PMPJ, Hendricks M, Delnoij DMJ, Rademakers JJDJM. Improving cancer patient care: development of a generic cancer consumer quality index questionnaire for cancer patients. BMC Cancer. 2013;13(203). doi:10.1186/1471-2407-13-203
14. Meropol NJ, Egleston BL, Buzaglo JS, et al. Cancer patient preferences for quality and length of life. Cancer. 2008;113(12):3459-3466. doi:10.1002/cncr.23968 1
5. Schnur JB, Dillon MJ, Goldsmith RE, Montgomery GH. Cancer treatment experiences among survivors of childhood sexual abuse: a qualitative investigation of triggers and reactions to cumulative trauma. Palliat Support Care. 2018;16(6):767-776. doi:10.1017/S147895151700075X
16. Cadman L, Waller J, Ashdown-Barr L, Szarewski A. Barriers to cervical screening in women who have experienced sexual abuse: an exploratory study. J Fam Plann Reprod Health Care. 2012;38(4):214-220. doi:10.1136/jfprhc-2012-100378
17. Kelly S. The effects of childhood sexual abuse on women’s lives and their attitudes to cervical screening. J Fam Plann Reprod Health Care. 2012;38(4):212-213. doi:10.1136/jfprhc-2012-100418
18. McCloskey LA, Lichter E, Williams C, Gerber M, Wittenberg E, Ganz M. Assessing intimate partner violence in health care settings leads to women’s receipt of interventions and improved health. Public Health Rep. 2006;121(4):435-444. doi:10.1177/003335490612100412
After cancer, abortion experience highlights post-Roe reality
The drive from Texas to the clinic in Albuquerque, N.M., took 10 hours. It was mid-April of this year. There wasn’t much to see along the mostly barren stretch, and there wasn’t much for Kailee DeSpain to do aside from think about where she was going and why.
Her husband was driving. She sensed his nervous glances toward the passenger seat where she sat struggling to quiet her thoughts.
No, she wasn’t having any pain, she told him. No, she wasn’t feeling like she did the last time or the two times before that.
This pregnancy was different. It was the first in which she feared for her own life. Her fetus – Finley – had triploidy, a rare chromosomal abnormality. Because of the condition, which affects 1%-3% of pregnancies, his heart, brain, and kidneys were not developing properly.
At 19 weeks, Finley was already struggling to draw breath from lungs squeezed inside an overcrowded chest cavity. Ms. DeSpain wanted nothing more than to carry Finley to term, hold him, meet him even for a moment before saying goodbye.
But his condition meant he would likely suffocate in utero well before that. And Ms. DeSpain knew that carrying him longer would likely raise her risk of bleeding and of her blood pressure increasing to dangerous highs.
“This could kill you,” her husband told her. “Do you realize you could die bringing a baby into this world who is not going to live? I don’t want to lose you.’”
Unlike her other pregnancies, the timing of this one and the decision she faced to end it put her health in even greater danger.
Imminent danger
On Sept. 1, 2021, a bill went into effect in Texas that banned abortions from as early as 6 weeks’ gestation. Texas Senate Bill 8 (SB8) became one of the most restrictive abortion laws in the country. It prohibited abortions whenever a fetal heartbeat, defined by lawmakers, could be detected on an ultrasound, often before many women knew they were pregnant.
The Texas abortion law was hardly the last word on the topic. Ms. DeSpain didn’t know it on her drive to New Mexico in April, but the U.S. Supreme Court was weeks away from overturning the landmark Roe v. Wade decision.
On June 24, the Supreme Court delivered its 6-3 ruling overturning Roe v. Wade, the 1973 case that granted women the right to abortion.
This decision set in motion “trigger laws” in some states – laws that essentially fully banned abortions. Those states included Ms. DeSpain’s home state of Texas, where abortion is now a felony except when the life of the mother is in peril.
However, legal definitions of what qualifies as “life-threatening” remain murky.
The law is unclear, says Lisa Harris, MD, PhD, professor in the department of obstetrics and gynecology at the University of Michigan, Ann Arbor. “What does the risk of death have to be, and how imminent must it be?” she asked in a recent editorial in the New England Journal of Medicine. Is 25% enough? 50%? Or does a woman have to be moments from dying?
“This whole thing makes me so angry,” says Shikha Jain, MD, a medical oncologist at University of Illinois Health, Chicago. “A patient may not be experiencing an emergency right now, but if we don’t take care of the situation, it may become an emergency in 2 hours or 2 days.”
Even before the Roe v. Wade decision, pregnancy had been a high-stakes endeavor for many women. In 2019, more than 750 women died from pregnancy-related events in the United States. In 2020, that number rose to 850. Each year dozens more suffer pregnancy-related events that require lifesaving interventions.
Now, in a post-Roe world, the number of maternal deaths will likely climb as more abortion bans take effect and fewer women have access to lifesaving care, experts say. A 2021 study that compared 2017 maternal mortality rates in states with different levels of abortion restrictions found that the rate of maternal mortality was almost two times higher in states that restricted abortion access compared with those that protected it – 28.5 per 100,000 women vs. 15.7.
Some women living in states with abortion bans won’t have the resources to cross state lines for care.
“This is just going to widen the health care disparities that are already so prevalent in this country,” Dr. Jain says.
Navigating a crossroads
Ms. DeSpain’s medical history reads like a checklist of pregnancy-related perils: chronic high blood pressure, persistent clotting problems, and a high risk of hemorrhage. She was also diagnosed with cervical cancer in 2020, which left her body more fragile.
Cardiovascular conditions, including hypertension and hemorrhage, are the leading causes of maternal mortality, responsible for more than one-third of pregnancy-related deaths. Preeclampsia, characterized by high blood pressure, accounts for more than 7% of maternal deaths in the United States. Although less common, genetic disorders, such as spinal muscular atrophy and triploidy, or cancer during pregnancy can put a mother and fetus at risk.
Cancer – which affects about 1 in 1,000 pregnant women and results in termination in as many as 28% of cases – brings sharp focus to the new dangers and complex decision-making patients and their doctors face as abortion bans take hold.
Before the Supreme Court decision, a pregnant woman with cancer was already facing great uncertainty. The decision to treat cancer during pregnancy involves “weighing the risk of exposing the fetus to medication vs. the risk to the mother’s untreated illness if you don’t expose the fetus to medication,” Elyce Cardonick, MD, an obstetrician at Cooper University Health Care, Camden, N.J., who specializes in high-risk pregnancies, told the National Cancer Institute.
Oncologists generally agree that it’s safe for pregnant women to receive chemotherapy during the second and third trimesters. But for women with aggressive cancers that are diagnosed in the first trimester, chemotherapy is dangerous. For women who need immunotherapy, the risks of treatment remain unclear.
In these cases, Alice S. Mims, MD, must broach the possibility of terminating the pregnancy.
“Cancer is a very urgent condition,” says Dr. Mims, a hematology specialist at the Ohio State University Comprehensive Cancer Center, Columbus, who sees patients who are pregnant. “These women may have other children at home, and they want to do their best to fight the disease so they can be around for their family long term.”
Now the changing legal landscape on abortion will put hundreds more pregnant women with cancer in danger. In a recent viewpoint article published in JAMA Oncology, Jordyn Silverstein and Katherine Van Loon, MD, MPH, estimate that during the next year, up to 420 pregnant women living in states with restricted abortion access will face threats to their cancer care and potentially their life.
“The repercussions of overturning Roe v. Wade – and the failure of the Supreme Court to provide any guidance on exceptions related to the life and health of the mother – are potentially catastrophic for a subset of women who face a life-threating diagnosis of [pregnancy-associated cancer],” they write.
The choice Ms. DeSpain faced after her cervical cancer diagnosis was different. She was not pregnant at the time, but she was at a crossroads.
Although it was caught early, the cancer was aggressive. Her oncologist recommended that she undergo a hysterectomy – the surgery that would give her the best chance for a cancer-free future. It would also mean she could no longer become pregnant.
With a less invasive procedure, on the other hand, she could still carry a child, but she would face a much greater chance that the cancer would come back.
At 27, Ms. DeSpain was not ready to close the pregnancy door. She opted for a surgery in which part of her cervix was removed, allowing her to try for another baby.
But she faced a ticking clock in the event her cancer returned.
If you want to have a baby, “try soon,” her doctor warned.
A dead end
After her cancer surgery and a third miscarriage, Ms. DeSpain and her husband were surprised and excited when in late 2021 she again became pregnant.
The first trimester seemed blissfully uneventful. As the weeks passed, Finley’s heart started to beat.
But the 16-week ultrasound signaled a turning point. The sonographer was too quiet.
“This is really bad, isn’t it?” Ms. DeSpain asked her sonographer.
The doctors told her he wouldn’t survive. Finley had no heart chambers. His heart couldn’t pump blood properly. He was missing one kidney, and his brain was split in the back. With almost no amniotic fluid, her doctor said he would likely die in utero, crushed to death without support from the protective liquid.
She fought for him anyway. She sought specialty care, followed bed rest orders, and traveled 3 hours to Houston to enroll in a clinical trial.
But every road was a dead end.
Ultimately, testing revealed Finley had triploidy, and all lines led to one point.
“There were too many things wrong, too much wrong for them to fix,” says Ms. DeSpain, recalling the news from her doctor in Houston. “I was in shock. My husband was just sitting with his hands flat on the table, staring at nothing, shaking a little bit.”
However, Finley still had a heartbeat, making an abortion after 6 weeks a felony in Texas. Even a compassionate induction was now out of the question unless her death was imminent.
Ms. DeSpain called the abortion clinic in Albuquerque and made an appointment. She would have to wait 2 weeks because of an influx of pregnant patients coming from Texas.
She welcomed the wait … just in case she changed her mind.
“At that point I wanted to carry him as far as I could,” she says.
For those 2 weeks, Ms. DeSpain remained on bed rest. She cried all day every day. She worried that Finley was experiencing pain.
Through this process, her doctor’s support helped keep her grounded.
“She cried with us in her office and said, ‘I wish that you didn’t have to go, but I think you’re doing the right thing, doing what keeps you safest,’ “ Ms. DeSpain recalls.
Ms. DeSpain declined to share the name of her doctor out of fear that even expressing compassion for a patient’s safety could put the physician in legal jeopardy and provoke harassment.
That fear is warranted. Some doctors will be forced to choose between doing what is legal – even though the law is vague – and doing what is right for patients, says law professor Jamie Abrams, who was recently diagnosed with breast cancer.
To live in a world where there’s talk of criminalizing doctors for taking care of their patients, where there’s “this national movement to position some women to be shunned and exiled for seeking care that’s right for them, their health, and might save their life is staggering and beyond comprehension,” says Ms. Abrams, professor of law at the American University Washington College of Law.
Ms. Abrams, who was diagnosed with hormone receptor–positive invasive breast cancer the same day she read the leaked Supreme Court draft on the decision to end of Roe v. Wade, said that “overnight, I became a person who would need an abortion if I became pregnant, because my treatment would compromise a healthy birth or delay necessary cancer care.” Ms. Abrams was also told she could no longer use hormonal contraception.
Dr. Harris’s advice to clinicians is to try to do what they feel is best for patients, including referring them to centers that have legal resources and protections regarding abortions.
Dr. Mims agrees and recommends that doctors reach out to those with more resources and legal backing for support. “I would advise doctors in [states with restrictive laws] to familiarize themselves with available resources and organizations taking action to deal with questionable cases,” Dr. Mims says.
‘Baby killers work here’
Following her 10-hour drive to Albuquerque, Ms. DeSpain encountered lines of protesters at the clinic. They were holding signs that said, “Abortion is murder,” and “Baby killers work here.”
“Please don’t kill your baby – we have resources for you,” a woman screeched through a megaphone as Ms. DeSpain, nearly 20 weeks’ pregnant, stepped out of the car to enter the clinic.
“I remember turning around, looking at her and making eye contact, and yelling back, ‘My baby has triploidy – he is dying! He is going to suffocate if I carry him full term. You don’t know what you’re talking about!’ “
A nurse held her hand during the procedure.
“He said, ‘You’re doing great, you’re okay,’ “ she recalls. She knew there was a chance that Finley’s face would be crushed by contractions during labor because of the lack of amniotic fluid, but she hoped not. Ms. DeSpain longed for a photo.
There was no photo to take home the next day, but Ms. DeSpain did receive Finley’s footprints, and his heartbeat – as captured by the specialty team in Houston – lives on in a stuffed giraffe.
His ashes arrived a few weeks later.
By then, the Supreme Court draft had been leaked. Ms. DeSpain knew her predicament in Texas would soon affect women across the United States and make any future pregnancy attempt for her even more risky.
The weeks and months that followed were a blur of grief, anger, and medical testing.
But she received some good news. A second triploidy pregnancy was extremely unlikely.
Several weeks later, Ms. DeSpain got more good news.
“I had a follow-up cancer appointment, and everything was completely clear,” she says.
She remains hopeful that she will be able to give birth, but her doctor cautioned that it’s no longer safe to become pregnant in Texas.
“I need you to understand that if you get pregnant and you have complications, we can’t intervene unless the baby doesn’t have a heartbeat, even if it would save your life,” Ms. DeSpain recalls her doctor saying.
If Texas remains a dangerous place to be pregnant, Ms. DeSpain and her husband will have to move.
For now, Ms. DeSpain wants people to know her story and to continue to fight for her right to govern her body.
In a public post to Facebook, she laid bare her pregnancy journey.
“No one should have to share a story like mine to justify abortion,” she wrote. “My choice is not yours to judge, and my rights are not yours to gleefully take away.”
Ms. Abrams, Ms. DeSpain, Dr. Harris, Dr. Jain, and Dr. Mims have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The drive from Texas to the clinic in Albuquerque, N.M., took 10 hours. It was mid-April of this year. There wasn’t much to see along the mostly barren stretch, and there wasn’t much for Kailee DeSpain to do aside from think about where she was going and why.
Her husband was driving. She sensed his nervous glances toward the passenger seat where she sat struggling to quiet her thoughts.
No, she wasn’t having any pain, she told him. No, she wasn’t feeling like she did the last time or the two times before that.
This pregnancy was different. It was the first in which she feared for her own life. Her fetus – Finley – had triploidy, a rare chromosomal abnormality. Because of the condition, which affects 1%-3% of pregnancies, his heart, brain, and kidneys were not developing properly.
At 19 weeks, Finley was already struggling to draw breath from lungs squeezed inside an overcrowded chest cavity. Ms. DeSpain wanted nothing more than to carry Finley to term, hold him, meet him even for a moment before saying goodbye.
But his condition meant he would likely suffocate in utero well before that. And Ms. DeSpain knew that carrying him longer would likely raise her risk of bleeding and of her blood pressure increasing to dangerous highs.
“This could kill you,” her husband told her. “Do you realize you could die bringing a baby into this world who is not going to live? I don’t want to lose you.’”
Unlike her other pregnancies, the timing of this one and the decision she faced to end it put her health in even greater danger.
Imminent danger
On Sept. 1, 2021, a bill went into effect in Texas that banned abortions from as early as 6 weeks’ gestation. Texas Senate Bill 8 (SB8) became one of the most restrictive abortion laws in the country. It prohibited abortions whenever a fetal heartbeat, defined by lawmakers, could be detected on an ultrasound, often before many women knew they were pregnant.
The Texas abortion law was hardly the last word on the topic. Ms. DeSpain didn’t know it on her drive to New Mexico in April, but the U.S. Supreme Court was weeks away from overturning the landmark Roe v. Wade decision.
On June 24, the Supreme Court delivered its 6-3 ruling overturning Roe v. Wade, the 1973 case that granted women the right to abortion.
This decision set in motion “trigger laws” in some states – laws that essentially fully banned abortions. Those states included Ms. DeSpain’s home state of Texas, where abortion is now a felony except when the life of the mother is in peril.
However, legal definitions of what qualifies as “life-threatening” remain murky.
The law is unclear, says Lisa Harris, MD, PhD, professor in the department of obstetrics and gynecology at the University of Michigan, Ann Arbor. “What does the risk of death have to be, and how imminent must it be?” she asked in a recent editorial in the New England Journal of Medicine. Is 25% enough? 50%? Or does a woman have to be moments from dying?
“This whole thing makes me so angry,” says Shikha Jain, MD, a medical oncologist at University of Illinois Health, Chicago. “A patient may not be experiencing an emergency right now, but if we don’t take care of the situation, it may become an emergency in 2 hours or 2 days.”
Even before the Roe v. Wade decision, pregnancy had been a high-stakes endeavor for many women. In 2019, more than 750 women died from pregnancy-related events in the United States. In 2020, that number rose to 850. Each year dozens more suffer pregnancy-related events that require lifesaving interventions.
Now, in a post-Roe world, the number of maternal deaths will likely climb as more abortion bans take effect and fewer women have access to lifesaving care, experts say. A 2021 study that compared 2017 maternal mortality rates in states with different levels of abortion restrictions found that the rate of maternal mortality was almost two times higher in states that restricted abortion access compared with those that protected it – 28.5 per 100,000 women vs. 15.7.
Some women living in states with abortion bans won’t have the resources to cross state lines for care.
“This is just going to widen the health care disparities that are already so prevalent in this country,” Dr. Jain says.
Navigating a crossroads
Ms. DeSpain’s medical history reads like a checklist of pregnancy-related perils: chronic high blood pressure, persistent clotting problems, and a high risk of hemorrhage. She was also diagnosed with cervical cancer in 2020, which left her body more fragile.
Cardiovascular conditions, including hypertension and hemorrhage, are the leading causes of maternal mortality, responsible for more than one-third of pregnancy-related deaths. Preeclampsia, characterized by high blood pressure, accounts for more than 7% of maternal deaths in the United States. Although less common, genetic disorders, such as spinal muscular atrophy and triploidy, or cancer during pregnancy can put a mother and fetus at risk.
Cancer – which affects about 1 in 1,000 pregnant women and results in termination in as many as 28% of cases – brings sharp focus to the new dangers and complex decision-making patients and their doctors face as abortion bans take hold.
Before the Supreme Court decision, a pregnant woman with cancer was already facing great uncertainty. The decision to treat cancer during pregnancy involves “weighing the risk of exposing the fetus to medication vs. the risk to the mother’s untreated illness if you don’t expose the fetus to medication,” Elyce Cardonick, MD, an obstetrician at Cooper University Health Care, Camden, N.J., who specializes in high-risk pregnancies, told the National Cancer Institute.
Oncologists generally agree that it’s safe for pregnant women to receive chemotherapy during the second and third trimesters. But for women with aggressive cancers that are diagnosed in the first trimester, chemotherapy is dangerous. For women who need immunotherapy, the risks of treatment remain unclear.
In these cases, Alice S. Mims, MD, must broach the possibility of terminating the pregnancy.
“Cancer is a very urgent condition,” says Dr. Mims, a hematology specialist at the Ohio State University Comprehensive Cancer Center, Columbus, who sees patients who are pregnant. “These women may have other children at home, and they want to do their best to fight the disease so they can be around for their family long term.”
Now the changing legal landscape on abortion will put hundreds more pregnant women with cancer in danger. In a recent viewpoint article published in JAMA Oncology, Jordyn Silverstein and Katherine Van Loon, MD, MPH, estimate that during the next year, up to 420 pregnant women living in states with restricted abortion access will face threats to their cancer care and potentially their life.
“The repercussions of overturning Roe v. Wade – and the failure of the Supreme Court to provide any guidance on exceptions related to the life and health of the mother – are potentially catastrophic for a subset of women who face a life-threating diagnosis of [pregnancy-associated cancer],” they write.
The choice Ms. DeSpain faced after her cervical cancer diagnosis was different. She was not pregnant at the time, but she was at a crossroads.
Although it was caught early, the cancer was aggressive. Her oncologist recommended that she undergo a hysterectomy – the surgery that would give her the best chance for a cancer-free future. It would also mean she could no longer become pregnant.
With a less invasive procedure, on the other hand, she could still carry a child, but she would face a much greater chance that the cancer would come back.
At 27, Ms. DeSpain was not ready to close the pregnancy door. She opted for a surgery in which part of her cervix was removed, allowing her to try for another baby.
But she faced a ticking clock in the event her cancer returned.
If you want to have a baby, “try soon,” her doctor warned.
A dead end
After her cancer surgery and a third miscarriage, Ms. DeSpain and her husband were surprised and excited when in late 2021 she again became pregnant.
The first trimester seemed blissfully uneventful. As the weeks passed, Finley’s heart started to beat.
But the 16-week ultrasound signaled a turning point. The sonographer was too quiet.
“This is really bad, isn’t it?” Ms. DeSpain asked her sonographer.
The doctors told her he wouldn’t survive. Finley had no heart chambers. His heart couldn’t pump blood properly. He was missing one kidney, and his brain was split in the back. With almost no amniotic fluid, her doctor said he would likely die in utero, crushed to death without support from the protective liquid.
She fought for him anyway. She sought specialty care, followed bed rest orders, and traveled 3 hours to Houston to enroll in a clinical trial.
But every road was a dead end.
Ultimately, testing revealed Finley had triploidy, and all lines led to one point.
“There were too many things wrong, too much wrong for them to fix,” says Ms. DeSpain, recalling the news from her doctor in Houston. “I was in shock. My husband was just sitting with his hands flat on the table, staring at nothing, shaking a little bit.”
However, Finley still had a heartbeat, making an abortion after 6 weeks a felony in Texas. Even a compassionate induction was now out of the question unless her death was imminent.
Ms. DeSpain called the abortion clinic in Albuquerque and made an appointment. She would have to wait 2 weeks because of an influx of pregnant patients coming from Texas.
She welcomed the wait … just in case she changed her mind.
“At that point I wanted to carry him as far as I could,” she says.
For those 2 weeks, Ms. DeSpain remained on bed rest. She cried all day every day. She worried that Finley was experiencing pain.
Through this process, her doctor’s support helped keep her grounded.
“She cried with us in her office and said, ‘I wish that you didn’t have to go, but I think you’re doing the right thing, doing what keeps you safest,’ “ Ms. DeSpain recalls.
Ms. DeSpain declined to share the name of her doctor out of fear that even expressing compassion for a patient’s safety could put the physician in legal jeopardy and provoke harassment.
That fear is warranted. Some doctors will be forced to choose between doing what is legal – even though the law is vague – and doing what is right for patients, says law professor Jamie Abrams, who was recently diagnosed with breast cancer.
To live in a world where there’s talk of criminalizing doctors for taking care of their patients, where there’s “this national movement to position some women to be shunned and exiled for seeking care that’s right for them, their health, and might save their life is staggering and beyond comprehension,” says Ms. Abrams, professor of law at the American University Washington College of Law.
Ms. Abrams, who was diagnosed with hormone receptor–positive invasive breast cancer the same day she read the leaked Supreme Court draft on the decision to end of Roe v. Wade, said that “overnight, I became a person who would need an abortion if I became pregnant, because my treatment would compromise a healthy birth or delay necessary cancer care.” Ms. Abrams was also told she could no longer use hormonal contraception.
Dr. Harris’s advice to clinicians is to try to do what they feel is best for patients, including referring them to centers that have legal resources and protections regarding abortions.
Dr. Mims agrees and recommends that doctors reach out to those with more resources and legal backing for support. “I would advise doctors in [states with restrictive laws] to familiarize themselves with available resources and organizations taking action to deal with questionable cases,” Dr. Mims says.
‘Baby killers work here’
Following her 10-hour drive to Albuquerque, Ms. DeSpain encountered lines of protesters at the clinic. They were holding signs that said, “Abortion is murder,” and “Baby killers work here.”
“Please don’t kill your baby – we have resources for you,” a woman screeched through a megaphone as Ms. DeSpain, nearly 20 weeks’ pregnant, stepped out of the car to enter the clinic.
“I remember turning around, looking at her and making eye contact, and yelling back, ‘My baby has triploidy – he is dying! He is going to suffocate if I carry him full term. You don’t know what you’re talking about!’ “
A nurse held her hand during the procedure.
“He said, ‘You’re doing great, you’re okay,’ “ she recalls. She knew there was a chance that Finley’s face would be crushed by contractions during labor because of the lack of amniotic fluid, but she hoped not. Ms. DeSpain longed for a photo.
There was no photo to take home the next day, but Ms. DeSpain did receive Finley’s footprints, and his heartbeat – as captured by the specialty team in Houston – lives on in a stuffed giraffe.
His ashes arrived a few weeks later.
By then, the Supreme Court draft had been leaked. Ms. DeSpain knew her predicament in Texas would soon affect women across the United States and make any future pregnancy attempt for her even more risky.
The weeks and months that followed were a blur of grief, anger, and medical testing.
But she received some good news. A second triploidy pregnancy was extremely unlikely.
Several weeks later, Ms. DeSpain got more good news.
“I had a follow-up cancer appointment, and everything was completely clear,” she says.
She remains hopeful that she will be able to give birth, but her doctor cautioned that it’s no longer safe to become pregnant in Texas.
“I need you to understand that if you get pregnant and you have complications, we can’t intervene unless the baby doesn’t have a heartbeat, even if it would save your life,” Ms. DeSpain recalls her doctor saying.
If Texas remains a dangerous place to be pregnant, Ms. DeSpain and her husband will have to move.
For now, Ms. DeSpain wants people to know her story and to continue to fight for her right to govern her body.
In a public post to Facebook, she laid bare her pregnancy journey.
“No one should have to share a story like mine to justify abortion,” she wrote. “My choice is not yours to judge, and my rights are not yours to gleefully take away.”
Ms. Abrams, Ms. DeSpain, Dr. Harris, Dr. Jain, and Dr. Mims have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The drive from Texas to the clinic in Albuquerque, N.M., took 10 hours. It was mid-April of this year. There wasn’t much to see along the mostly barren stretch, and there wasn’t much for Kailee DeSpain to do aside from think about where she was going and why.
Her husband was driving. She sensed his nervous glances toward the passenger seat where she sat struggling to quiet her thoughts.
No, she wasn’t having any pain, she told him. No, she wasn’t feeling like she did the last time or the two times before that.
This pregnancy was different. It was the first in which she feared for her own life. Her fetus – Finley – had triploidy, a rare chromosomal abnormality. Because of the condition, which affects 1%-3% of pregnancies, his heart, brain, and kidneys were not developing properly.
At 19 weeks, Finley was already struggling to draw breath from lungs squeezed inside an overcrowded chest cavity. Ms. DeSpain wanted nothing more than to carry Finley to term, hold him, meet him even for a moment before saying goodbye.
But his condition meant he would likely suffocate in utero well before that. And Ms. DeSpain knew that carrying him longer would likely raise her risk of bleeding and of her blood pressure increasing to dangerous highs.
“This could kill you,” her husband told her. “Do you realize you could die bringing a baby into this world who is not going to live? I don’t want to lose you.’”
Unlike her other pregnancies, the timing of this one and the decision she faced to end it put her health in even greater danger.
Imminent danger
On Sept. 1, 2021, a bill went into effect in Texas that banned abortions from as early as 6 weeks’ gestation. Texas Senate Bill 8 (SB8) became one of the most restrictive abortion laws in the country. It prohibited abortions whenever a fetal heartbeat, defined by lawmakers, could be detected on an ultrasound, often before many women knew they were pregnant.
The Texas abortion law was hardly the last word on the topic. Ms. DeSpain didn’t know it on her drive to New Mexico in April, but the U.S. Supreme Court was weeks away from overturning the landmark Roe v. Wade decision.
On June 24, the Supreme Court delivered its 6-3 ruling overturning Roe v. Wade, the 1973 case that granted women the right to abortion.
This decision set in motion “trigger laws” in some states – laws that essentially fully banned abortions. Those states included Ms. DeSpain’s home state of Texas, where abortion is now a felony except when the life of the mother is in peril.
However, legal definitions of what qualifies as “life-threatening” remain murky.
The law is unclear, says Lisa Harris, MD, PhD, professor in the department of obstetrics and gynecology at the University of Michigan, Ann Arbor. “What does the risk of death have to be, and how imminent must it be?” she asked in a recent editorial in the New England Journal of Medicine. Is 25% enough? 50%? Or does a woman have to be moments from dying?
“This whole thing makes me so angry,” says Shikha Jain, MD, a medical oncologist at University of Illinois Health, Chicago. “A patient may not be experiencing an emergency right now, but if we don’t take care of the situation, it may become an emergency in 2 hours or 2 days.”
Even before the Roe v. Wade decision, pregnancy had been a high-stakes endeavor for many women. In 2019, more than 750 women died from pregnancy-related events in the United States. In 2020, that number rose to 850. Each year dozens more suffer pregnancy-related events that require lifesaving interventions.
Now, in a post-Roe world, the number of maternal deaths will likely climb as more abortion bans take effect and fewer women have access to lifesaving care, experts say. A 2021 study that compared 2017 maternal mortality rates in states with different levels of abortion restrictions found that the rate of maternal mortality was almost two times higher in states that restricted abortion access compared with those that protected it – 28.5 per 100,000 women vs. 15.7.
Some women living in states with abortion bans won’t have the resources to cross state lines for care.
“This is just going to widen the health care disparities that are already so prevalent in this country,” Dr. Jain says.
Navigating a crossroads
Ms. DeSpain’s medical history reads like a checklist of pregnancy-related perils: chronic high blood pressure, persistent clotting problems, and a high risk of hemorrhage. She was also diagnosed with cervical cancer in 2020, which left her body more fragile.
Cardiovascular conditions, including hypertension and hemorrhage, are the leading causes of maternal mortality, responsible for more than one-third of pregnancy-related deaths. Preeclampsia, characterized by high blood pressure, accounts for more than 7% of maternal deaths in the United States. Although less common, genetic disorders, such as spinal muscular atrophy and triploidy, or cancer during pregnancy can put a mother and fetus at risk.
Cancer – which affects about 1 in 1,000 pregnant women and results in termination in as many as 28% of cases – brings sharp focus to the new dangers and complex decision-making patients and their doctors face as abortion bans take hold.
Before the Supreme Court decision, a pregnant woman with cancer was already facing great uncertainty. The decision to treat cancer during pregnancy involves “weighing the risk of exposing the fetus to medication vs. the risk to the mother’s untreated illness if you don’t expose the fetus to medication,” Elyce Cardonick, MD, an obstetrician at Cooper University Health Care, Camden, N.J., who specializes in high-risk pregnancies, told the National Cancer Institute.
Oncologists generally agree that it’s safe for pregnant women to receive chemotherapy during the second and third trimesters. But for women with aggressive cancers that are diagnosed in the first trimester, chemotherapy is dangerous. For women who need immunotherapy, the risks of treatment remain unclear.
In these cases, Alice S. Mims, MD, must broach the possibility of terminating the pregnancy.
“Cancer is a very urgent condition,” says Dr. Mims, a hematology specialist at the Ohio State University Comprehensive Cancer Center, Columbus, who sees patients who are pregnant. “These women may have other children at home, and they want to do their best to fight the disease so they can be around for their family long term.”
Now the changing legal landscape on abortion will put hundreds more pregnant women with cancer in danger. In a recent viewpoint article published in JAMA Oncology, Jordyn Silverstein and Katherine Van Loon, MD, MPH, estimate that during the next year, up to 420 pregnant women living in states with restricted abortion access will face threats to their cancer care and potentially their life.
“The repercussions of overturning Roe v. Wade – and the failure of the Supreme Court to provide any guidance on exceptions related to the life and health of the mother – are potentially catastrophic for a subset of women who face a life-threating diagnosis of [pregnancy-associated cancer],” they write.
The choice Ms. DeSpain faced after her cervical cancer diagnosis was different. She was not pregnant at the time, but she was at a crossroads.
Although it was caught early, the cancer was aggressive. Her oncologist recommended that she undergo a hysterectomy – the surgery that would give her the best chance for a cancer-free future. It would also mean she could no longer become pregnant.
With a less invasive procedure, on the other hand, she could still carry a child, but she would face a much greater chance that the cancer would come back.
At 27, Ms. DeSpain was not ready to close the pregnancy door. She opted for a surgery in which part of her cervix was removed, allowing her to try for another baby.
But she faced a ticking clock in the event her cancer returned.
If you want to have a baby, “try soon,” her doctor warned.
A dead end
After her cancer surgery and a third miscarriage, Ms. DeSpain and her husband were surprised and excited when in late 2021 she again became pregnant.
The first trimester seemed blissfully uneventful. As the weeks passed, Finley’s heart started to beat.
But the 16-week ultrasound signaled a turning point. The sonographer was too quiet.
“This is really bad, isn’t it?” Ms. DeSpain asked her sonographer.
The doctors told her he wouldn’t survive. Finley had no heart chambers. His heart couldn’t pump blood properly. He was missing one kidney, and his brain was split in the back. With almost no amniotic fluid, her doctor said he would likely die in utero, crushed to death without support from the protective liquid.
She fought for him anyway. She sought specialty care, followed bed rest orders, and traveled 3 hours to Houston to enroll in a clinical trial.
But every road was a dead end.
Ultimately, testing revealed Finley had triploidy, and all lines led to one point.
“There were too many things wrong, too much wrong for them to fix,” says Ms. DeSpain, recalling the news from her doctor in Houston. “I was in shock. My husband was just sitting with his hands flat on the table, staring at nothing, shaking a little bit.”
However, Finley still had a heartbeat, making an abortion after 6 weeks a felony in Texas. Even a compassionate induction was now out of the question unless her death was imminent.
Ms. DeSpain called the abortion clinic in Albuquerque and made an appointment. She would have to wait 2 weeks because of an influx of pregnant patients coming from Texas.
She welcomed the wait … just in case she changed her mind.
“At that point I wanted to carry him as far as I could,” she says.
For those 2 weeks, Ms. DeSpain remained on bed rest. She cried all day every day. She worried that Finley was experiencing pain.
Through this process, her doctor’s support helped keep her grounded.
“She cried with us in her office and said, ‘I wish that you didn’t have to go, but I think you’re doing the right thing, doing what keeps you safest,’ “ Ms. DeSpain recalls.
Ms. DeSpain declined to share the name of her doctor out of fear that even expressing compassion for a patient’s safety could put the physician in legal jeopardy and provoke harassment.
That fear is warranted. Some doctors will be forced to choose between doing what is legal – even though the law is vague – and doing what is right for patients, says law professor Jamie Abrams, who was recently diagnosed with breast cancer.
To live in a world where there’s talk of criminalizing doctors for taking care of their patients, where there’s “this national movement to position some women to be shunned and exiled for seeking care that’s right for them, their health, and might save their life is staggering and beyond comprehension,” says Ms. Abrams, professor of law at the American University Washington College of Law.
Ms. Abrams, who was diagnosed with hormone receptor–positive invasive breast cancer the same day she read the leaked Supreme Court draft on the decision to end of Roe v. Wade, said that “overnight, I became a person who would need an abortion if I became pregnant, because my treatment would compromise a healthy birth or delay necessary cancer care.” Ms. Abrams was also told she could no longer use hormonal contraception.
Dr. Harris’s advice to clinicians is to try to do what they feel is best for patients, including referring them to centers that have legal resources and protections regarding abortions.
Dr. Mims agrees and recommends that doctors reach out to those with more resources and legal backing for support. “I would advise doctors in [states with restrictive laws] to familiarize themselves with available resources and organizations taking action to deal with questionable cases,” Dr. Mims says.
‘Baby killers work here’
Following her 10-hour drive to Albuquerque, Ms. DeSpain encountered lines of protesters at the clinic. They were holding signs that said, “Abortion is murder,” and “Baby killers work here.”
“Please don’t kill your baby – we have resources for you,” a woman screeched through a megaphone as Ms. DeSpain, nearly 20 weeks’ pregnant, stepped out of the car to enter the clinic.
“I remember turning around, looking at her and making eye contact, and yelling back, ‘My baby has triploidy – he is dying! He is going to suffocate if I carry him full term. You don’t know what you’re talking about!’ “
A nurse held her hand during the procedure.
“He said, ‘You’re doing great, you’re okay,’ “ she recalls. She knew there was a chance that Finley’s face would be crushed by contractions during labor because of the lack of amniotic fluid, but she hoped not. Ms. DeSpain longed for a photo.
There was no photo to take home the next day, but Ms. DeSpain did receive Finley’s footprints, and his heartbeat – as captured by the specialty team in Houston – lives on in a stuffed giraffe.
His ashes arrived a few weeks later.
By then, the Supreme Court draft had been leaked. Ms. DeSpain knew her predicament in Texas would soon affect women across the United States and make any future pregnancy attempt for her even more risky.
The weeks and months that followed were a blur of grief, anger, and medical testing.
But she received some good news. A second triploidy pregnancy was extremely unlikely.
Several weeks later, Ms. DeSpain got more good news.
“I had a follow-up cancer appointment, and everything was completely clear,” she says.
She remains hopeful that she will be able to give birth, but her doctor cautioned that it’s no longer safe to become pregnant in Texas.
“I need you to understand that if you get pregnant and you have complications, we can’t intervene unless the baby doesn’t have a heartbeat, even if it would save your life,” Ms. DeSpain recalls her doctor saying.
If Texas remains a dangerous place to be pregnant, Ms. DeSpain and her husband will have to move.
For now, Ms. DeSpain wants people to know her story and to continue to fight for her right to govern her body.
In a public post to Facebook, she laid bare her pregnancy journey.
“No one should have to share a story like mine to justify abortion,” she wrote. “My choice is not yours to judge, and my rights are not yours to gleefully take away.”
Ms. Abrams, Ms. DeSpain, Dr. Harris, Dr. Jain, and Dr. Mims have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Incomplete recovery common 6 months after mild TBI
, new data from the TRACK-TBI study shows.
“Seeing that more than half of the GCS [Glasgow Coma Score] 15, CT-negative TBI cohort in our study were not back to their preinjury baseline at 6 months was surprising and impacts the millions of Americans who suffer from concussions annually,” said lead author Debbie Madhok, MD, with department of emergency medicine, University of California, San Francisco.
“These results highlight the importance of improving care pathways for concussion, particularly from the emergency department,” Dr. Madhok said.
The findings were published online in JAMA Network Open.
The short- and long-term outcomes in the large group of patients who come into the ED with TBI, a GCS of 15, and without acute intracranial traumatic injury (defined as a negative head CT scan) remain poorly understood, the investigators noted. To investigate further, they evaluated outcomes at 2 weeks and 6 months in 991 of these patients (mean age, 38 years; 64% men) from the TRACK-TBI study.
Among the 751 (76%) participants followed up at 2 weeks after the injury, only 204 (27%) had functional recovery – with a Glasgow Outcome Scale-Extended (GOS-E) score of 8. The remaining 547 (73%) had incomplete recovery (GOS-E scores < 8).
Among the 659 patients (66%) followed up at 6 months after the injury, 287 (44%) had functional recovery and 372 (56%) had incomplete recovery.
Most patients who failed to recover completely reported they had not returned to their preinjury life (88%). They described trouble returning to social activities outside the home and disruptions in family relationships and friendships.
The researchers noted that the study population had a high rate of preinjury psychiatric comorbidities, and these patients were more likely to have incomplete recovery than those without psychiatric comorbidities. This aligns with results from previous studies, they added.
The investigators also noted that patients with mild TBI without acute intracranial trauma are typically managed by ED personnel.
“These findings highlight the importance of ED clinicians being aware of the risk of incomplete recovery for patients with a mild TBI (that is, GCS score of 15 and negative head CT scan) and providing accurate education and timely referral information before ED discharge,” they wrote.
The study was funded by grants from the National Foundation of Emergency Medicine, the National Institute of Neurological Disorders and Stroke, and the U.S. Department of Defense Traumatic Brain Injury Endpoints Development Initiative. Dr. Madhok has reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, new data from the TRACK-TBI study shows.
“Seeing that more than half of the GCS [Glasgow Coma Score] 15, CT-negative TBI cohort in our study were not back to their preinjury baseline at 6 months was surprising and impacts the millions of Americans who suffer from concussions annually,” said lead author Debbie Madhok, MD, with department of emergency medicine, University of California, San Francisco.
“These results highlight the importance of improving care pathways for concussion, particularly from the emergency department,” Dr. Madhok said.
The findings were published online in JAMA Network Open.
The short- and long-term outcomes in the large group of patients who come into the ED with TBI, a GCS of 15, and without acute intracranial traumatic injury (defined as a negative head CT scan) remain poorly understood, the investigators noted. To investigate further, they evaluated outcomes at 2 weeks and 6 months in 991 of these patients (mean age, 38 years; 64% men) from the TRACK-TBI study.
Among the 751 (76%) participants followed up at 2 weeks after the injury, only 204 (27%) had functional recovery – with a Glasgow Outcome Scale-Extended (GOS-E) score of 8. The remaining 547 (73%) had incomplete recovery (GOS-E scores < 8).
Among the 659 patients (66%) followed up at 6 months after the injury, 287 (44%) had functional recovery and 372 (56%) had incomplete recovery.
Most patients who failed to recover completely reported they had not returned to their preinjury life (88%). They described trouble returning to social activities outside the home and disruptions in family relationships and friendships.
The researchers noted that the study population had a high rate of preinjury psychiatric comorbidities, and these patients were more likely to have incomplete recovery than those without psychiatric comorbidities. This aligns with results from previous studies, they added.
The investigators also noted that patients with mild TBI without acute intracranial trauma are typically managed by ED personnel.
“These findings highlight the importance of ED clinicians being aware of the risk of incomplete recovery for patients with a mild TBI (that is, GCS score of 15 and negative head CT scan) and providing accurate education and timely referral information before ED discharge,” they wrote.
The study was funded by grants from the National Foundation of Emergency Medicine, the National Institute of Neurological Disorders and Stroke, and the U.S. Department of Defense Traumatic Brain Injury Endpoints Development Initiative. Dr. Madhok has reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, new data from the TRACK-TBI study shows.
“Seeing that more than half of the GCS [Glasgow Coma Score] 15, CT-negative TBI cohort in our study were not back to their preinjury baseline at 6 months was surprising and impacts the millions of Americans who suffer from concussions annually,” said lead author Debbie Madhok, MD, with department of emergency medicine, University of California, San Francisco.
“These results highlight the importance of improving care pathways for concussion, particularly from the emergency department,” Dr. Madhok said.
The findings were published online in JAMA Network Open.
The short- and long-term outcomes in the large group of patients who come into the ED with TBI, a GCS of 15, and without acute intracranial traumatic injury (defined as a negative head CT scan) remain poorly understood, the investigators noted. To investigate further, they evaluated outcomes at 2 weeks and 6 months in 991 of these patients (mean age, 38 years; 64% men) from the TRACK-TBI study.
Among the 751 (76%) participants followed up at 2 weeks after the injury, only 204 (27%) had functional recovery – with a Glasgow Outcome Scale-Extended (GOS-E) score of 8. The remaining 547 (73%) had incomplete recovery (GOS-E scores < 8).
Among the 659 patients (66%) followed up at 6 months after the injury, 287 (44%) had functional recovery and 372 (56%) had incomplete recovery.
Most patients who failed to recover completely reported they had not returned to their preinjury life (88%). They described trouble returning to social activities outside the home and disruptions in family relationships and friendships.
The researchers noted that the study population had a high rate of preinjury psychiatric comorbidities, and these patients were more likely to have incomplete recovery than those without psychiatric comorbidities. This aligns with results from previous studies, they added.
The investigators also noted that patients with mild TBI without acute intracranial trauma are typically managed by ED personnel.
“These findings highlight the importance of ED clinicians being aware of the risk of incomplete recovery for patients with a mild TBI (that is, GCS score of 15 and negative head CT scan) and providing accurate education and timely referral information before ED discharge,” they wrote.
The study was funded by grants from the National Foundation of Emergency Medicine, the National Institute of Neurological Disorders and Stroke, and the U.S. Department of Defense Traumatic Brain Injury Endpoints Development Initiative. Dr. Madhok has reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM JAMA NETWORK OPEN
Leukemia rates two to three times higher in children born near fracking
Children born near fracking and other “unconventional” drilling sites are at two to three times greater risk of developing childhood leukemia, according to new research.
The study, published in the journal Environmental Health Perspectives, compared proximity of homes to unconventional oil and gas development (UOGD) sites and risk of the most common form of childhood leukemia, acute lymphoblastic leukemia (ALL).
Researchers looked at 405 children aged 2-7 diagnosed with ALL in Pennsylvania from 2009 to 2017. These children were compared to a control group of 2,080 without the disease matched on the year of birth.
“Unconventional oil and gas development can both use and release chemicals that have been linked to cancer,” study coauthor Nicole Deziel, PhD, of the Yale School of Public Health, New Haven, Conn., said in a statement . She noted that the possibility that children living in close proximity to such sites are “exposed to these chemical carcinogens is a major public health concern.”
About 17 million Americans live within a half-mile of active oil and gas production, according to the Oil & Gas Threat Map, Common Dreams reports. That number includes 4 million children.
The Yale study also found that drinking water could be an important pathway of exposure to oil- and gas-related chemicals used in the UOGD methods of extraction.
Researchers used a new metric that measures exposure to contaminated drinking water and distance to a well. They were able to identify UOGD-affected wells that fell within watersheds where children and their families likely obtained their water.
“Previous health studies have found links between proximity to oil and gas drilling and various children’s health outcomes,” said Dr. Deziel. “This study is among the few to focus on drinking water specifically and the first to apply a novel metric designed to capture potential exposure through this pathway.”
A version of this article first appeared on WebMD.com.
Children born near fracking and other “unconventional” drilling sites are at two to three times greater risk of developing childhood leukemia, according to new research.
The study, published in the journal Environmental Health Perspectives, compared proximity of homes to unconventional oil and gas development (UOGD) sites and risk of the most common form of childhood leukemia, acute lymphoblastic leukemia (ALL).
Researchers looked at 405 children aged 2-7 diagnosed with ALL in Pennsylvania from 2009 to 2017. These children were compared to a control group of 2,080 without the disease matched on the year of birth.
“Unconventional oil and gas development can both use and release chemicals that have been linked to cancer,” study coauthor Nicole Deziel, PhD, of the Yale School of Public Health, New Haven, Conn., said in a statement . She noted that the possibility that children living in close proximity to such sites are “exposed to these chemical carcinogens is a major public health concern.”
About 17 million Americans live within a half-mile of active oil and gas production, according to the Oil & Gas Threat Map, Common Dreams reports. That number includes 4 million children.
The Yale study also found that drinking water could be an important pathway of exposure to oil- and gas-related chemicals used in the UOGD methods of extraction.
Researchers used a new metric that measures exposure to contaminated drinking water and distance to a well. They were able to identify UOGD-affected wells that fell within watersheds where children and their families likely obtained their water.
“Previous health studies have found links between proximity to oil and gas drilling and various children’s health outcomes,” said Dr. Deziel. “This study is among the few to focus on drinking water specifically and the first to apply a novel metric designed to capture potential exposure through this pathway.”
A version of this article first appeared on WebMD.com.
Children born near fracking and other “unconventional” drilling sites are at two to three times greater risk of developing childhood leukemia, according to new research.
The study, published in the journal Environmental Health Perspectives, compared proximity of homes to unconventional oil and gas development (UOGD) sites and risk of the most common form of childhood leukemia, acute lymphoblastic leukemia (ALL).
Researchers looked at 405 children aged 2-7 diagnosed with ALL in Pennsylvania from 2009 to 2017. These children were compared to a control group of 2,080 without the disease matched on the year of birth.
“Unconventional oil and gas development can both use and release chemicals that have been linked to cancer,” study coauthor Nicole Deziel, PhD, of the Yale School of Public Health, New Haven, Conn., said in a statement . She noted that the possibility that children living in close proximity to such sites are “exposed to these chemical carcinogens is a major public health concern.”
About 17 million Americans live within a half-mile of active oil and gas production, according to the Oil & Gas Threat Map, Common Dreams reports. That number includes 4 million children.
The Yale study also found that drinking water could be an important pathway of exposure to oil- and gas-related chemicals used in the UOGD methods of extraction.
Researchers used a new metric that measures exposure to contaminated drinking water and distance to a well. They were able to identify UOGD-affected wells that fell within watersheds where children and their families likely obtained their water.
“Previous health studies have found links between proximity to oil and gas drilling and various children’s health outcomes,” said Dr. Deziel. “This study is among the few to focus on drinking water specifically and the first to apply a novel metric designed to capture potential exposure through this pathway.”
A version of this article first appeared on WebMD.com.
Are artificial sweeteners really harmless?
New research discounts the long-held notion that aspartame and other nonnutritive sweeteners (NNS) have no effect on the human body.
Researchers found that these sugar substitutes are not metabolically inert and can alter the gut microbiome in a way that can influence blood glucose levels.
The study was published online in the journal Cell.
Gut reaction?
Several years ago, a team led by Eran Elinav, MD, PhD, an immunologist and microbiome researcher at the Weizmann Institute of Science, Rehovot, Israel, observed that these sweeteners affect the microbiome of mice in ways that could affect glycemic responses.
They have now confirmed this observation in a randomized controlled trial with 120 healthy adults.
Each sweetener “significantly and distinctly” altered stool and oral microbiome, and two of them (saccharin and sucralose) significantly impaired glucose tolerance, the researchers reported.
“Importantly, by performing extensive fecal transplantation of human microbiomes into germ-free mice, we demonstrate a causal and individualized link between NNS-altered microbiomes and glucose intolerance developing in non–NNS-consuming recipient mice,” they said.
They noted that the effects of these sweeteners will likely vary from person to person because of the unique composition of an individual’s microbiome.
“We need to raise awareness of the fact that NNS are not inert to the human body as we originally believed. With that said, the clinical health implications of the changes they may elicit in humans remain unknown and merit future long-term studies,” Dr. Elinav said in a news release.
For now, Dr. Elinav said it’s his personal view that “drinking only water seems to be the best solution.”
Weighing the evidence
Several experts weighed in on the results in a statement from the U.K. nonprofit organization, Science Media Centre.
Duane Mellor, PhD, RD, RNutr, registered dietitian and senior teaching fellow, Aston University, Birmingham, England, notes that the study does not show a link between all NNS and higher blood glucose levels in the long term (only after a glucose tolerance test).
“It did suggest, though, that some individuals who do not normally consume sweeteners may not tolerate glucose as well after consuming six sachets of either saccharin or sucralose mixed with glucose per day,” Dr. Mellor says.
Kim Barrett, PhD, distinguished professor of physiology and membrane biology, University of California, Davis, concurs, saying “this well-designed study indicates the potential for NNS to have adverse effects in at least some individuals.”
The study also does not provide any information about how people who normally consume sweeteners or people with either type 1 or type 2 diabetes respond to NNS.
“Therefore, for some people, it is likely to be a better option and more sustainable approach to use sweeteners as a ‘stepping stone’ allowing them to reduce the amount of added sugar in foods and drinks, to reduce their sugar intake and still enjoy what they eat and drink, on the way to reducing both added sugar and sweeteners in their diet,” Dr. Mellor suggests.
Kevin McConway, PhD, with the Open University, Milton Keynes, England, said it’s “important to understand that the research is not saying that these sweeteners are worse for us, in heath terms, than sugar.
“But exactly what the health consequences of all this, if any, might be is a subject for future research,” Dr. McConway added.
Kathy Redfern, PhD, lecturer in human nutrition, University of Plymouth (England) agrees.
“We still have a lot to learn about the human microbiome, and although this study suggests two of the sweeteners tested in this study (sucralose and saccharin) significantly affected glucose tolerance, these deviations were small,” she says.
The International Sweeteners Association also weighs in, saying, “No conclusions about the effects of low/no calorie sweeteners on glucose control or overall health can be extrapolated from this study for the general population or for people who typically consume sweeteners, including people living with diabetes.”
They add “a recent review of the literature concluded that there is clear evidence that changes in the diet unrelated to low/no calorie sweeteners consumption are likely the major determinants of change in gut microbiota.”
Nevertheless, Dr. Redfern says the results “warrant further investigation to assess how small changes in glucose tolerance in response to NNS consumption may influence longer-term glucose tolerance and risk for metabolic complications, such as type 2 diabetes.”
The study had no specific funding. Dr. Elinav is a scientific founder of DayTwo and BiomX, a paid consultant to Hello Inside and Aposense, and a member of the scientific advisory board of Cell. Dr. Mellor has provided consultancy to the International Sweetener Agency and has worked on projects funded by the Food Standards Agency that investigated the health effects of aspartame. Dr. Barrett, Dr. McConway, and Dr. Redfern report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
This article was updated 8/29/22.
New research discounts the long-held notion that aspartame and other nonnutritive sweeteners (NNS) have no effect on the human body.
Researchers found that these sugar substitutes are not metabolically inert and can alter the gut microbiome in a way that can influence blood glucose levels.
The study was published online in the journal Cell.
Gut reaction?
Several years ago, a team led by Eran Elinav, MD, PhD, an immunologist and microbiome researcher at the Weizmann Institute of Science, Rehovot, Israel, observed that these sweeteners affect the microbiome of mice in ways that could affect glycemic responses.
They have now confirmed this observation in a randomized controlled trial with 120 healthy adults.
Each sweetener “significantly and distinctly” altered stool and oral microbiome, and two of them (saccharin and sucralose) significantly impaired glucose tolerance, the researchers reported.
“Importantly, by performing extensive fecal transplantation of human microbiomes into germ-free mice, we demonstrate a causal and individualized link between NNS-altered microbiomes and glucose intolerance developing in non–NNS-consuming recipient mice,” they said.
They noted that the effects of these sweeteners will likely vary from person to person because of the unique composition of an individual’s microbiome.
“We need to raise awareness of the fact that NNS are not inert to the human body as we originally believed. With that said, the clinical health implications of the changes they may elicit in humans remain unknown and merit future long-term studies,” Dr. Elinav said in a news release.
For now, Dr. Elinav said it’s his personal view that “drinking only water seems to be the best solution.”
Weighing the evidence
Several experts weighed in on the results in a statement from the U.K. nonprofit organization, Science Media Centre.
Duane Mellor, PhD, RD, RNutr, registered dietitian and senior teaching fellow, Aston University, Birmingham, England, notes that the study does not show a link between all NNS and higher blood glucose levels in the long term (only after a glucose tolerance test).
“It did suggest, though, that some individuals who do not normally consume sweeteners may not tolerate glucose as well after consuming six sachets of either saccharin or sucralose mixed with glucose per day,” Dr. Mellor says.
Kim Barrett, PhD, distinguished professor of physiology and membrane biology, University of California, Davis, concurs, saying “this well-designed study indicates the potential for NNS to have adverse effects in at least some individuals.”
The study also does not provide any information about how people who normally consume sweeteners or people with either type 1 or type 2 diabetes respond to NNS.
“Therefore, for some people, it is likely to be a better option and more sustainable approach to use sweeteners as a ‘stepping stone’ allowing them to reduce the amount of added sugar in foods and drinks, to reduce their sugar intake and still enjoy what they eat and drink, on the way to reducing both added sugar and sweeteners in their diet,” Dr. Mellor suggests.
Kevin McConway, PhD, with the Open University, Milton Keynes, England, said it’s “important to understand that the research is not saying that these sweeteners are worse for us, in heath terms, than sugar.
“But exactly what the health consequences of all this, if any, might be is a subject for future research,” Dr. McConway added.
Kathy Redfern, PhD, lecturer in human nutrition, University of Plymouth (England) agrees.
“We still have a lot to learn about the human microbiome, and although this study suggests two of the sweeteners tested in this study (sucralose and saccharin) significantly affected glucose tolerance, these deviations were small,” she says.
The International Sweeteners Association also weighs in, saying, “No conclusions about the effects of low/no calorie sweeteners on glucose control or overall health can be extrapolated from this study for the general population or for people who typically consume sweeteners, including people living with diabetes.”
They add “a recent review of the literature concluded that there is clear evidence that changes in the diet unrelated to low/no calorie sweeteners consumption are likely the major determinants of change in gut microbiota.”
Nevertheless, Dr. Redfern says the results “warrant further investigation to assess how small changes in glucose tolerance in response to NNS consumption may influence longer-term glucose tolerance and risk for metabolic complications, such as type 2 diabetes.”
The study had no specific funding. Dr. Elinav is a scientific founder of DayTwo and BiomX, a paid consultant to Hello Inside and Aposense, and a member of the scientific advisory board of Cell. Dr. Mellor has provided consultancy to the International Sweetener Agency and has worked on projects funded by the Food Standards Agency that investigated the health effects of aspartame. Dr. Barrett, Dr. McConway, and Dr. Redfern report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
This article was updated 8/29/22.
New research discounts the long-held notion that aspartame and other nonnutritive sweeteners (NNS) have no effect on the human body.
Researchers found that these sugar substitutes are not metabolically inert and can alter the gut microbiome in a way that can influence blood glucose levels.
The study was published online in the journal Cell.
Gut reaction?
Several years ago, a team led by Eran Elinav, MD, PhD, an immunologist and microbiome researcher at the Weizmann Institute of Science, Rehovot, Israel, observed that these sweeteners affect the microbiome of mice in ways that could affect glycemic responses.
They have now confirmed this observation in a randomized controlled trial with 120 healthy adults.
Each sweetener “significantly and distinctly” altered stool and oral microbiome, and two of them (saccharin and sucralose) significantly impaired glucose tolerance, the researchers reported.
“Importantly, by performing extensive fecal transplantation of human microbiomes into germ-free mice, we demonstrate a causal and individualized link between NNS-altered microbiomes and glucose intolerance developing in non–NNS-consuming recipient mice,” they said.
They noted that the effects of these sweeteners will likely vary from person to person because of the unique composition of an individual’s microbiome.
“We need to raise awareness of the fact that NNS are not inert to the human body as we originally believed. With that said, the clinical health implications of the changes they may elicit in humans remain unknown and merit future long-term studies,” Dr. Elinav said in a news release.
For now, Dr. Elinav said it’s his personal view that “drinking only water seems to be the best solution.”
Weighing the evidence
Several experts weighed in on the results in a statement from the U.K. nonprofit organization, Science Media Centre.
Duane Mellor, PhD, RD, RNutr, registered dietitian and senior teaching fellow, Aston University, Birmingham, England, notes that the study does not show a link between all NNS and higher blood glucose levels in the long term (only after a glucose tolerance test).
“It did suggest, though, that some individuals who do not normally consume sweeteners may not tolerate glucose as well after consuming six sachets of either saccharin or sucralose mixed with glucose per day,” Dr. Mellor says.
Kim Barrett, PhD, distinguished professor of physiology and membrane biology, University of California, Davis, concurs, saying “this well-designed study indicates the potential for NNS to have adverse effects in at least some individuals.”
The study also does not provide any information about how people who normally consume sweeteners or people with either type 1 or type 2 diabetes respond to NNS.
“Therefore, for some people, it is likely to be a better option and more sustainable approach to use sweeteners as a ‘stepping stone’ allowing them to reduce the amount of added sugar in foods and drinks, to reduce their sugar intake and still enjoy what they eat and drink, on the way to reducing both added sugar and sweeteners in their diet,” Dr. Mellor suggests.
Kevin McConway, PhD, with the Open University, Milton Keynes, England, said it’s “important to understand that the research is not saying that these sweeteners are worse for us, in heath terms, than sugar.
“But exactly what the health consequences of all this, if any, might be is a subject for future research,” Dr. McConway added.
Kathy Redfern, PhD, lecturer in human nutrition, University of Plymouth (England) agrees.
“We still have a lot to learn about the human microbiome, and although this study suggests two of the sweeteners tested in this study (sucralose and saccharin) significantly affected glucose tolerance, these deviations were small,” she says.
The International Sweeteners Association also weighs in, saying, “No conclusions about the effects of low/no calorie sweeteners on glucose control or overall health can be extrapolated from this study for the general population or for people who typically consume sweeteners, including people living with diabetes.”
They add “a recent review of the literature concluded that there is clear evidence that changes in the diet unrelated to low/no calorie sweeteners consumption are likely the major determinants of change in gut microbiota.”
Nevertheless, Dr. Redfern says the results “warrant further investigation to assess how small changes in glucose tolerance in response to NNS consumption may influence longer-term glucose tolerance and risk for metabolic complications, such as type 2 diabetes.”
The study had no specific funding. Dr. Elinav is a scientific founder of DayTwo and BiomX, a paid consultant to Hello Inside and Aposense, and a member of the scientific advisory board of Cell. Dr. Mellor has provided consultancy to the International Sweetener Agency and has worked on projects funded by the Food Standards Agency that investigated the health effects of aspartame. Dr. Barrett, Dr. McConway, and Dr. Redfern report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
This article was updated 8/29/22.