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Heavy drinking in your 20s has lasting impact on cancer risk
according to a new study from Australia.
Although alcohol is a known risk factor for cancer, people generally do not expect their heavy drinking in early adulthood to affect their cancer risk many years later, lead author Harindra Jayasekara, MBBS, MD, PhD, with Cancer Council Victoria and University of Melbourne, said in an interview. But in this analysis, “we found evidence consistent with early initiation and chronic progression of carcinogenesis linked to alcohol and its toxic metabolites.”
The study, published online Feb. 19 in the International Journal of Cancer, assessed lifetime drinking trajectories and risk for alcohol-related cancer using data from 22,756 women and 15,701 men recruited to the prospective Melbourne Collaborative Cohort Study from 1990-1994. Heavy drinking was considered an average alcohol intake of at least 60 g/day, which is equivalent to the alcohol content in 6 standard drinks.
During 485,525 person-years of follow-up among women, 2,303 incident alcohol-related cancers were diagnosed, most commonly breast (64%) and colorectal cancer (31%).
During 303,218 person-years of follow-up among men, 789 alcohol-related cancers were found, most commonly colorectal cancer (83%).
The researchers identified three distinct lifetime alcohol intake trajectories for women – lifetime abstainer (39%), stable light (54%), and increasing moderate (7%) – and six for men – lifetime abstainer (14.3%), stable light (51.5%), stable moderate (20.4%), increasing heavy (6.6%), early decreasing heavy (5.1%), and late decreasing heavy (2.2%).
Almost three times more, women were lifetime abstainers (39% vs. 14% of men). And approximately the same percentage of men and women increased their alcohol consumption over time. About 7% of men were classified as increasing heavy drinkers, consuming a moderate amount of alcohol (30-59 g/day) at age 20-39 and increasing their intake markedly from age 40-49 (over 60 g/day) before reducing it by age 60-69. Among women, 7% were classified as increasing moderate, tending to consume around 20 g/day at age 20-29 and gradually increasing their alcohol intake over time to consume close to 40 g/day at age 50-59.
Among men, the early decreasing heavy group started as heavy drinkers at age 20-39 (greater than or equal to 60 g/day) and continued to cut down their intake over time until developing stable light drinking habits by age 60-69, whereas late decreasing heavy drinks continued to drink a lot until age 60-69 before cutting their intake in their 70s.
Impact on cancer risk
For men, relative to lifetime abstention, heavy drinking trajectories were associated with an increased risk for alcohol-related cancer overall.
The strongest associations were for the early decreasing heavy trajectory (hazard ratio, 1.75) and the late decreasing heavy trajectory (HR, 1.94), with the increasing heavy trajectory not far behind (HR, 1.45).
The strength of these associations did not change appreciably in analyses excluding current smokers at baseline.
Among men, the early decreasing heavy and late decreasing heavy intake trajectories were similarly associated with an increased risk for colorectal cancer (HR, 1.56 for early, and HR, 1.74 for late). The corresponding HR for the increasing heavy trajectory was 1.36.
For women, compared with lifetime abstention, the alcohol intake trajectory classified as increasing moderate (30-59 g/day) was associated with a greater risk for alcohol-related cancer overall (HR, 1.25). The strength of this association weakened slightly when current smokers were excluded.
Compared with lifetime abstention, the increasing moderate trajectory in women was similarly associated with an increased risk for breast cancer (HR, 1.30) and colorectal cancer (HR, 1.23).
The 2018 World Cancer Research Fund and American Institute for Cancer Research global cancer prevention recommendation on alcohol is to “avoid any alcohol,” study investigator Julie Bassett, PhD, MSc, with Cancer Council Victoria, said in an interview. “As much as it is important to limit alcohol intake during middle age to prevent cancer, we have shown that limiting intake during early adulthood is also important.”
‘Striking’ findings
Reached for comment, Timothy Brennan, MD, MPH, chief of clinical services at the Addiction Institute of Mount Sinai in New York, said it is “striking” that heavy drinking in early adulthood led to an increased risk for alcohol-related cancers, even among people who drank much less in middle age.
“We’ve known for decades that alcohol is not harmless, but this data adds to the growing body of literature regarding the significant dangers of heavy drinking during early adulthood,” said Dr. Brennan, who wasn’t involved in the study.
Dr. Brennan cautioned, however, that the authors studied alcohol-related cancers, and “there are likely many other [cancer] risk factors that were not analyzed in this dataset.”
Nevertheless, this evidence helps counter the “troubling narrative” that “it is somehow normal and safe to drink excessively in young adulthood.”
“It is most certainly not safe,” Dr. Brennan told this news organization . “We see in this study that drinking excessively in young adulthood can raise the risk of cancer much later in life.”
The study had no commercial funding. Dr. Bassett, Dr. Jayasekara, and Dr. Brennan have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
according to a new study from Australia.
Although alcohol is a known risk factor for cancer, people generally do not expect their heavy drinking in early adulthood to affect their cancer risk many years later, lead author Harindra Jayasekara, MBBS, MD, PhD, with Cancer Council Victoria and University of Melbourne, said in an interview. But in this analysis, “we found evidence consistent with early initiation and chronic progression of carcinogenesis linked to alcohol and its toxic metabolites.”
The study, published online Feb. 19 in the International Journal of Cancer, assessed lifetime drinking trajectories and risk for alcohol-related cancer using data from 22,756 women and 15,701 men recruited to the prospective Melbourne Collaborative Cohort Study from 1990-1994. Heavy drinking was considered an average alcohol intake of at least 60 g/day, which is equivalent to the alcohol content in 6 standard drinks.
During 485,525 person-years of follow-up among women, 2,303 incident alcohol-related cancers were diagnosed, most commonly breast (64%) and colorectal cancer (31%).
During 303,218 person-years of follow-up among men, 789 alcohol-related cancers were found, most commonly colorectal cancer (83%).
The researchers identified three distinct lifetime alcohol intake trajectories for women – lifetime abstainer (39%), stable light (54%), and increasing moderate (7%) – and six for men – lifetime abstainer (14.3%), stable light (51.5%), stable moderate (20.4%), increasing heavy (6.6%), early decreasing heavy (5.1%), and late decreasing heavy (2.2%).
Almost three times more, women were lifetime abstainers (39% vs. 14% of men). And approximately the same percentage of men and women increased their alcohol consumption over time. About 7% of men were classified as increasing heavy drinkers, consuming a moderate amount of alcohol (30-59 g/day) at age 20-39 and increasing their intake markedly from age 40-49 (over 60 g/day) before reducing it by age 60-69. Among women, 7% were classified as increasing moderate, tending to consume around 20 g/day at age 20-29 and gradually increasing their alcohol intake over time to consume close to 40 g/day at age 50-59.
Among men, the early decreasing heavy group started as heavy drinkers at age 20-39 (greater than or equal to 60 g/day) and continued to cut down their intake over time until developing stable light drinking habits by age 60-69, whereas late decreasing heavy drinks continued to drink a lot until age 60-69 before cutting their intake in their 70s.
Impact on cancer risk
For men, relative to lifetime abstention, heavy drinking trajectories were associated with an increased risk for alcohol-related cancer overall.
The strongest associations were for the early decreasing heavy trajectory (hazard ratio, 1.75) and the late decreasing heavy trajectory (HR, 1.94), with the increasing heavy trajectory not far behind (HR, 1.45).
The strength of these associations did not change appreciably in analyses excluding current smokers at baseline.
Among men, the early decreasing heavy and late decreasing heavy intake trajectories were similarly associated with an increased risk for colorectal cancer (HR, 1.56 for early, and HR, 1.74 for late). The corresponding HR for the increasing heavy trajectory was 1.36.
For women, compared with lifetime abstention, the alcohol intake trajectory classified as increasing moderate (30-59 g/day) was associated with a greater risk for alcohol-related cancer overall (HR, 1.25). The strength of this association weakened slightly when current smokers were excluded.
Compared with lifetime abstention, the increasing moderate trajectory in women was similarly associated with an increased risk for breast cancer (HR, 1.30) and colorectal cancer (HR, 1.23).
The 2018 World Cancer Research Fund and American Institute for Cancer Research global cancer prevention recommendation on alcohol is to “avoid any alcohol,” study investigator Julie Bassett, PhD, MSc, with Cancer Council Victoria, said in an interview. “As much as it is important to limit alcohol intake during middle age to prevent cancer, we have shown that limiting intake during early adulthood is also important.”
‘Striking’ findings
Reached for comment, Timothy Brennan, MD, MPH, chief of clinical services at the Addiction Institute of Mount Sinai in New York, said it is “striking” that heavy drinking in early adulthood led to an increased risk for alcohol-related cancers, even among people who drank much less in middle age.
“We’ve known for decades that alcohol is not harmless, but this data adds to the growing body of literature regarding the significant dangers of heavy drinking during early adulthood,” said Dr. Brennan, who wasn’t involved in the study.
Dr. Brennan cautioned, however, that the authors studied alcohol-related cancers, and “there are likely many other [cancer] risk factors that were not analyzed in this dataset.”
Nevertheless, this evidence helps counter the “troubling narrative” that “it is somehow normal and safe to drink excessively in young adulthood.”
“It is most certainly not safe,” Dr. Brennan told this news organization . “We see in this study that drinking excessively in young adulthood can raise the risk of cancer much later in life.”
The study had no commercial funding. Dr. Bassett, Dr. Jayasekara, and Dr. Brennan have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
according to a new study from Australia.
Although alcohol is a known risk factor for cancer, people generally do not expect their heavy drinking in early adulthood to affect their cancer risk many years later, lead author Harindra Jayasekara, MBBS, MD, PhD, with Cancer Council Victoria and University of Melbourne, said in an interview. But in this analysis, “we found evidence consistent with early initiation and chronic progression of carcinogenesis linked to alcohol and its toxic metabolites.”
The study, published online Feb. 19 in the International Journal of Cancer, assessed lifetime drinking trajectories and risk for alcohol-related cancer using data from 22,756 women and 15,701 men recruited to the prospective Melbourne Collaborative Cohort Study from 1990-1994. Heavy drinking was considered an average alcohol intake of at least 60 g/day, which is equivalent to the alcohol content in 6 standard drinks.
During 485,525 person-years of follow-up among women, 2,303 incident alcohol-related cancers were diagnosed, most commonly breast (64%) and colorectal cancer (31%).
During 303,218 person-years of follow-up among men, 789 alcohol-related cancers were found, most commonly colorectal cancer (83%).
The researchers identified three distinct lifetime alcohol intake trajectories for women – lifetime abstainer (39%), stable light (54%), and increasing moderate (7%) – and six for men – lifetime abstainer (14.3%), stable light (51.5%), stable moderate (20.4%), increasing heavy (6.6%), early decreasing heavy (5.1%), and late decreasing heavy (2.2%).
Almost three times more, women were lifetime abstainers (39% vs. 14% of men). And approximately the same percentage of men and women increased their alcohol consumption over time. About 7% of men were classified as increasing heavy drinkers, consuming a moderate amount of alcohol (30-59 g/day) at age 20-39 and increasing their intake markedly from age 40-49 (over 60 g/day) before reducing it by age 60-69. Among women, 7% were classified as increasing moderate, tending to consume around 20 g/day at age 20-29 and gradually increasing their alcohol intake over time to consume close to 40 g/day at age 50-59.
Among men, the early decreasing heavy group started as heavy drinkers at age 20-39 (greater than or equal to 60 g/day) and continued to cut down their intake over time until developing stable light drinking habits by age 60-69, whereas late decreasing heavy drinks continued to drink a lot until age 60-69 before cutting their intake in their 70s.
Impact on cancer risk
For men, relative to lifetime abstention, heavy drinking trajectories were associated with an increased risk for alcohol-related cancer overall.
The strongest associations were for the early decreasing heavy trajectory (hazard ratio, 1.75) and the late decreasing heavy trajectory (HR, 1.94), with the increasing heavy trajectory not far behind (HR, 1.45).
The strength of these associations did not change appreciably in analyses excluding current smokers at baseline.
Among men, the early decreasing heavy and late decreasing heavy intake trajectories were similarly associated with an increased risk for colorectal cancer (HR, 1.56 for early, and HR, 1.74 for late). The corresponding HR for the increasing heavy trajectory was 1.36.
For women, compared with lifetime abstention, the alcohol intake trajectory classified as increasing moderate (30-59 g/day) was associated with a greater risk for alcohol-related cancer overall (HR, 1.25). The strength of this association weakened slightly when current smokers were excluded.
Compared with lifetime abstention, the increasing moderate trajectory in women was similarly associated with an increased risk for breast cancer (HR, 1.30) and colorectal cancer (HR, 1.23).
The 2018 World Cancer Research Fund and American Institute for Cancer Research global cancer prevention recommendation on alcohol is to “avoid any alcohol,” study investigator Julie Bassett, PhD, MSc, with Cancer Council Victoria, said in an interview. “As much as it is important to limit alcohol intake during middle age to prevent cancer, we have shown that limiting intake during early adulthood is also important.”
‘Striking’ findings
Reached for comment, Timothy Brennan, MD, MPH, chief of clinical services at the Addiction Institute of Mount Sinai in New York, said it is “striking” that heavy drinking in early adulthood led to an increased risk for alcohol-related cancers, even among people who drank much less in middle age.
“We’ve known for decades that alcohol is not harmless, but this data adds to the growing body of literature regarding the significant dangers of heavy drinking during early adulthood,” said Dr. Brennan, who wasn’t involved in the study.
Dr. Brennan cautioned, however, that the authors studied alcohol-related cancers, and “there are likely many other [cancer] risk factors that were not analyzed in this dataset.”
Nevertheless, this evidence helps counter the “troubling narrative” that “it is somehow normal and safe to drink excessively in young adulthood.”
“It is most certainly not safe,” Dr. Brennan told this news organization . “We see in this study that drinking excessively in young adulthood can raise the risk of cancer much later in life.”
The study had no commercial funding. Dr. Bassett, Dr. Jayasekara, and Dr. Brennan have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM THE INTERNATIONAL JOURNAL OF CANCER
First ‘before-and-after’ COVID-19 brain imaging study shows structural changes
, a new imaging study shows.
In the first study to use magnetic resonance brain imaging, before and after COVID-19, investigators found “greater reduction in grey matter thickness and tissue-contrast in the orbitofrontal cortex and parahippocampal gyrus, greater changes in markers of tissue damage in regions functionally connected to the primary olfactory cortex and greater reduction in global brain size.” However, the researchers urge caution when interpreting the findings.
Gwenaëlle Douaud, PhD, Wellcome Center for Integrative Neuroimaging, Nuffield Department of Clinical Neurosciences, University of Oxford, England, and colleagues describe these brain changes as “modest.”
“Whether these abnormal changes are the hallmark of the spread of the pathogenic effects in the brain, or of the virus itself, and whether these may prefigure a future vulnerability of the limbic system in particular, including memory, for these participants, remains to be investigated,” the researchers wrote.
The findings were published online March 7 in the journal Nature.
Gray matter loss
The investigators analyzed data from the UK Biobank, a large-scale biomedical database with genetic and health information for about 500,000 individuals living in the UK. They identified 785 adults aged 51-81 years who had undergone two brain MRIs about 3 years apart. Of these, 401 tested positive for SARS-CoV-2 before the second scan.
Participants also completed cognitive tests at the time of both scans.
Biobank centers use identical MRI scans and scanning methods, including six types of MRI scans, to image distinct regions of the brain and brain function. Results showed that although some loss of gray matter over time is normal, individuals who were infected with SARS-CoV-2 showed a 0.2% to 2% brain tissue loss in the parahippocampal gyrus, the orbitofrontal cortex, and the insula – all of which are largely involved in the sense of smell.
Participants who had contracted COVID-19 also showed a greater reduction in overall brain volume and a decrease in cognitive function.
Most of those with COVID-19 had only mild or moderate symptoms. However, the findings held even after the researchers excluded patients who had been hospitalized.
More research needed
“These findings might help explain why some people experience brain symptoms long after the acute infection,” Max Taquet, PhD, National Institute for Health Research Oxford Health BRC senior research fellow, University of Oxford, said in a press release.
Dr. Taquet, who was not a part of the study, noted the causes of these brain changes remain to be determined. Questions remain as to “whether they can be prevented or even reverted, as well as whether similar changes are observed in hospitalized patients,” children, younger adults, and minority groups.
“It is possible that these brain changes are not caused by COVID-19 but represent the natural progression of a disease that itself increased the risk of COVID-19,” Dr. Taquet said.
Other experts expressed concern over the findings and emphasized the need for more research.
“I am very concerned by the alarming use of language in the report with terms such as ‘neurodegenerative,’ “ Alan Carson, MD, professor of neuropsychiatry at the Center for Clinical Brain Sciences at the University of Edinburgh, Scotland, said in a press release. “The size and magnitude of brain changes found is very modest and such changes can be caused by a simple change in mental experience,” Dr. Carson said.
“What this study almost certainly shows is the impact, in terms of neural changes, of being disconnected from one’s sense of smell,” he added.
The study was funded by the Wellcome Trust Collaborative. Full financial conflict information for the study authors is included in the original article. Dr. Taquet has collaborated previously with some of the investigators.
A version of this article first appeared on Medscape.com.
, a new imaging study shows.
In the first study to use magnetic resonance brain imaging, before and after COVID-19, investigators found “greater reduction in grey matter thickness and tissue-contrast in the orbitofrontal cortex and parahippocampal gyrus, greater changes in markers of tissue damage in regions functionally connected to the primary olfactory cortex and greater reduction in global brain size.” However, the researchers urge caution when interpreting the findings.
Gwenaëlle Douaud, PhD, Wellcome Center for Integrative Neuroimaging, Nuffield Department of Clinical Neurosciences, University of Oxford, England, and colleagues describe these brain changes as “modest.”
“Whether these abnormal changes are the hallmark of the spread of the pathogenic effects in the brain, or of the virus itself, and whether these may prefigure a future vulnerability of the limbic system in particular, including memory, for these participants, remains to be investigated,” the researchers wrote.
The findings were published online March 7 in the journal Nature.
Gray matter loss
The investigators analyzed data from the UK Biobank, a large-scale biomedical database with genetic and health information for about 500,000 individuals living in the UK. They identified 785 adults aged 51-81 years who had undergone two brain MRIs about 3 years apart. Of these, 401 tested positive for SARS-CoV-2 before the second scan.
Participants also completed cognitive tests at the time of both scans.
Biobank centers use identical MRI scans and scanning methods, including six types of MRI scans, to image distinct regions of the brain and brain function. Results showed that although some loss of gray matter over time is normal, individuals who were infected with SARS-CoV-2 showed a 0.2% to 2% brain tissue loss in the parahippocampal gyrus, the orbitofrontal cortex, and the insula – all of which are largely involved in the sense of smell.
Participants who had contracted COVID-19 also showed a greater reduction in overall brain volume and a decrease in cognitive function.
Most of those with COVID-19 had only mild or moderate symptoms. However, the findings held even after the researchers excluded patients who had been hospitalized.
More research needed
“These findings might help explain why some people experience brain symptoms long after the acute infection,” Max Taquet, PhD, National Institute for Health Research Oxford Health BRC senior research fellow, University of Oxford, said in a press release.
Dr. Taquet, who was not a part of the study, noted the causes of these brain changes remain to be determined. Questions remain as to “whether they can be prevented or even reverted, as well as whether similar changes are observed in hospitalized patients,” children, younger adults, and minority groups.
“It is possible that these brain changes are not caused by COVID-19 but represent the natural progression of a disease that itself increased the risk of COVID-19,” Dr. Taquet said.
Other experts expressed concern over the findings and emphasized the need for more research.
“I am very concerned by the alarming use of language in the report with terms such as ‘neurodegenerative,’ “ Alan Carson, MD, professor of neuropsychiatry at the Center for Clinical Brain Sciences at the University of Edinburgh, Scotland, said in a press release. “The size and magnitude of brain changes found is very modest and such changes can be caused by a simple change in mental experience,” Dr. Carson said.
“What this study almost certainly shows is the impact, in terms of neural changes, of being disconnected from one’s sense of smell,” he added.
The study was funded by the Wellcome Trust Collaborative. Full financial conflict information for the study authors is included in the original article. Dr. Taquet has collaborated previously with some of the investigators.
A version of this article first appeared on Medscape.com.
, a new imaging study shows.
In the first study to use magnetic resonance brain imaging, before and after COVID-19, investigators found “greater reduction in grey matter thickness and tissue-contrast in the orbitofrontal cortex and parahippocampal gyrus, greater changes in markers of tissue damage in regions functionally connected to the primary olfactory cortex and greater reduction in global brain size.” However, the researchers urge caution when interpreting the findings.
Gwenaëlle Douaud, PhD, Wellcome Center for Integrative Neuroimaging, Nuffield Department of Clinical Neurosciences, University of Oxford, England, and colleagues describe these brain changes as “modest.”
“Whether these abnormal changes are the hallmark of the spread of the pathogenic effects in the brain, or of the virus itself, and whether these may prefigure a future vulnerability of the limbic system in particular, including memory, for these participants, remains to be investigated,” the researchers wrote.
The findings were published online March 7 in the journal Nature.
Gray matter loss
The investigators analyzed data from the UK Biobank, a large-scale biomedical database with genetic and health information for about 500,000 individuals living in the UK. They identified 785 adults aged 51-81 years who had undergone two brain MRIs about 3 years apart. Of these, 401 tested positive for SARS-CoV-2 before the second scan.
Participants also completed cognitive tests at the time of both scans.
Biobank centers use identical MRI scans and scanning methods, including six types of MRI scans, to image distinct regions of the brain and brain function. Results showed that although some loss of gray matter over time is normal, individuals who were infected with SARS-CoV-2 showed a 0.2% to 2% brain tissue loss in the parahippocampal gyrus, the orbitofrontal cortex, and the insula – all of which are largely involved in the sense of smell.
Participants who had contracted COVID-19 also showed a greater reduction in overall brain volume and a decrease in cognitive function.
Most of those with COVID-19 had only mild or moderate symptoms. However, the findings held even after the researchers excluded patients who had been hospitalized.
More research needed
“These findings might help explain why some people experience brain symptoms long after the acute infection,” Max Taquet, PhD, National Institute for Health Research Oxford Health BRC senior research fellow, University of Oxford, said in a press release.
Dr. Taquet, who was not a part of the study, noted the causes of these brain changes remain to be determined. Questions remain as to “whether they can be prevented or even reverted, as well as whether similar changes are observed in hospitalized patients,” children, younger adults, and minority groups.
“It is possible that these brain changes are not caused by COVID-19 but represent the natural progression of a disease that itself increased the risk of COVID-19,” Dr. Taquet said.
Other experts expressed concern over the findings and emphasized the need for more research.
“I am very concerned by the alarming use of language in the report with terms such as ‘neurodegenerative,’ “ Alan Carson, MD, professor of neuropsychiatry at the Center for Clinical Brain Sciences at the University of Edinburgh, Scotland, said in a press release. “The size and magnitude of brain changes found is very modest and such changes can be caused by a simple change in mental experience,” Dr. Carson said.
“What this study almost certainly shows is the impact, in terms of neural changes, of being disconnected from one’s sense of smell,” he added.
The study was funded by the Wellcome Trust Collaborative. Full financial conflict information for the study authors is included in the original article. Dr. Taquet has collaborated previously with some of the investigators.
A version of this article first appeared on Medscape.com.
From Nature
Filling opioid prescriptions akin to a Sisyphean task
Pain management is a huge part of how we in palliative care help patients – and most of the time, I think we do it well, but in the regulatory environment of the opioid epidemic,
A patient – let’s call her Joan – calls me in distress. She is a 62-year-old woman with widespread metastatic breast cancer. Her pain is mainly due to bone metastases, but she also has discomfort due to the cancer’s invasion of the thin membranes that line her lungs and abdomen.
She was started on a combination opioid and acetaminophen tablet about 2 months ago by her oncologist, but is now requiring it around the clock, nearing the ceiling dose for this particular medication.
Given that her pain is escalating, Joan and I discuss starting a long-acting opioid to better manage the peak and trough effect of short-acting opioids, which can make a patient feel that the pain is relieved only for a few hours at a time, with sharp spikes throughout the day that mandate the next dose of short-acting opioid. This tethers the patient to the clock, having to take as many as six or eight doses of medication per day, and can be very disruptive to daily life.
I send an e-prescription for the same opioid Joan’s currently taking, but in a long-acting format that will slow-release over 8-10 hours, relieving her of the need to take a medication every 3-4 hours. I have learned over the years that nearly every long-acting opioid automatically generates a prior authorization request from the patient’s insurance company and so I immediately email our prior authorization team to submit to Joan’s insurance right away to avoid this extra delay.
Our prior authorization team is exceptionally responsive and submits these requests with urgency every time – they understand that cancer pain is a serious problem and we can’t wait 5 business days for answers. They are typically able to obtain an approved prior authorization for nearly every long-acting opioid I write within 24-48 hours.
But here’s where things go sideways.
First, the insurance company denies the prior authorization request, demanding that I revise the prescription from the long-acting version of the opioid she is currently taking to a cheaper, older opioid that she’s never tried before. In other words, they won’t cover the drug I requested without Joan first trying a completely different drug and failing it. This only makes sense for the insurance company’s bottom line – it makes no clinical sense at all. Why would I try a novel compound that Joan’s never had and one to which I have no idea how she’ll respond when I could keep her on the same compound knowing that she tolerates it just fine?
Past experience tells me insurance companies rarely budge on this, and appealing the decision would just introduce even more delay of care, so I begrudgingly change the prescription and send it again to the pharmacy. I message Joan to let her know that her insurance won’t cover my drug of choice and that we have to try this older one first.
A few hours later, Joan sends me a message: “My pharmacy says it’s going to take A WEEK to get the long-acting medicine!”
In the meantime, Joan has been using her short-acting opioid faster than anticipated because of her escalating pain – so she’s now running low on that as well.
I write for more of her short-acting opioid and e-script it to her pharmacy.
Within a few hours, we get another automatic response from her insurance that we’re going to need a prior authorization for additional short-acting opioid because she’s exceeded “quantity limitations,” which as far as I can tell is a completely arbitrary number not based on clinical evidence.
The prior auth team jumps on it and submits to override the quantity limit – successfully – and sends the override code to her pharmacy to reprocess the prescription.
But now the pharmacist tells Joan that they won’t fill the Rx anyway because it’s “too early.” They tell her that “state laws” prevent them from filling the scrip.
Is this true? I have no idea. I’m not an expert on California pharmacy law. All I know is that my patient is in pain and something needs to happen quickly.
I write for a second short-acting opioid – again a completely different compound. Ironically, this Rx goes through instantly without need for prior authorization. But now Joan has to switch to another new drug for no good medical reason.
If you’re still with me this far into the weeds, I’m grateful. In all it took a combined 4 hours of work (between myself and the prior auth team) to get two opioid Rx’s filled – and these were completely different medications than the ones I originally wrote for. I also had to move her prescriptions to the hospital’s pharmacy (another inconvenience for Joan and her family) so that she could get the medications in a timely manner. All this work to ensure that a single patient had adequate and timely pain relief and to prevent her from having to make an unnecessary visit to the emergency department for pain crisis.
This is just a regular day in outpatient palliative care in the era of the opioid epidemic.
The epidemic has caused tremendous pain and suffering for millions of people over the past 2 decades – namely those lost to opioid overdoses and their loved ones. And for the most part, tightening access to opioids for routine aches and pains among a relatively healthy population is not wrong, in my opinion, as long as those restrictions are based in good faith on robust evidence.
But the hidden cost of the Centers for Disease Control and Prevention’s 2016 opioid prescribing guidelines for nonmalignant pain, as well as the flurry of restrictive state laws they generated, is felt every day by patients with serious illness even though the guidelines were never meant to affect them. Patients with active cancer, receiving palliative care services, or at the end of life, were supposed to be exempted from these guidelines since good evidence supports the use of opioids in these populations.
Instead of preserving access to desperately needed pain medicine for those suffering with serious illness, states and insurers have aggressively sought to gatekeep opioids from everyone, resulting in stigma, delays, and needless suffering.
Several recent studies have revealed the effects of this gatekeeping on patients with cancer.
A qualitative study with 26 advanced cancer patients described the demoralization and stigma many patients felt when taking opioids, which they directly tied to media messaging around the opioid epidemic. Even when they reluctantly agreed to take opioids to treat cancer-related pain, there were systemic impediments to achieving adequate pain relief – similar to my experience with Joan – that were directly caused by insurance and pharmacy constraints.
Those of us who care for oncology patients also appear to be undertreating cancer-related pain. Another recent study that found the amount of opioid medications prescribed to an advanced cancer patient near the end of life dropped by 38% between 2007 and 2017. The authors suggest that a direct consequence of this decline in appropriate opioid prescribing is an observed 50% rise in emergency department visits over the same time period by cancer patients for pain-related reasons.
This makes sense – if patients aren’t routinely prescribed the opioids they need to manage their cancer-related pain; or, if the stigma against using opioids is so harsh that it causes patients to shun opioids; or, if there are so many system barriers in place to prevent patients from obtaining opioids in a timely manner – then patients’ pain will crescendo, leaving them with little alternative but to head to the emergency department.
This undertreatment is corroborated by another study that examined data from the Centers for Medicare & Medicaid Services Part D prescriber database between 2013 and 2017, finding that both oncologists and nononcologists prescribed about 21% fewer opioids to Medicare beneficiaries during that time, compared with the period prior to 2013.
Interestingly, the researchers also found that opioid prescribing by palliative care providers increased by 15% over the same period. On a positive note, this suggests the presence of a growing outpatient palliative care workforce. But it may also reflect growing unease among oncologists with the perceived liability for prescribing opioids and a desire to ask other specialists to take on this liability. At the same time, it may reflect the very real and ever-increasing administrative burden associated with prescribing opioids and the fact that busy oncologists may not have time to spend on this aspect of cancer care. Thus, as palliative care clinicians become more visible and numerous in the outpatient arena, oncologists may increasingly ask palliative care clinicians like myself to take this on.
The problem with this is that merely handing off the administrative burden to another clinician doesn’t address the underlying problem. Anecdotal evidence suggests (and my own experiences corroborate) this administrative burden can cause real harm. A survey of 1,000 physicians conducted by the American Medical Association in 2021 found that 93% of respondents reported a delay in patient care due to prior authorization burden and 34% of respondents reported that their patients had suffered a “serious adverse event” due to prior authorization requirements.
The CDC recently announced it will take steps to revise the 2016 opioid prescribing guidelines for chronic pain after hearing from members of the medical community as well as patients living with chronic pain about the harsh, unintended consequences of the guidelines. I can only hope that insurance companies will follow suit, revising their opioid prior authorization requirements to finally come into alignment with the rational, safe use of opioids in patients with advanced cancer. It’s too bad that any improvement in the future will be too late for the millions of patients who have suffered irreversible iatrogenic harms due to delays in achieving adequate pain relief.
Sarah F. D’Ambruoso, NP, is a palliative care nurse practitioner in Santa Monica, Calif.
Pain management is a huge part of how we in palliative care help patients – and most of the time, I think we do it well, but in the regulatory environment of the opioid epidemic,
A patient – let’s call her Joan – calls me in distress. She is a 62-year-old woman with widespread metastatic breast cancer. Her pain is mainly due to bone metastases, but she also has discomfort due to the cancer’s invasion of the thin membranes that line her lungs and abdomen.
She was started on a combination opioid and acetaminophen tablet about 2 months ago by her oncologist, but is now requiring it around the clock, nearing the ceiling dose for this particular medication.
Given that her pain is escalating, Joan and I discuss starting a long-acting opioid to better manage the peak and trough effect of short-acting opioids, which can make a patient feel that the pain is relieved only for a few hours at a time, with sharp spikes throughout the day that mandate the next dose of short-acting opioid. This tethers the patient to the clock, having to take as many as six or eight doses of medication per day, and can be very disruptive to daily life.
I send an e-prescription for the same opioid Joan’s currently taking, but in a long-acting format that will slow-release over 8-10 hours, relieving her of the need to take a medication every 3-4 hours. I have learned over the years that nearly every long-acting opioid automatically generates a prior authorization request from the patient’s insurance company and so I immediately email our prior authorization team to submit to Joan’s insurance right away to avoid this extra delay.
Our prior authorization team is exceptionally responsive and submits these requests with urgency every time – they understand that cancer pain is a serious problem and we can’t wait 5 business days for answers. They are typically able to obtain an approved prior authorization for nearly every long-acting opioid I write within 24-48 hours.
But here’s where things go sideways.
First, the insurance company denies the prior authorization request, demanding that I revise the prescription from the long-acting version of the opioid she is currently taking to a cheaper, older opioid that she’s never tried before. In other words, they won’t cover the drug I requested without Joan first trying a completely different drug and failing it. This only makes sense for the insurance company’s bottom line – it makes no clinical sense at all. Why would I try a novel compound that Joan’s never had and one to which I have no idea how she’ll respond when I could keep her on the same compound knowing that she tolerates it just fine?
Past experience tells me insurance companies rarely budge on this, and appealing the decision would just introduce even more delay of care, so I begrudgingly change the prescription and send it again to the pharmacy. I message Joan to let her know that her insurance won’t cover my drug of choice and that we have to try this older one first.
A few hours later, Joan sends me a message: “My pharmacy says it’s going to take A WEEK to get the long-acting medicine!”
In the meantime, Joan has been using her short-acting opioid faster than anticipated because of her escalating pain – so she’s now running low on that as well.
I write for more of her short-acting opioid and e-script it to her pharmacy.
Within a few hours, we get another automatic response from her insurance that we’re going to need a prior authorization for additional short-acting opioid because she’s exceeded “quantity limitations,” which as far as I can tell is a completely arbitrary number not based on clinical evidence.
The prior auth team jumps on it and submits to override the quantity limit – successfully – and sends the override code to her pharmacy to reprocess the prescription.
But now the pharmacist tells Joan that they won’t fill the Rx anyway because it’s “too early.” They tell her that “state laws” prevent them from filling the scrip.
Is this true? I have no idea. I’m not an expert on California pharmacy law. All I know is that my patient is in pain and something needs to happen quickly.
I write for a second short-acting opioid – again a completely different compound. Ironically, this Rx goes through instantly without need for prior authorization. But now Joan has to switch to another new drug for no good medical reason.
If you’re still with me this far into the weeds, I’m grateful. In all it took a combined 4 hours of work (between myself and the prior auth team) to get two opioid Rx’s filled – and these were completely different medications than the ones I originally wrote for. I also had to move her prescriptions to the hospital’s pharmacy (another inconvenience for Joan and her family) so that she could get the medications in a timely manner. All this work to ensure that a single patient had adequate and timely pain relief and to prevent her from having to make an unnecessary visit to the emergency department for pain crisis.
This is just a regular day in outpatient palliative care in the era of the opioid epidemic.
The epidemic has caused tremendous pain and suffering for millions of people over the past 2 decades – namely those lost to opioid overdoses and their loved ones. And for the most part, tightening access to opioids for routine aches and pains among a relatively healthy population is not wrong, in my opinion, as long as those restrictions are based in good faith on robust evidence.
But the hidden cost of the Centers for Disease Control and Prevention’s 2016 opioid prescribing guidelines for nonmalignant pain, as well as the flurry of restrictive state laws they generated, is felt every day by patients with serious illness even though the guidelines were never meant to affect them. Patients with active cancer, receiving palliative care services, or at the end of life, were supposed to be exempted from these guidelines since good evidence supports the use of opioids in these populations.
Instead of preserving access to desperately needed pain medicine for those suffering with serious illness, states and insurers have aggressively sought to gatekeep opioids from everyone, resulting in stigma, delays, and needless suffering.
Several recent studies have revealed the effects of this gatekeeping on patients with cancer.
A qualitative study with 26 advanced cancer patients described the demoralization and stigma many patients felt when taking opioids, which they directly tied to media messaging around the opioid epidemic. Even when they reluctantly agreed to take opioids to treat cancer-related pain, there were systemic impediments to achieving adequate pain relief – similar to my experience with Joan – that were directly caused by insurance and pharmacy constraints.
Those of us who care for oncology patients also appear to be undertreating cancer-related pain. Another recent study that found the amount of opioid medications prescribed to an advanced cancer patient near the end of life dropped by 38% between 2007 and 2017. The authors suggest that a direct consequence of this decline in appropriate opioid prescribing is an observed 50% rise in emergency department visits over the same time period by cancer patients for pain-related reasons.
This makes sense – if patients aren’t routinely prescribed the opioids they need to manage their cancer-related pain; or, if the stigma against using opioids is so harsh that it causes patients to shun opioids; or, if there are so many system barriers in place to prevent patients from obtaining opioids in a timely manner – then patients’ pain will crescendo, leaving them with little alternative but to head to the emergency department.
This undertreatment is corroborated by another study that examined data from the Centers for Medicare & Medicaid Services Part D prescriber database between 2013 and 2017, finding that both oncologists and nononcologists prescribed about 21% fewer opioids to Medicare beneficiaries during that time, compared with the period prior to 2013.
Interestingly, the researchers also found that opioid prescribing by palliative care providers increased by 15% over the same period. On a positive note, this suggests the presence of a growing outpatient palliative care workforce. But it may also reflect growing unease among oncologists with the perceived liability for prescribing opioids and a desire to ask other specialists to take on this liability. At the same time, it may reflect the very real and ever-increasing administrative burden associated with prescribing opioids and the fact that busy oncologists may not have time to spend on this aspect of cancer care. Thus, as palliative care clinicians become more visible and numerous in the outpatient arena, oncologists may increasingly ask palliative care clinicians like myself to take this on.
The problem with this is that merely handing off the administrative burden to another clinician doesn’t address the underlying problem. Anecdotal evidence suggests (and my own experiences corroborate) this administrative burden can cause real harm. A survey of 1,000 physicians conducted by the American Medical Association in 2021 found that 93% of respondents reported a delay in patient care due to prior authorization burden and 34% of respondents reported that their patients had suffered a “serious adverse event” due to prior authorization requirements.
The CDC recently announced it will take steps to revise the 2016 opioid prescribing guidelines for chronic pain after hearing from members of the medical community as well as patients living with chronic pain about the harsh, unintended consequences of the guidelines. I can only hope that insurance companies will follow suit, revising their opioid prior authorization requirements to finally come into alignment with the rational, safe use of opioids in patients with advanced cancer. It’s too bad that any improvement in the future will be too late for the millions of patients who have suffered irreversible iatrogenic harms due to delays in achieving adequate pain relief.
Sarah F. D’Ambruoso, NP, is a palliative care nurse practitioner in Santa Monica, Calif.
Pain management is a huge part of how we in palliative care help patients – and most of the time, I think we do it well, but in the regulatory environment of the opioid epidemic,
A patient – let’s call her Joan – calls me in distress. She is a 62-year-old woman with widespread metastatic breast cancer. Her pain is mainly due to bone metastases, but she also has discomfort due to the cancer’s invasion of the thin membranes that line her lungs and abdomen.
She was started on a combination opioid and acetaminophen tablet about 2 months ago by her oncologist, but is now requiring it around the clock, nearing the ceiling dose for this particular medication.
Given that her pain is escalating, Joan and I discuss starting a long-acting opioid to better manage the peak and trough effect of short-acting opioids, which can make a patient feel that the pain is relieved only for a few hours at a time, with sharp spikes throughout the day that mandate the next dose of short-acting opioid. This tethers the patient to the clock, having to take as many as six or eight doses of medication per day, and can be very disruptive to daily life.
I send an e-prescription for the same opioid Joan’s currently taking, but in a long-acting format that will slow-release over 8-10 hours, relieving her of the need to take a medication every 3-4 hours. I have learned over the years that nearly every long-acting opioid automatically generates a prior authorization request from the patient’s insurance company and so I immediately email our prior authorization team to submit to Joan’s insurance right away to avoid this extra delay.
Our prior authorization team is exceptionally responsive and submits these requests with urgency every time – they understand that cancer pain is a serious problem and we can’t wait 5 business days for answers. They are typically able to obtain an approved prior authorization for nearly every long-acting opioid I write within 24-48 hours.
But here’s where things go sideways.
First, the insurance company denies the prior authorization request, demanding that I revise the prescription from the long-acting version of the opioid she is currently taking to a cheaper, older opioid that she’s never tried before. In other words, they won’t cover the drug I requested without Joan first trying a completely different drug and failing it. This only makes sense for the insurance company’s bottom line – it makes no clinical sense at all. Why would I try a novel compound that Joan’s never had and one to which I have no idea how she’ll respond when I could keep her on the same compound knowing that she tolerates it just fine?
Past experience tells me insurance companies rarely budge on this, and appealing the decision would just introduce even more delay of care, so I begrudgingly change the prescription and send it again to the pharmacy. I message Joan to let her know that her insurance won’t cover my drug of choice and that we have to try this older one first.
A few hours later, Joan sends me a message: “My pharmacy says it’s going to take A WEEK to get the long-acting medicine!”
In the meantime, Joan has been using her short-acting opioid faster than anticipated because of her escalating pain – so she’s now running low on that as well.
I write for more of her short-acting opioid and e-script it to her pharmacy.
Within a few hours, we get another automatic response from her insurance that we’re going to need a prior authorization for additional short-acting opioid because she’s exceeded “quantity limitations,” which as far as I can tell is a completely arbitrary number not based on clinical evidence.
The prior auth team jumps on it and submits to override the quantity limit – successfully – and sends the override code to her pharmacy to reprocess the prescription.
But now the pharmacist tells Joan that they won’t fill the Rx anyway because it’s “too early.” They tell her that “state laws” prevent them from filling the scrip.
Is this true? I have no idea. I’m not an expert on California pharmacy law. All I know is that my patient is in pain and something needs to happen quickly.
I write for a second short-acting opioid – again a completely different compound. Ironically, this Rx goes through instantly without need for prior authorization. But now Joan has to switch to another new drug for no good medical reason.
If you’re still with me this far into the weeds, I’m grateful. In all it took a combined 4 hours of work (between myself and the prior auth team) to get two opioid Rx’s filled – and these were completely different medications than the ones I originally wrote for. I also had to move her prescriptions to the hospital’s pharmacy (another inconvenience for Joan and her family) so that she could get the medications in a timely manner. All this work to ensure that a single patient had adequate and timely pain relief and to prevent her from having to make an unnecessary visit to the emergency department for pain crisis.
This is just a regular day in outpatient palliative care in the era of the opioid epidemic.
The epidemic has caused tremendous pain and suffering for millions of people over the past 2 decades – namely those lost to opioid overdoses and their loved ones. And for the most part, tightening access to opioids for routine aches and pains among a relatively healthy population is not wrong, in my opinion, as long as those restrictions are based in good faith on robust evidence.
But the hidden cost of the Centers for Disease Control and Prevention’s 2016 opioid prescribing guidelines for nonmalignant pain, as well as the flurry of restrictive state laws they generated, is felt every day by patients with serious illness even though the guidelines were never meant to affect them. Patients with active cancer, receiving palliative care services, or at the end of life, were supposed to be exempted from these guidelines since good evidence supports the use of opioids in these populations.
Instead of preserving access to desperately needed pain medicine for those suffering with serious illness, states and insurers have aggressively sought to gatekeep opioids from everyone, resulting in stigma, delays, and needless suffering.
Several recent studies have revealed the effects of this gatekeeping on patients with cancer.
A qualitative study with 26 advanced cancer patients described the demoralization and stigma many patients felt when taking opioids, which they directly tied to media messaging around the opioid epidemic. Even when they reluctantly agreed to take opioids to treat cancer-related pain, there were systemic impediments to achieving adequate pain relief – similar to my experience with Joan – that were directly caused by insurance and pharmacy constraints.
Those of us who care for oncology patients also appear to be undertreating cancer-related pain. Another recent study that found the amount of opioid medications prescribed to an advanced cancer patient near the end of life dropped by 38% between 2007 and 2017. The authors suggest that a direct consequence of this decline in appropriate opioid prescribing is an observed 50% rise in emergency department visits over the same time period by cancer patients for pain-related reasons.
This makes sense – if patients aren’t routinely prescribed the opioids they need to manage their cancer-related pain; or, if the stigma against using opioids is so harsh that it causes patients to shun opioids; or, if there are so many system barriers in place to prevent patients from obtaining opioids in a timely manner – then patients’ pain will crescendo, leaving them with little alternative but to head to the emergency department.
This undertreatment is corroborated by another study that examined data from the Centers for Medicare & Medicaid Services Part D prescriber database between 2013 and 2017, finding that both oncologists and nononcologists prescribed about 21% fewer opioids to Medicare beneficiaries during that time, compared with the period prior to 2013.
Interestingly, the researchers also found that opioid prescribing by palliative care providers increased by 15% over the same period. On a positive note, this suggests the presence of a growing outpatient palliative care workforce. But it may also reflect growing unease among oncologists with the perceived liability for prescribing opioids and a desire to ask other specialists to take on this liability. At the same time, it may reflect the very real and ever-increasing administrative burden associated with prescribing opioids and the fact that busy oncologists may not have time to spend on this aspect of cancer care. Thus, as palliative care clinicians become more visible and numerous in the outpatient arena, oncologists may increasingly ask palliative care clinicians like myself to take this on.
The problem with this is that merely handing off the administrative burden to another clinician doesn’t address the underlying problem. Anecdotal evidence suggests (and my own experiences corroborate) this administrative burden can cause real harm. A survey of 1,000 physicians conducted by the American Medical Association in 2021 found that 93% of respondents reported a delay in patient care due to prior authorization burden and 34% of respondents reported that their patients had suffered a “serious adverse event” due to prior authorization requirements.
The CDC recently announced it will take steps to revise the 2016 opioid prescribing guidelines for chronic pain after hearing from members of the medical community as well as patients living with chronic pain about the harsh, unintended consequences of the guidelines. I can only hope that insurance companies will follow suit, revising their opioid prior authorization requirements to finally come into alignment with the rational, safe use of opioids in patients with advanced cancer. It’s too bad that any improvement in the future will be too late for the millions of patients who have suffered irreversible iatrogenic harms due to delays in achieving adequate pain relief.
Sarah F. D’Ambruoso, NP, is a palliative care nurse practitioner in Santa Monica, Calif.
MRI with mammogram reduces breast cancer mortality by more than 50% in high-risk women
Among women with ATM, CHEK2, or PALB2 pathogenic variants, annual MRI screening beginning at age 30 or 35, followed by concomitant MRI and mammography at age 40, could significantly reduce breast cancer mortality, according to a new model.
ATM, CHEK2, and PALB2 are the most common of a more recently discovered group of pathogenic variants that confer a moderate to high risk of breast cancer.
In a study published online Feb. 17, 2022, in JAMA Oncology, researchers used two simulation models and risk estimates from the Cancer Risk Estimates Related to Susceptibility Consortium to predict that MRI screening at age 35 would produce a 54.4%-57.6% reduction in breast cancer mortality, with an estimated 4,661-5,001 false positive screenings and 1,280-1,368 benign biopsies per 1,000 women. At age 30, the model predicted 55.4-59.5% reduction in risk, 5,075-5,415 false positives, and 1,439-1,528 benign biopsies. Annual mammography at age 40 alone could reduce risk by 36%-39%.
The false positives and benign biopsies represent cumulative lifetime results.
“We’ve known for a long time that mammography is less sensitive in younger women than in older women and, of course, when women have a genetic predisposition, we’re very concerned about early-onset cancer. We’ve also known that when you do MRI at the same time as mammography, you find a lot more cancers. [There are] more false positives, but there is clearly a greater yield of cancer in that setting, and the cancers are found earlier,” senior author Mark Robson, MD, said in an interview.
The model showed that mammography screening in women under 40 added no survival benefit, and led to additional false positives and benign biopsies.
“We know that MRI’s detection rate for cancers in a head-to-head comparison with mammography is extremely high, and so I’m not surprised that there was such a difference from a mammography strategy. What I was excited by is just how impactful the MRI screen was in terms of projected reduction in the risk of death. I thought that great,” said Dr. Robson, who is chief of the breast medicine service at Memorial Sloan Kettering Cancer Center, New York.
The balance of mortality reduction versus false positives and benign biopsies will need to be weighed by others. “We didn’t feel like we could make those judgments, but what we were presenting was for people who do make these kinds of policies. The reason that we said 30-35 years (for MRI initiation) is because at that point, the false positive versus life-years gained curve starts to plateau. For instance, when we look at strategies of starting MRI at 25, you we don’t get significantly more life years gained, but we do get more false positives,” Dr. Robson said.
The researchers did not conduct a former cost-benefit analysis for initiating MRI screening at age 30-35.
The study “reinforces the value of MRI for women with these variants that are really just entering the clinical consciousness, and affirms that we need to be doing that in young women to help prevent death from breast cancer. I also think that we need to look at really what mammogram is adding in young women and consider whether or not we really need it at the policy level,” he said.
The study was funded by the National Cancer Institute and the Breast Cancer Research Foundation. Dr. Robson has conducted clinical trials with AstraZeneca, Merck, and Pfizer.
Among women with ATM, CHEK2, or PALB2 pathogenic variants, annual MRI screening beginning at age 30 or 35, followed by concomitant MRI and mammography at age 40, could significantly reduce breast cancer mortality, according to a new model.
ATM, CHEK2, and PALB2 are the most common of a more recently discovered group of pathogenic variants that confer a moderate to high risk of breast cancer.
In a study published online Feb. 17, 2022, in JAMA Oncology, researchers used two simulation models and risk estimates from the Cancer Risk Estimates Related to Susceptibility Consortium to predict that MRI screening at age 35 would produce a 54.4%-57.6% reduction in breast cancer mortality, with an estimated 4,661-5,001 false positive screenings and 1,280-1,368 benign biopsies per 1,000 women. At age 30, the model predicted 55.4-59.5% reduction in risk, 5,075-5,415 false positives, and 1,439-1,528 benign biopsies. Annual mammography at age 40 alone could reduce risk by 36%-39%.
The false positives and benign biopsies represent cumulative lifetime results.
“We’ve known for a long time that mammography is less sensitive in younger women than in older women and, of course, when women have a genetic predisposition, we’re very concerned about early-onset cancer. We’ve also known that when you do MRI at the same time as mammography, you find a lot more cancers. [There are] more false positives, but there is clearly a greater yield of cancer in that setting, and the cancers are found earlier,” senior author Mark Robson, MD, said in an interview.
The model showed that mammography screening in women under 40 added no survival benefit, and led to additional false positives and benign biopsies.
“We know that MRI’s detection rate for cancers in a head-to-head comparison with mammography is extremely high, and so I’m not surprised that there was such a difference from a mammography strategy. What I was excited by is just how impactful the MRI screen was in terms of projected reduction in the risk of death. I thought that great,” said Dr. Robson, who is chief of the breast medicine service at Memorial Sloan Kettering Cancer Center, New York.
The balance of mortality reduction versus false positives and benign biopsies will need to be weighed by others. “We didn’t feel like we could make those judgments, but what we were presenting was for people who do make these kinds of policies. The reason that we said 30-35 years (for MRI initiation) is because at that point, the false positive versus life-years gained curve starts to plateau. For instance, when we look at strategies of starting MRI at 25, you we don’t get significantly more life years gained, but we do get more false positives,” Dr. Robson said.
The researchers did not conduct a former cost-benefit analysis for initiating MRI screening at age 30-35.
The study “reinforces the value of MRI for women with these variants that are really just entering the clinical consciousness, and affirms that we need to be doing that in young women to help prevent death from breast cancer. I also think that we need to look at really what mammogram is adding in young women and consider whether or not we really need it at the policy level,” he said.
The study was funded by the National Cancer Institute and the Breast Cancer Research Foundation. Dr. Robson has conducted clinical trials with AstraZeneca, Merck, and Pfizer.
Among women with ATM, CHEK2, or PALB2 pathogenic variants, annual MRI screening beginning at age 30 or 35, followed by concomitant MRI and mammography at age 40, could significantly reduce breast cancer mortality, according to a new model.
ATM, CHEK2, and PALB2 are the most common of a more recently discovered group of pathogenic variants that confer a moderate to high risk of breast cancer.
In a study published online Feb. 17, 2022, in JAMA Oncology, researchers used two simulation models and risk estimates from the Cancer Risk Estimates Related to Susceptibility Consortium to predict that MRI screening at age 35 would produce a 54.4%-57.6% reduction in breast cancer mortality, with an estimated 4,661-5,001 false positive screenings and 1,280-1,368 benign biopsies per 1,000 women. At age 30, the model predicted 55.4-59.5% reduction in risk, 5,075-5,415 false positives, and 1,439-1,528 benign biopsies. Annual mammography at age 40 alone could reduce risk by 36%-39%.
The false positives and benign biopsies represent cumulative lifetime results.
“We’ve known for a long time that mammography is less sensitive in younger women than in older women and, of course, when women have a genetic predisposition, we’re very concerned about early-onset cancer. We’ve also known that when you do MRI at the same time as mammography, you find a lot more cancers. [There are] more false positives, but there is clearly a greater yield of cancer in that setting, and the cancers are found earlier,” senior author Mark Robson, MD, said in an interview.
The model showed that mammography screening in women under 40 added no survival benefit, and led to additional false positives and benign biopsies.
“We know that MRI’s detection rate for cancers in a head-to-head comparison with mammography is extremely high, and so I’m not surprised that there was such a difference from a mammography strategy. What I was excited by is just how impactful the MRI screen was in terms of projected reduction in the risk of death. I thought that great,” said Dr. Robson, who is chief of the breast medicine service at Memorial Sloan Kettering Cancer Center, New York.
The balance of mortality reduction versus false positives and benign biopsies will need to be weighed by others. “We didn’t feel like we could make those judgments, but what we were presenting was for people who do make these kinds of policies. The reason that we said 30-35 years (for MRI initiation) is because at that point, the false positive versus life-years gained curve starts to plateau. For instance, when we look at strategies of starting MRI at 25, you we don’t get significantly more life years gained, but we do get more false positives,” Dr. Robson said.
The researchers did not conduct a former cost-benefit analysis for initiating MRI screening at age 30-35.
The study “reinforces the value of MRI for women with these variants that are really just entering the clinical consciousness, and affirms that we need to be doing that in young women to help prevent death from breast cancer. I also think that we need to look at really what mammogram is adding in young women and consider whether or not we really need it at the policy level,” he said.
The study was funded by the National Cancer Institute and the Breast Cancer Research Foundation. Dr. Robson has conducted clinical trials with AstraZeneca, Merck, and Pfizer.
FROM JAMA ONCOLOGY
Dietary fiber tied to lower dementia risk
, new research shows.
Investigators administered a dietary survey to 3,700 healthy adults at midlife and then followed them for up to 20 years. They found that participants who consumed the most fiber had approximately a 25% lower risk of developing dementia in later life.
“This study showed that people with a high intake of dietary fiber, especially soluble fiber, have a lower risk of dementia,” study investigator Kazumasa Yamagishi, MD, PhD, professor, department of public health medicine, faculty of medicine and health, Services Research and Development Center, University of Tsukuba, Japan, said in an interview.
“There are still many unknowns about the causes of dementia, and it is not appropriate to determine causality based on the results of a single cohort study. However, the results of this study can be said to be one of the findings that will lead to the prevention of dementia,” Dr. Yamagishi said.
The study was published online Feb. 6 in Nutritional Neuroscience.
Brain-gut interaction
Brain-gut interaction has recently received attention for its potential involvement in the development of dementia. “The concept of brain-gut interaction emerged from the idea that the central nervous system communicates bidirectionally with the gastrointestinal tract, suggesting that the gut microbiome may influence brain plasticity and cognitive function,” the authors wrote.
A diet high in soluble fiber attenuates neuroinflammation in mouse models. Other animal studies have suggested that insoluble fiber might also have a beneficial effect on the microbiome.
The researchers wanted to see whether dietary fiber intake – especially soluble fiber – is associated with a reduced risk of dementia. They also investigated whether there was any difference between dementia in patients with vs. without a history of stroke.
In a previous study, these same researchers reported an inverse association between eating beans, which are high in fiber, and risk of disabling dementia. In the current study, the researchers extended the analyses to dietary fiber intake of total, soluble, and insoluble fibers, as well as other fiber-containing foods, such potatoes, vegetables, and fruits. However, they distinguished potatoes from other vegetables because the composition of starch in potatoes differs.
“Dietary fiber is a nutrient found in grains, potatoes, vegetables, and fruits and is known to affect intestinal bacteria,” Dr. Yamagishi said. “Recently, some experimental studies have shown that intestinal bacteria may be involved in cognitive functions as well as diseases of the digestive tract. However, there have been no studies that have actually examined the relationship between dietary fiber intake and the subsequent risk of dementia in large numbers of general people.”
The researchers turned to participants in the Circulatory Risk in Communities Study (CIRCS), an ongoing dynamic community cohort study involving five communities in Japan. The current study focused on communities where disabling dementia surveillance is conducted.
Participants (n = 3,739) ranged in age from 40 to 64 years (mean age, 51 years) at the time they completed the 24-hour dietary recall survey, and they participated in annual health checkups from 1985 to 1999. Potential risk factors for disabling dementia were measured at the time the dietary surveys were conducted. Participants were then followed for a median of 19.7 years (1999-2020) to confirm incident, disabling dementia.
“Disabling dementia” was defined as dementia that required care under the National Long-Term Care Insurance System and was further categorized on the basis of having a history or not having a history of stroke.
The researchers divided participants into quartiles, based on the amount of total, soluble, and insoluble intake reported in their surveys. They found that men tended to consume less total fiber compared to women.
Unclear mechanism
During follow-up, 670 participants developed disabling dementia.
Total fiber intake was “inversely and linearly” associated with risk of incident dementia, the authors reported, with each successive quartile associated with a lower risk compared to the lowest quartile (P for trend = .03).
The association remained after adjustment for potential factors that might affect dementia onset, such as body mass index, systolic blood pressure, antihypertensive medication use, serum total cholesterol, cholesterol-lowering medication, and diabetes (P for trend = .05).
“The inverse association was more evident for soluble fiber intake and was confined to dementia without a history of stroke,” the authors reported. Moreover, potatoes, not vegetables or fruits, showed a similar association.
“The mechanisms are currently unknown but might involve the interactions that take place between the gut and the brain,” Dr. Yamagishi said in a release.
“One possibility is that soluble fiber regulates the composition of gut bacteria. This composition may affect neuroinflammation, which plays a role in the onset of dementia,” he suggested. “It’s also possible that dietary fiber may reduce other risk factors for dementia, such as body weight, blood pressure, lipids, and glucose levels.”
The authors noted several limitations. For example, they did not distinguish between Alzheimer’s and non-Alzheimer’s dementia. Moreover, they classified dietary habits on the basis of a single survey, and participants’ dietary patterns might have changed over the study period.
In addition, Dr. Yamagishi noted, it is “important to confirm the association in other populations.”
Balance is key
In an interview, Uma Naidoo, MD, director of nutritional and lifestyle psychiatry, Massachusetts General Hospital, and nutrition educator at Harvard Medical School, both in Boston, said the study “adds to the growing pool of evidence suggesting that a diet rich in colorful, plant-based foods can benefit our neurological and psychiatric health, especially as we age.”
Dr. Naidoo, a chef and the author of “This Is Your Brain on Food,” who was not involved in the study, continued, “In nutritional psychiatry, balance is key and therefore consuming a well-rounded diet including ample amounts of fiber – particularly from sources like steel-cut oats, beans, lentils, and numerous other fruits and vegetables – can be part of a healthy lifestyle and prevention against cognitive decline in later years.
“While the study authors admit to limitations within the study, in my opinion, eating healthier has so many mental and physical health benefits that it’s a nutritional psychiatry no-brainer,” she added.
The study was partly supported by Health and Labour Science Research Grants for Dementia from the Ministry of Health, Labour and Welfare of Japan; JSPS Kakenhi; FULLHAP; and the Osaka University International Joint Research Promotion Programme with University College London. The authors and Dr. Naidoo report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, new research shows.
Investigators administered a dietary survey to 3,700 healthy adults at midlife and then followed them for up to 20 years. They found that participants who consumed the most fiber had approximately a 25% lower risk of developing dementia in later life.
“This study showed that people with a high intake of dietary fiber, especially soluble fiber, have a lower risk of dementia,” study investigator Kazumasa Yamagishi, MD, PhD, professor, department of public health medicine, faculty of medicine and health, Services Research and Development Center, University of Tsukuba, Japan, said in an interview.
“There are still many unknowns about the causes of dementia, and it is not appropriate to determine causality based on the results of a single cohort study. However, the results of this study can be said to be one of the findings that will lead to the prevention of dementia,” Dr. Yamagishi said.
The study was published online Feb. 6 in Nutritional Neuroscience.
Brain-gut interaction
Brain-gut interaction has recently received attention for its potential involvement in the development of dementia. “The concept of brain-gut interaction emerged from the idea that the central nervous system communicates bidirectionally with the gastrointestinal tract, suggesting that the gut microbiome may influence brain plasticity and cognitive function,” the authors wrote.
A diet high in soluble fiber attenuates neuroinflammation in mouse models. Other animal studies have suggested that insoluble fiber might also have a beneficial effect on the microbiome.
The researchers wanted to see whether dietary fiber intake – especially soluble fiber – is associated with a reduced risk of dementia. They also investigated whether there was any difference between dementia in patients with vs. without a history of stroke.
In a previous study, these same researchers reported an inverse association between eating beans, which are high in fiber, and risk of disabling dementia. In the current study, the researchers extended the analyses to dietary fiber intake of total, soluble, and insoluble fibers, as well as other fiber-containing foods, such potatoes, vegetables, and fruits. However, they distinguished potatoes from other vegetables because the composition of starch in potatoes differs.
“Dietary fiber is a nutrient found in grains, potatoes, vegetables, and fruits and is known to affect intestinal bacteria,” Dr. Yamagishi said. “Recently, some experimental studies have shown that intestinal bacteria may be involved in cognitive functions as well as diseases of the digestive tract. However, there have been no studies that have actually examined the relationship between dietary fiber intake and the subsequent risk of dementia in large numbers of general people.”
The researchers turned to participants in the Circulatory Risk in Communities Study (CIRCS), an ongoing dynamic community cohort study involving five communities in Japan. The current study focused on communities where disabling dementia surveillance is conducted.
Participants (n = 3,739) ranged in age from 40 to 64 years (mean age, 51 years) at the time they completed the 24-hour dietary recall survey, and they participated in annual health checkups from 1985 to 1999. Potential risk factors for disabling dementia were measured at the time the dietary surveys were conducted. Participants were then followed for a median of 19.7 years (1999-2020) to confirm incident, disabling dementia.
“Disabling dementia” was defined as dementia that required care under the National Long-Term Care Insurance System and was further categorized on the basis of having a history or not having a history of stroke.
The researchers divided participants into quartiles, based on the amount of total, soluble, and insoluble intake reported in their surveys. They found that men tended to consume less total fiber compared to women.
Unclear mechanism
During follow-up, 670 participants developed disabling dementia.
Total fiber intake was “inversely and linearly” associated with risk of incident dementia, the authors reported, with each successive quartile associated with a lower risk compared to the lowest quartile (P for trend = .03).
The association remained after adjustment for potential factors that might affect dementia onset, such as body mass index, systolic blood pressure, antihypertensive medication use, serum total cholesterol, cholesterol-lowering medication, and diabetes (P for trend = .05).
“The inverse association was more evident for soluble fiber intake and was confined to dementia without a history of stroke,” the authors reported. Moreover, potatoes, not vegetables or fruits, showed a similar association.
“The mechanisms are currently unknown but might involve the interactions that take place between the gut and the brain,” Dr. Yamagishi said in a release.
“One possibility is that soluble fiber regulates the composition of gut bacteria. This composition may affect neuroinflammation, which plays a role in the onset of dementia,” he suggested. “It’s also possible that dietary fiber may reduce other risk factors for dementia, such as body weight, blood pressure, lipids, and glucose levels.”
The authors noted several limitations. For example, they did not distinguish between Alzheimer’s and non-Alzheimer’s dementia. Moreover, they classified dietary habits on the basis of a single survey, and participants’ dietary patterns might have changed over the study period.
In addition, Dr. Yamagishi noted, it is “important to confirm the association in other populations.”
Balance is key
In an interview, Uma Naidoo, MD, director of nutritional and lifestyle psychiatry, Massachusetts General Hospital, and nutrition educator at Harvard Medical School, both in Boston, said the study “adds to the growing pool of evidence suggesting that a diet rich in colorful, plant-based foods can benefit our neurological and psychiatric health, especially as we age.”
Dr. Naidoo, a chef and the author of “This Is Your Brain on Food,” who was not involved in the study, continued, “In nutritional psychiatry, balance is key and therefore consuming a well-rounded diet including ample amounts of fiber – particularly from sources like steel-cut oats, beans, lentils, and numerous other fruits and vegetables – can be part of a healthy lifestyle and prevention against cognitive decline in later years.
“While the study authors admit to limitations within the study, in my opinion, eating healthier has so many mental and physical health benefits that it’s a nutritional psychiatry no-brainer,” she added.
The study was partly supported by Health and Labour Science Research Grants for Dementia from the Ministry of Health, Labour and Welfare of Japan; JSPS Kakenhi; FULLHAP; and the Osaka University International Joint Research Promotion Programme with University College London. The authors and Dr. Naidoo report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, new research shows.
Investigators administered a dietary survey to 3,700 healthy adults at midlife and then followed them for up to 20 years. They found that participants who consumed the most fiber had approximately a 25% lower risk of developing dementia in later life.
“This study showed that people with a high intake of dietary fiber, especially soluble fiber, have a lower risk of dementia,” study investigator Kazumasa Yamagishi, MD, PhD, professor, department of public health medicine, faculty of medicine and health, Services Research and Development Center, University of Tsukuba, Japan, said in an interview.
“There are still many unknowns about the causes of dementia, and it is not appropriate to determine causality based on the results of a single cohort study. However, the results of this study can be said to be one of the findings that will lead to the prevention of dementia,” Dr. Yamagishi said.
The study was published online Feb. 6 in Nutritional Neuroscience.
Brain-gut interaction
Brain-gut interaction has recently received attention for its potential involvement in the development of dementia. “The concept of brain-gut interaction emerged from the idea that the central nervous system communicates bidirectionally with the gastrointestinal tract, suggesting that the gut microbiome may influence brain plasticity and cognitive function,” the authors wrote.
A diet high in soluble fiber attenuates neuroinflammation in mouse models. Other animal studies have suggested that insoluble fiber might also have a beneficial effect on the microbiome.
The researchers wanted to see whether dietary fiber intake – especially soluble fiber – is associated with a reduced risk of dementia. They also investigated whether there was any difference between dementia in patients with vs. without a history of stroke.
In a previous study, these same researchers reported an inverse association between eating beans, which are high in fiber, and risk of disabling dementia. In the current study, the researchers extended the analyses to dietary fiber intake of total, soluble, and insoluble fibers, as well as other fiber-containing foods, such potatoes, vegetables, and fruits. However, they distinguished potatoes from other vegetables because the composition of starch in potatoes differs.
“Dietary fiber is a nutrient found in grains, potatoes, vegetables, and fruits and is known to affect intestinal bacteria,” Dr. Yamagishi said. “Recently, some experimental studies have shown that intestinal bacteria may be involved in cognitive functions as well as diseases of the digestive tract. However, there have been no studies that have actually examined the relationship between dietary fiber intake and the subsequent risk of dementia in large numbers of general people.”
The researchers turned to participants in the Circulatory Risk in Communities Study (CIRCS), an ongoing dynamic community cohort study involving five communities in Japan. The current study focused on communities where disabling dementia surveillance is conducted.
Participants (n = 3,739) ranged in age from 40 to 64 years (mean age, 51 years) at the time they completed the 24-hour dietary recall survey, and they participated in annual health checkups from 1985 to 1999. Potential risk factors for disabling dementia were measured at the time the dietary surveys were conducted. Participants were then followed for a median of 19.7 years (1999-2020) to confirm incident, disabling dementia.
“Disabling dementia” was defined as dementia that required care under the National Long-Term Care Insurance System and was further categorized on the basis of having a history or not having a history of stroke.
The researchers divided participants into quartiles, based on the amount of total, soluble, and insoluble intake reported in their surveys. They found that men tended to consume less total fiber compared to women.
Unclear mechanism
During follow-up, 670 participants developed disabling dementia.
Total fiber intake was “inversely and linearly” associated with risk of incident dementia, the authors reported, with each successive quartile associated with a lower risk compared to the lowest quartile (P for trend = .03).
The association remained after adjustment for potential factors that might affect dementia onset, such as body mass index, systolic blood pressure, antihypertensive medication use, serum total cholesterol, cholesterol-lowering medication, and diabetes (P for trend = .05).
“The inverse association was more evident for soluble fiber intake and was confined to dementia without a history of stroke,” the authors reported. Moreover, potatoes, not vegetables or fruits, showed a similar association.
“The mechanisms are currently unknown but might involve the interactions that take place between the gut and the brain,” Dr. Yamagishi said in a release.
“One possibility is that soluble fiber regulates the composition of gut bacteria. This composition may affect neuroinflammation, which plays a role in the onset of dementia,” he suggested. “It’s also possible that dietary fiber may reduce other risk factors for dementia, such as body weight, blood pressure, lipids, and glucose levels.”
The authors noted several limitations. For example, they did not distinguish between Alzheimer’s and non-Alzheimer’s dementia. Moreover, they classified dietary habits on the basis of a single survey, and participants’ dietary patterns might have changed over the study period.
In addition, Dr. Yamagishi noted, it is “important to confirm the association in other populations.”
Balance is key
In an interview, Uma Naidoo, MD, director of nutritional and lifestyle psychiatry, Massachusetts General Hospital, and nutrition educator at Harvard Medical School, both in Boston, said the study “adds to the growing pool of evidence suggesting that a diet rich in colorful, plant-based foods can benefit our neurological and psychiatric health, especially as we age.”
Dr. Naidoo, a chef and the author of “This Is Your Brain on Food,” who was not involved in the study, continued, “In nutritional psychiatry, balance is key and therefore consuming a well-rounded diet including ample amounts of fiber – particularly from sources like steel-cut oats, beans, lentils, and numerous other fruits and vegetables – can be part of a healthy lifestyle and prevention against cognitive decline in later years.
“While the study authors admit to limitations within the study, in my opinion, eating healthier has so many mental and physical health benefits that it’s a nutritional psychiatry no-brainer,” she added.
The study was partly supported by Health and Labour Science Research Grants for Dementia from the Ministry of Health, Labour and Welfare of Japan; JSPS Kakenhi; FULLHAP; and the Osaka University International Joint Research Promotion Programme with University College London. The authors and Dr. Naidoo report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM NUTRITIONAL NEUROSCIENCE
Reactivation of a BCG Vaccination Scar Following the First Dose of the Moderna COVID-19 Vaccine
The COVID-19 pandemic has resulted in notable morbidity and mortality worldwide. In December 2020, the US Food and Drug Administration issued an Emergency Use Authorization for 2 messenger RNA (mRNA) vaccines—produced by Pfizer-BioNTech and Moderna—for the prevention of COVID-19. Phase 3 trials of the vaccine developed by Moderna showed 94.1% efficacy at preventing COVID-19 after 2 doses.1
Common cutaneous adverse effects of the Moderna COVID-19 Vaccine include injection-site reactions, such as pain, induration, and erythema. Less frequently reported dermatologic adverse effects include diffuse bullous rash and hypersensitivity reactions.1 We report a case of reactivation of a BCG vaccination scar after the first dose of the Moderna COVID-19 Vaccine.
Case Report
A 48-year-old Asian man who was otherwise healthy presented with erythema, induration, and mild pruritus on the deltoid muscle of the left arm, near the scar from an earlier BCG vaccine, which he received at approximately 5 years of age when living in Taiwan. The patient received the first dose of the Moderna COVID-19 Vaccine approximately 5 to 7 cm distant from the BCG vaccination scar. One to 2 days after inoculation, the patient endorsed tenderness at the site of COVID-19 vaccination but denied systemic symptoms. He had never been given a diagnosis of COVID-19. His SARS-CoV-2 antibody status was unknown.
Eight days later, the patient noticed a well-defined, erythematous, indurated plaque with mild itchiness overlying and around the BCG vaccination scar that did not involve the COVID-19 vaccination site. The following day, the redness and induration became worse (Figure).
The patient was otherwise well. Vital signs were normal; there was no lymphadenopathy. The rash resolved without treatment over the next 4 days.
Comment
The BCG vaccine is an intradermal live attenuated virus vaccine used to prevent certain forms of tuberculosis and potentially other Mycobacterium infections. Although the vaccine is not routinely administered in the United States, it is part of the vaccination schedule in most countries, administered most often to newborns and infants. Administration of the BCG vaccine commonly results in mild localized erythema, swelling, and pain at the injection site. Most inoculated patients also develop an ulcer that heals with the characteristic BCG vaccination scar.2,3
There is evidence that the BCG vaccine can enhance the innate immune system response and might decrease the rate of infection by unrelated pathogens, including viruses.4 Several epidemiologic studies have suggested that the BCG vaccine might offer some protection against COVID-19, possibly due to a resemblance of the amino acid sequences of BCG and SARS-CoV-2, which might provoke cross-reactive T cells.5,6 Further studies are underway to determine whether the BCG vaccine is truly protective against COVID-19.
BCG vaccination scar reactivation presents as redness, swelling, or ulceration at the BCG injection site months to years after inoculation. Although erythema and induration of the BCG scar are not included in the diagnostic criteria of Kawasaki disease, likely due to variable vaccine requirements in different countries, these findings are largely recognized as specific for Kawasaki disease and present in approximately half of affected patients who received the BCG vaccine.2
Heat Shock Proteins—Heat shock proteins (HSPs) are produced by cells in response to stressors. The proposed mechanism of BCG vaccination scar reactivation is a cross-reaction between human homologue HSP 63 and Mycobacterium HSP 65, leading to hyperactivity of the immune system against BCG.7 There also are reports of reactivation of a BCG vaccination scar from measles infection and influenza vaccination.2,8,9 Most prior reports of BCG vaccination scar reactivation have been in pediatric patients; our patient is an adult who received the BCG vaccine more than 40 years ago.
Mechanism of Reactivation—The mechanism of BCG vaccination scar reactivation in our patient, who received the Moderna COVID-19 Vaccine, is unclear. Possible mechanisms include (1) release of HSP mediated by the COVID-19 vaccine, leading to an immune response at the BCG vaccine scar, or (2) another immune-mediated cross-reaction between BCG and the Moderna COVID-19 Vaccine mRNA nanoparticle or encoded spike protein antigen. It has been hypothesized that the BCG vaccine might offer some protection against COVID-19; this remains uncertain and is under further investigation.10 A recent retrospective cohort study showed that a BCG vaccination booster may decrease COVID-19 infection rates in higher-risk populations.11
Conclusion
We present a case of BCG vaccine scar reactivation occurring after a dose of the Moderna COVID-19 Vaccine, a likely underreported, self-limiting, cutaneous adverse effect of this mRNA vaccine.
- Baden LR, El Sahly HM, Essink B, et al; COVE Study Group. Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine. N Engl J Med. 2020;384:403-416. doi:10.1056/NEJMoa2035389
- Muthuvelu S, Lim KS, Huang L-Y, et al. Measles infection causing bacillus Calmette-Guérin reactivation: a case report. BMC Pediatr. 2019;19:251. doi:10.1186/s12887-019-1635-z
- Fatima S, Kumari A, Das G, et al. Tuberculosis vaccine: a journey from BCG to present. Life Sci. 2020;252:117594. doi:10.1016/j.lfs.2020.117594
- O’Neill LAJ, Netea MG. BCG-induced trained immunity: can it offer protection against COVID-19? Nat Rev Immunol. 2020;20:335-337. doi:10.1038/s41577-020-0337-y
- Brooks NA, Puri A, Garg S, et al. The association of coronavirus disease-19 mortality and prior bacille Calmette-Guérin vaccination: a robust ecological analysis using unsupervised machine learning. Sci Rep. 2021;11:774. doi:10.1038/s41598-020-80787-z
- Tomita Y, Sato R, Ikeda T, et al. BCG vaccine may generate cross-reactive T-cells against SARS-CoV-2: in silico analyses and a hypothesis. Vaccine. 2020;38:6352-6356. doi:10.1016/j.vaccine.2020.08.045
- Lim KYY, Chua MC, Tan NWH, et al. Reactivation of BCG inoculation site in a child with febrile exanthema of 3 days duration: an early indicator of incomplete Kawasaki disease. BMJ Case Rep. 2020;13:E239648. doi:10.1136/bcr-2020-239648
- Kondo M, Goto H, Yamamoto S. First case of redness and erosion at bacillus Calmette-Guérin inoculation site after vaccination against influenza. J Dermatol. 2016;43:1229-1231. doi:10.1111/1346-8138.13365
- Chavarri-Guerra Y, Soto-Pérez-de-Celis E. Erythema at the bacillus Calmette-Guerin scar after influenza vaccination. Rev Soc Bras Med Trop. 2019;53:E20190390. doi:10.1590/0037-8682-0390-2019
- Fu W, Ho P-C, Liu C-L, et al. Reconcile the debate over protective effects of BCG vaccine against COVID-19. Sci Rep. 2021;11:8356. doi:10.1038/s41598-021-87731-9
- Amirlak L, Haddad R, Hardy JD, et al. Effectiveness of booster BCG vaccination in preventing COVID-19 infection. Hum Vaccin Immunother. 2021;17:3913-3915. doi:10.1080/21645515.2021.1956228
The COVID-19 pandemic has resulted in notable morbidity and mortality worldwide. In December 2020, the US Food and Drug Administration issued an Emergency Use Authorization for 2 messenger RNA (mRNA) vaccines—produced by Pfizer-BioNTech and Moderna—for the prevention of COVID-19. Phase 3 trials of the vaccine developed by Moderna showed 94.1% efficacy at preventing COVID-19 after 2 doses.1
Common cutaneous adverse effects of the Moderna COVID-19 Vaccine include injection-site reactions, such as pain, induration, and erythema. Less frequently reported dermatologic adverse effects include diffuse bullous rash and hypersensitivity reactions.1 We report a case of reactivation of a BCG vaccination scar after the first dose of the Moderna COVID-19 Vaccine.
Case Report
A 48-year-old Asian man who was otherwise healthy presented with erythema, induration, and mild pruritus on the deltoid muscle of the left arm, near the scar from an earlier BCG vaccine, which he received at approximately 5 years of age when living in Taiwan. The patient received the first dose of the Moderna COVID-19 Vaccine approximately 5 to 7 cm distant from the BCG vaccination scar. One to 2 days after inoculation, the patient endorsed tenderness at the site of COVID-19 vaccination but denied systemic symptoms. He had never been given a diagnosis of COVID-19. His SARS-CoV-2 antibody status was unknown.
Eight days later, the patient noticed a well-defined, erythematous, indurated plaque with mild itchiness overlying and around the BCG vaccination scar that did not involve the COVID-19 vaccination site. The following day, the redness and induration became worse (Figure).
The patient was otherwise well. Vital signs were normal; there was no lymphadenopathy. The rash resolved without treatment over the next 4 days.
Comment
The BCG vaccine is an intradermal live attenuated virus vaccine used to prevent certain forms of tuberculosis and potentially other Mycobacterium infections. Although the vaccine is not routinely administered in the United States, it is part of the vaccination schedule in most countries, administered most often to newborns and infants. Administration of the BCG vaccine commonly results in mild localized erythema, swelling, and pain at the injection site. Most inoculated patients also develop an ulcer that heals with the characteristic BCG vaccination scar.2,3
There is evidence that the BCG vaccine can enhance the innate immune system response and might decrease the rate of infection by unrelated pathogens, including viruses.4 Several epidemiologic studies have suggested that the BCG vaccine might offer some protection against COVID-19, possibly due to a resemblance of the amino acid sequences of BCG and SARS-CoV-2, which might provoke cross-reactive T cells.5,6 Further studies are underway to determine whether the BCG vaccine is truly protective against COVID-19.
BCG vaccination scar reactivation presents as redness, swelling, or ulceration at the BCG injection site months to years after inoculation. Although erythema and induration of the BCG scar are not included in the diagnostic criteria of Kawasaki disease, likely due to variable vaccine requirements in different countries, these findings are largely recognized as specific for Kawasaki disease and present in approximately half of affected patients who received the BCG vaccine.2
Heat Shock Proteins—Heat shock proteins (HSPs) are produced by cells in response to stressors. The proposed mechanism of BCG vaccination scar reactivation is a cross-reaction between human homologue HSP 63 and Mycobacterium HSP 65, leading to hyperactivity of the immune system against BCG.7 There also are reports of reactivation of a BCG vaccination scar from measles infection and influenza vaccination.2,8,9 Most prior reports of BCG vaccination scar reactivation have been in pediatric patients; our patient is an adult who received the BCG vaccine more than 40 years ago.
Mechanism of Reactivation—The mechanism of BCG vaccination scar reactivation in our patient, who received the Moderna COVID-19 Vaccine, is unclear. Possible mechanisms include (1) release of HSP mediated by the COVID-19 vaccine, leading to an immune response at the BCG vaccine scar, or (2) another immune-mediated cross-reaction between BCG and the Moderna COVID-19 Vaccine mRNA nanoparticle or encoded spike protein antigen. It has been hypothesized that the BCG vaccine might offer some protection against COVID-19; this remains uncertain and is under further investigation.10 A recent retrospective cohort study showed that a BCG vaccination booster may decrease COVID-19 infection rates in higher-risk populations.11
Conclusion
We present a case of BCG vaccine scar reactivation occurring after a dose of the Moderna COVID-19 Vaccine, a likely underreported, self-limiting, cutaneous adverse effect of this mRNA vaccine.
The COVID-19 pandemic has resulted in notable morbidity and mortality worldwide. In December 2020, the US Food and Drug Administration issued an Emergency Use Authorization for 2 messenger RNA (mRNA) vaccines—produced by Pfizer-BioNTech and Moderna—for the prevention of COVID-19. Phase 3 trials of the vaccine developed by Moderna showed 94.1% efficacy at preventing COVID-19 after 2 doses.1
Common cutaneous adverse effects of the Moderna COVID-19 Vaccine include injection-site reactions, such as pain, induration, and erythema. Less frequently reported dermatologic adverse effects include diffuse bullous rash and hypersensitivity reactions.1 We report a case of reactivation of a BCG vaccination scar after the first dose of the Moderna COVID-19 Vaccine.
Case Report
A 48-year-old Asian man who was otherwise healthy presented with erythema, induration, and mild pruritus on the deltoid muscle of the left arm, near the scar from an earlier BCG vaccine, which he received at approximately 5 years of age when living in Taiwan. The patient received the first dose of the Moderna COVID-19 Vaccine approximately 5 to 7 cm distant from the BCG vaccination scar. One to 2 days after inoculation, the patient endorsed tenderness at the site of COVID-19 vaccination but denied systemic symptoms. He had never been given a diagnosis of COVID-19. His SARS-CoV-2 antibody status was unknown.
Eight days later, the patient noticed a well-defined, erythematous, indurated plaque with mild itchiness overlying and around the BCG vaccination scar that did not involve the COVID-19 vaccination site. The following day, the redness and induration became worse (Figure).
The patient was otherwise well. Vital signs were normal; there was no lymphadenopathy. The rash resolved without treatment over the next 4 days.
Comment
The BCG vaccine is an intradermal live attenuated virus vaccine used to prevent certain forms of tuberculosis and potentially other Mycobacterium infections. Although the vaccine is not routinely administered in the United States, it is part of the vaccination schedule in most countries, administered most often to newborns and infants. Administration of the BCG vaccine commonly results in mild localized erythema, swelling, and pain at the injection site. Most inoculated patients also develop an ulcer that heals with the characteristic BCG vaccination scar.2,3
There is evidence that the BCG vaccine can enhance the innate immune system response and might decrease the rate of infection by unrelated pathogens, including viruses.4 Several epidemiologic studies have suggested that the BCG vaccine might offer some protection against COVID-19, possibly due to a resemblance of the amino acid sequences of BCG and SARS-CoV-2, which might provoke cross-reactive T cells.5,6 Further studies are underway to determine whether the BCG vaccine is truly protective against COVID-19.
BCG vaccination scar reactivation presents as redness, swelling, or ulceration at the BCG injection site months to years after inoculation. Although erythema and induration of the BCG scar are not included in the diagnostic criteria of Kawasaki disease, likely due to variable vaccine requirements in different countries, these findings are largely recognized as specific for Kawasaki disease and present in approximately half of affected patients who received the BCG vaccine.2
Heat Shock Proteins—Heat shock proteins (HSPs) are produced by cells in response to stressors. The proposed mechanism of BCG vaccination scar reactivation is a cross-reaction between human homologue HSP 63 and Mycobacterium HSP 65, leading to hyperactivity of the immune system against BCG.7 There also are reports of reactivation of a BCG vaccination scar from measles infection and influenza vaccination.2,8,9 Most prior reports of BCG vaccination scar reactivation have been in pediatric patients; our patient is an adult who received the BCG vaccine more than 40 years ago.
Mechanism of Reactivation—The mechanism of BCG vaccination scar reactivation in our patient, who received the Moderna COVID-19 Vaccine, is unclear. Possible mechanisms include (1) release of HSP mediated by the COVID-19 vaccine, leading to an immune response at the BCG vaccine scar, or (2) another immune-mediated cross-reaction between BCG and the Moderna COVID-19 Vaccine mRNA nanoparticle or encoded spike protein antigen. It has been hypothesized that the BCG vaccine might offer some protection against COVID-19; this remains uncertain and is under further investigation.10 A recent retrospective cohort study showed that a BCG vaccination booster may decrease COVID-19 infection rates in higher-risk populations.11
Conclusion
We present a case of BCG vaccine scar reactivation occurring after a dose of the Moderna COVID-19 Vaccine, a likely underreported, self-limiting, cutaneous adverse effect of this mRNA vaccine.
- Baden LR, El Sahly HM, Essink B, et al; COVE Study Group. Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine. N Engl J Med. 2020;384:403-416. doi:10.1056/NEJMoa2035389
- Muthuvelu S, Lim KS, Huang L-Y, et al. Measles infection causing bacillus Calmette-Guérin reactivation: a case report. BMC Pediatr. 2019;19:251. doi:10.1186/s12887-019-1635-z
- Fatima S, Kumari A, Das G, et al. Tuberculosis vaccine: a journey from BCG to present. Life Sci. 2020;252:117594. doi:10.1016/j.lfs.2020.117594
- O’Neill LAJ, Netea MG. BCG-induced trained immunity: can it offer protection against COVID-19? Nat Rev Immunol. 2020;20:335-337. doi:10.1038/s41577-020-0337-y
- Brooks NA, Puri A, Garg S, et al. The association of coronavirus disease-19 mortality and prior bacille Calmette-Guérin vaccination: a robust ecological analysis using unsupervised machine learning. Sci Rep. 2021;11:774. doi:10.1038/s41598-020-80787-z
- Tomita Y, Sato R, Ikeda T, et al. BCG vaccine may generate cross-reactive T-cells against SARS-CoV-2: in silico analyses and a hypothesis. Vaccine. 2020;38:6352-6356. doi:10.1016/j.vaccine.2020.08.045
- Lim KYY, Chua MC, Tan NWH, et al. Reactivation of BCG inoculation site in a child with febrile exanthema of 3 days duration: an early indicator of incomplete Kawasaki disease. BMJ Case Rep. 2020;13:E239648. doi:10.1136/bcr-2020-239648
- Kondo M, Goto H, Yamamoto S. First case of redness and erosion at bacillus Calmette-Guérin inoculation site after vaccination against influenza. J Dermatol. 2016;43:1229-1231. doi:10.1111/1346-8138.13365
- Chavarri-Guerra Y, Soto-Pérez-de-Celis E. Erythema at the bacillus Calmette-Guerin scar after influenza vaccination. Rev Soc Bras Med Trop. 2019;53:E20190390. doi:10.1590/0037-8682-0390-2019
- Fu W, Ho P-C, Liu C-L, et al. Reconcile the debate over protective effects of BCG vaccine against COVID-19. Sci Rep. 2021;11:8356. doi:10.1038/s41598-021-87731-9
- Amirlak L, Haddad R, Hardy JD, et al. Effectiveness of booster BCG vaccination in preventing COVID-19 infection. Hum Vaccin Immunother. 2021;17:3913-3915. doi:10.1080/21645515.2021.1956228
- Baden LR, El Sahly HM, Essink B, et al; COVE Study Group. Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine. N Engl J Med. 2020;384:403-416. doi:10.1056/NEJMoa2035389
- Muthuvelu S, Lim KS, Huang L-Y, et al. Measles infection causing bacillus Calmette-Guérin reactivation: a case report. BMC Pediatr. 2019;19:251. doi:10.1186/s12887-019-1635-z
- Fatima S, Kumari A, Das G, et al. Tuberculosis vaccine: a journey from BCG to present. Life Sci. 2020;252:117594. doi:10.1016/j.lfs.2020.117594
- O’Neill LAJ, Netea MG. BCG-induced trained immunity: can it offer protection against COVID-19? Nat Rev Immunol. 2020;20:335-337. doi:10.1038/s41577-020-0337-y
- Brooks NA, Puri A, Garg S, et al. The association of coronavirus disease-19 mortality and prior bacille Calmette-Guérin vaccination: a robust ecological analysis using unsupervised machine learning. Sci Rep. 2021;11:774. doi:10.1038/s41598-020-80787-z
- Tomita Y, Sato R, Ikeda T, et al. BCG vaccine may generate cross-reactive T-cells against SARS-CoV-2: in silico analyses and a hypothesis. Vaccine. 2020;38:6352-6356. doi:10.1016/j.vaccine.2020.08.045
- Lim KYY, Chua MC, Tan NWH, et al. Reactivation of BCG inoculation site in a child with febrile exanthema of 3 days duration: an early indicator of incomplete Kawasaki disease. BMJ Case Rep. 2020;13:E239648. doi:10.1136/bcr-2020-239648
- Kondo M, Goto H, Yamamoto S. First case of redness and erosion at bacillus Calmette-Guérin inoculation site after vaccination against influenza. J Dermatol. 2016;43:1229-1231. doi:10.1111/1346-8138.13365
- Chavarri-Guerra Y, Soto-Pérez-de-Celis E. Erythema at the bacillus Calmette-Guerin scar after influenza vaccination. Rev Soc Bras Med Trop. 2019;53:E20190390. doi:10.1590/0037-8682-0390-2019
- Fu W, Ho P-C, Liu C-L, et al. Reconcile the debate over protective effects of BCG vaccine against COVID-19. Sci Rep. 2021;11:8356. doi:10.1038/s41598-021-87731-9
- Amirlak L, Haddad R, Hardy JD, et al. Effectiveness of booster BCG vaccination in preventing COVID-19 infection. Hum Vaccin Immunother. 2021;17:3913-3915. doi:10.1080/21645515.2021.1956228
Practice Points
- BCG vaccination scar reactivation is a potential benign, self-limited reaction in patients who receive the Moderna COVID-19 Vaccine.
- Symptoms of BCG vaccination scar reactivation, which is seen more commonly in children with Kawasaki disease, include redness, swelling, and ulceration.
15th Report on Carcinogens Adds to Its List
From environmental tobacco smoke to ultraviolet (UV) radiation, diesel exhaust particulates, lead, and now, chronic infection with Helicobacter pylori (H pylori)—the Report on Carcinogens has regularly updated the list of substances known or “reasonably anticipated” to cause cancer.
The 15th report, which is prepared by the National Toxicology Program (NTP) for the Department of Health and Human Services, has 8 new entries, bringing the number of human carcinogens (eg, metals, pesticides, and drugs) on the list to 256. (The first report, released in 1980, listed 26.) In addition to H pylori infection, this edition adds the flame-retardant chemical antimony trioxide, and 6 haloacetic acids found as water disinfection byproducts.
In 1971, then President Nixon declared “war on cancer” (the second leading cause of death in the US) and signed the National Cancer Act. In 1978, Congress ordered the Report on Carcinogens, to educate the public and health professionals on potential environmental carcinogenic hazards.
Perhaps disheartening to know that even with 256 entries, the list probably understates the number of carcinogens humans and other creatures are exposed to. But things can change with time. Each list goes through a rigorous round of reviews. Sometimes substances are “delisted” after, for instance, litigation or new research. Saccharin, for example, was removed from the ninth edition. It was listed as “reasonably anticipated” in 1981, based on “sufficient evidence of carcinogenicity in experimental animals.” It was removed, however, after extensive review of decades of saccharin use determined that the data were not sufficient to meet current criteria. Further research had revealed, also, that the observed bladder tumors in rats arose from a mechanism not relevant to humans.
Other entries, such as the controversial listing of the cancer drug tamoxifen, walk a fine line between risk and benefit. Tamoxifen, first listed in the ninth report (and still in the 15th report), was included because studies revealed that it could increase the risk of uterine cancer in women. But there also was conclusive evidence that it may prevent or delay breast cancer in women who are at high risk.
Ultimately, the report’s authors make it clear that it is for informative value and guidance, not necessarily a dictate. As one report put it: “Personal decisions concerning voluntary exposures to carcinogenic agents need to be based on additional information that is beyond the scope” of the report.
“As the identification of carcinogens is a key step in cancer prevention,” said Rick Woychik, PhD, director of the National Institute of Environmental Health Sciences and NTP, “publication of the report represents an important government activity towards improving public health.”
From environmental tobacco smoke to ultraviolet (UV) radiation, diesel exhaust particulates, lead, and now, chronic infection with Helicobacter pylori (H pylori)—the Report on Carcinogens has regularly updated the list of substances known or “reasonably anticipated” to cause cancer.
The 15th report, which is prepared by the National Toxicology Program (NTP) for the Department of Health and Human Services, has 8 new entries, bringing the number of human carcinogens (eg, metals, pesticides, and drugs) on the list to 256. (The first report, released in 1980, listed 26.) In addition to H pylori infection, this edition adds the flame-retardant chemical antimony trioxide, and 6 haloacetic acids found as water disinfection byproducts.
In 1971, then President Nixon declared “war on cancer” (the second leading cause of death in the US) and signed the National Cancer Act. In 1978, Congress ordered the Report on Carcinogens, to educate the public and health professionals on potential environmental carcinogenic hazards.
Perhaps disheartening to know that even with 256 entries, the list probably understates the number of carcinogens humans and other creatures are exposed to. But things can change with time. Each list goes through a rigorous round of reviews. Sometimes substances are “delisted” after, for instance, litigation or new research. Saccharin, for example, was removed from the ninth edition. It was listed as “reasonably anticipated” in 1981, based on “sufficient evidence of carcinogenicity in experimental animals.” It was removed, however, after extensive review of decades of saccharin use determined that the data were not sufficient to meet current criteria. Further research had revealed, also, that the observed bladder tumors in rats arose from a mechanism not relevant to humans.
Other entries, such as the controversial listing of the cancer drug tamoxifen, walk a fine line between risk and benefit. Tamoxifen, first listed in the ninth report (and still in the 15th report), was included because studies revealed that it could increase the risk of uterine cancer in women. But there also was conclusive evidence that it may prevent or delay breast cancer in women who are at high risk.
Ultimately, the report’s authors make it clear that it is for informative value and guidance, not necessarily a dictate. As one report put it: “Personal decisions concerning voluntary exposures to carcinogenic agents need to be based on additional information that is beyond the scope” of the report.
“As the identification of carcinogens is a key step in cancer prevention,” said Rick Woychik, PhD, director of the National Institute of Environmental Health Sciences and NTP, “publication of the report represents an important government activity towards improving public health.”
From environmental tobacco smoke to ultraviolet (UV) radiation, diesel exhaust particulates, lead, and now, chronic infection with Helicobacter pylori (H pylori)—the Report on Carcinogens has regularly updated the list of substances known or “reasonably anticipated” to cause cancer.
The 15th report, which is prepared by the National Toxicology Program (NTP) for the Department of Health and Human Services, has 8 new entries, bringing the number of human carcinogens (eg, metals, pesticides, and drugs) on the list to 256. (The first report, released in 1980, listed 26.) In addition to H pylori infection, this edition adds the flame-retardant chemical antimony trioxide, and 6 haloacetic acids found as water disinfection byproducts.
In 1971, then President Nixon declared “war on cancer” (the second leading cause of death in the US) and signed the National Cancer Act. In 1978, Congress ordered the Report on Carcinogens, to educate the public and health professionals on potential environmental carcinogenic hazards.
Perhaps disheartening to know that even with 256 entries, the list probably understates the number of carcinogens humans and other creatures are exposed to. But things can change with time. Each list goes through a rigorous round of reviews. Sometimes substances are “delisted” after, for instance, litigation or new research. Saccharin, for example, was removed from the ninth edition. It was listed as “reasonably anticipated” in 1981, based on “sufficient evidence of carcinogenicity in experimental animals.” It was removed, however, after extensive review of decades of saccharin use determined that the data were not sufficient to meet current criteria. Further research had revealed, also, that the observed bladder tumors in rats arose from a mechanism not relevant to humans.
Other entries, such as the controversial listing of the cancer drug tamoxifen, walk a fine line between risk and benefit. Tamoxifen, first listed in the ninth report (and still in the 15th report), was included because studies revealed that it could increase the risk of uterine cancer in women. But there also was conclusive evidence that it may prevent or delay breast cancer in women who are at high risk.
Ultimately, the report’s authors make it clear that it is for informative value and guidance, not necessarily a dictate. As one report put it: “Personal decisions concerning voluntary exposures to carcinogenic agents need to be based on additional information that is beyond the scope” of the report.
“As the identification of carcinogens is a key step in cancer prevention,” said Rick Woychik, PhD, director of the National Institute of Environmental Health Sciences and NTP, “publication of the report represents an important government activity towards improving public health.”
Long COVID patients may develop nerve damage: Study
according to a new study published in the journal Neurology: Neuroimmunology & Neuroinflammation (doi: 10.1212/NXI.0000000000001146).
The nerve damage, which has been seen even among mild coronavirus cases, appears to be caused by immunity problems triggered by infection.
“This is one of the early papers looking into causes of long COVID, which will steadily increase in importance as acute COVID wanes,” Anne Louise Oaklander, MD, the lead study author and a neurologist at Massachusetts General Hospital, Boston, said in a statement.
“Our findings suggest that some long COVID patients had damage to their peripheral nerve fibers and that damage to the small-fiber type of nerve cell may be prominent,” she said.
The research team analyzed data from 17 COVID-19 survivors with lingering symptoms who had no history or risks of neuropathy, or nerve damage or disease. The patients were from 10 states and territories, and all but one had mild infections.
They found that 10 patients – or 59% – had at least one test that confirmed neuropathy. Two patients had rare neuropathies that affected muscle nerves, and 10 were diagnosed with small-fiber neuropathy, which is a cause of chronic pain. Common symptoms included fatigue, weakness, changes in their senses, and pain in their hands and feet.
For treatment, 11 patients were given immunotherapies such as corticosteroids or intravenous immunoglobulins, and the five patients who received repeated IgG treatments appeared to benefit. Over time, 52% of patients improved, though none had all of their symptoms go away.
“Research from our team and others is clarifying what the different types of post-COVID neuropathy are and how best to diagnose and treat them,” she said. “Most long COVID neuropathies described so far appear to reflect immune responses to the virus that went off course.”
Dr. Oaklander noted that researchers haven’t been able to do clinical trials to evaluate specific post-COVID neuropathy treatments. But some existing treatments may help.
“Some patients seem to improve from standard treatments for other immune-related neuropathies,” she said.
A version of this article first appeared on WebMD.com.
according to a new study published in the journal Neurology: Neuroimmunology & Neuroinflammation (doi: 10.1212/NXI.0000000000001146).
The nerve damage, which has been seen even among mild coronavirus cases, appears to be caused by immunity problems triggered by infection.
“This is one of the early papers looking into causes of long COVID, which will steadily increase in importance as acute COVID wanes,” Anne Louise Oaklander, MD, the lead study author and a neurologist at Massachusetts General Hospital, Boston, said in a statement.
“Our findings suggest that some long COVID patients had damage to their peripheral nerve fibers and that damage to the small-fiber type of nerve cell may be prominent,” she said.
The research team analyzed data from 17 COVID-19 survivors with lingering symptoms who had no history or risks of neuropathy, or nerve damage or disease. The patients were from 10 states and territories, and all but one had mild infections.
They found that 10 patients – or 59% – had at least one test that confirmed neuropathy. Two patients had rare neuropathies that affected muscle nerves, and 10 were diagnosed with small-fiber neuropathy, which is a cause of chronic pain. Common symptoms included fatigue, weakness, changes in their senses, and pain in their hands and feet.
For treatment, 11 patients were given immunotherapies such as corticosteroids or intravenous immunoglobulins, and the five patients who received repeated IgG treatments appeared to benefit. Over time, 52% of patients improved, though none had all of their symptoms go away.
“Research from our team and others is clarifying what the different types of post-COVID neuropathy are and how best to diagnose and treat them,” she said. “Most long COVID neuropathies described so far appear to reflect immune responses to the virus that went off course.”
Dr. Oaklander noted that researchers haven’t been able to do clinical trials to evaluate specific post-COVID neuropathy treatments. But some existing treatments may help.
“Some patients seem to improve from standard treatments for other immune-related neuropathies,” she said.
A version of this article first appeared on WebMD.com.
according to a new study published in the journal Neurology: Neuroimmunology & Neuroinflammation (doi: 10.1212/NXI.0000000000001146).
The nerve damage, which has been seen even among mild coronavirus cases, appears to be caused by immunity problems triggered by infection.
“This is one of the early papers looking into causes of long COVID, which will steadily increase in importance as acute COVID wanes,” Anne Louise Oaklander, MD, the lead study author and a neurologist at Massachusetts General Hospital, Boston, said in a statement.
“Our findings suggest that some long COVID patients had damage to their peripheral nerve fibers and that damage to the small-fiber type of nerve cell may be prominent,” she said.
The research team analyzed data from 17 COVID-19 survivors with lingering symptoms who had no history or risks of neuropathy, or nerve damage or disease. The patients were from 10 states and territories, and all but one had mild infections.
They found that 10 patients – or 59% – had at least one test that confirmed neuropathy. Two patients had rare neuropathies that affected muscle nerves, and 10 were diagnosed with small-fiber neuropathy, which is a cause of chronic pain. Common symptoms included fatigue, weakness, changes in their senses, and pain in their hands and feet.
For treatment, 11 patients were given immunotherapies such as corticosteroids or intravenous immunoglobulins, and the five patients who received repeated IgG treatments appeared to benefit. Over time, 52% of patients improved, though none had all of their symptoms go away.
“Research from our team and others is clarifying what the different types of post-COVID neuropathy are and how best to diagnose and treat them,” she said. “Most long COVID neuropathies described so far appear to reflect immune responses to the virus that went off course.”
Dr. Oaklander noted that researchers haven’t been able to do clinical trials to evaluate specific post-COVID neuropathy treatments. But some existing treatments may help.
“Some patients seem to improve from standard treatments for other immune-related neuropathies,” she said.
A version of this article first appeared on WebMD.com.
FROM NEUROLOGY: NEUROIMMUNOLOGY & NEUROINFLAMMATION
Aspirin fails to inhibit breast cancer recurrence
Aspirin use failed to reduce recurrence rates among women with breast cancer in a phase 3, randomized, controlled trial that was halted following a planned futility analysis. The aspirin group actually had greater risk of recurrence, though the result did not reach statistical significance. Aspirin has proven effective in reducing recurrence rates in colon cancer.
Despite the disappointment of the results, Wendy Chen, MD, of Dana-Farber Cancer Institute, Boston, emphasized the value of the study. “Negative studies provide important data. You don’t want people doing something that’s not going to be helping them. There have been a lot of negative studies that have still provided important clinical information,” said Dr. Chen, who presented the results of the study at the ASCO Plenary Series.
Even study participants took the news with equanimity. “What has really been gratifying is that the patients, when we did tell them about the results, all of them [said] ‘I’m really glad I participated in the study anyway. I think it was an important question.’ And this is why we do studies. You don’t do studies because every single one of them is going to show a benefit. We do studies knowing that some of them are going to show no benefit,” said Dr. Chen.
The study included 3,021 women under age 70, recruited from 338 sites between 2017 and 2020, who were randomized to 300 mg daily aspirin or placebo. The median follow-up was 24.0 months. Dropout was high, with only 56% of patients still taking aspirin or placebo at the end of the study. The percentage was nearly identical in both arms. That low treatment rate could potentially explain the lack of an apparent effect, but Dr. Chen noted that the incidence of recurrence was actually higher in the aspirin group (hazard ratio, 1.25), though the result was not statistically significant (P = .1258). “The amount that it would need to flip in the second half [of the study] would really be of such a large magnitude to flip it. That biologically would not be plausible,” Dr. Chen said.
Previous epidemiological and even post hoc analyses of other clinical trials had suggested that aspirin might be effective at reducing recurrence in breast cancer, including data from 39,876 participants in the Women’s Health Study suggesting a reduction in risk of metastatic adenocarcinoma, but this isn’t the first time such evidence has led researchers and physicians astray. Dr. Chen pointed to hormone replacement therapy, which was prescribed for the prevention of breast cancer recurrence on the basis of similar evidence, but was shown to be harmful in a randomized, controlled trial.
“It was a very similar situation. Fortunately, the aspirin in this population was not causing harm, but it is possible that there are a lot of people who are just taking aspirin on their own, and they may be over 70, or they may have have other risk factors for adverse events that are different from our population,” Dr. Chen said.
The study was funded by the U.S. Department of Defense and the National Cancer Institute. Bayer provided aspirin and placebo for the study.
Aspirin use failed to reduce recurrence rates among women with breast cancer in a phase 3, randomized, controlled trial that was halted following a planned futility analysis. The aspirin group actually had greater risk of recurrence, though the result did not reach statistical significance. Aspirin has proven effective in reducing recurrence rates in colon cancer.
Despite the disappointment of the results, Wendy Chen, MD, of Dana-Farber Cancer Institute, Boston, emphasized the value of the study. “Negative studies provide important data. You don’t want people doing something that’s not going to be helping them. There have been a lot of negative studies that have still provided important clinical information,” said Dr. Chen, who presented the results of the study at the ASCO Plenary Series.
Even study participants took the news with equanimity. “What has really been gratifying is that the patients, when we did tell them about the results, all of them [said] ‘I’m really glad I participated in the study anyway. I think it was an important question.’ And this is why we do studies. You don’t do studies because every single one of them is going to show a benefit. We do studies knowing that some of them are going to show no benefit,” said Dr. Chen.
The study included 3,021 women under age 70, recruited from 338 sites between 2017 and 2020, who were randomized to 300 mg daily aspirin or placebo. The median follow-up was 24.0 months. Dropout was high, with only 56% of patients still taking aspirin or placebo at the end of the study. The percentage was nearly identical in both arms. That low treatment rate could potentially explain the lack of an apparent effect, but Dr. Chen noted that the incidence of recurrence was actually higher in the aspirin group (hazard ratio, 1.25), though the result was not statistically significant (P = .1258). “The amount that it would need to flip in the second half [of the study] would really be of such a large magnitude to flip it. That biologically would not be plausible,” Dr. Chen said.
Previous epidemiological and even post hoc analyses of other clinical trials had suggested that aspirin might be effective at reducing recurrence in breast cancer, including data from 39,876 participants in the Women’s Health Study suggesting a reduction in risk of metastatic adenocarcinoma, but this isn’t the first time such evidence has led researchers and physicians astray. Dr. Chen pointed to hormone replacement therapy, which was prescribed for the prevention of breast cancer recurrence on the basis of similar evidence, but was shown to be harmful in a randomized, controlled trial.
“It was a very similar situation. Fortunately, the aspirin in this population was not causing harm, but it is possible that there are a lot of people who are just taking aspirin on their own, and they may be over 70, or they may have have other risk factors for adverse events that are different from our population,” Dr. Chen said.
The study was funded by the U.S. Department of Defense and the National Cancer Institute. Bayer provided aspirin and placebo for the study.
Aspirin use failed to reduce recurrence rates among women with breast cancer in a phase 3, randomized, controlled trial that was halted following a planned futility analysis. The aspirin group actually had greater risk of recurrence, though the result did not reach statistical significance. Aspirin has proven effective in reducing recurrence rates in colon cancer.
Despite the disappointment of the results, Wendy Chen, MD, of Dana-Farber Cancer Institute, Boston, emphasized the value of the study. “Negative studies provide important data. You don’t want people doing something that’s not going to be helping them. There have been a lot of negative studies that have still provided important clinical information,” said Dr. Chen, who presented the results of the study at the ASCO Plenary Series.
Even study participants took the news with equanimity. “What has really been gratifying is that the patients, when we did tell them about the results, all of them [said] ‘I’m really glad I participated in the study anyway. I think it was an important question.’ And this is why we do studies. You don’t do studies because every single one of them is going to show a benefit. We do studies knowing that some of them are going to show no benefit,” said Dr. Chen.
The study included 3,021 women under age 70, recruited from 338 sites between 2017 and 2020, who were randomized to 300 mg daily aspirin or placebo. The median follow-up was 24.0 months. Dropout was high, with only 56% of patients still taking aspirin or placebo at the end of the study. The percentage was nearly identical in both arms. That low treatment rate could potentially explain the lack of an apparent effect, but Dr. Chen noted that the incidence of recurrence was actually higher in the aspirin group (hazard ratio, 1.25), though the result was not statistically significant (P = .1258). “The amount that it would need to flip in the second half [of the study] would really be of such a large magnitude to flip it. That biologically would not be plausible,” Dr. Chen said.
Previous epidemiological and even post hoc analyses of other clinical trials had suggested that aspirin might be effective at reducing recurrence in breast cancer, including data from 39,876 participants in the Women’s Health Study suggesting a reduction in risk of metastatic adenocarcinoma, but this isn’t the first time such evidence has led researchers and physicians astray. Dr. Chen pointed to hormone replacement therapy, which was prescribed for the prevention of breast cancer recurrence on the basis of similar evidence, but was shown to be harmful in a randomized, controlled trial.
“It was a very similar situation. Fortunately, the aspirin in this population was not causing harm, but it is possible that there are a lot of people who are just taking aspirin on their own, and they may be over 70, or they may have have other risk factors for adverse events that are different from our population,” Dr. Chen said.
The study was funded by the U.S. Department of Defense and the National Cancer Institute. Bayer provided aspirin and placebo for the study.
FROM ASCO PLENARY SERIES
Oncology care model reduces cost of supportive care meds
The Oncology Care Model (OCM), launched by the Centers for Medicare & Medicaid Services (CMS) with the goal of reducing spending for Medicare beneficiaries, was “associated with meaningful changes in the use of supportive care medications during chemotherapy treatment episodes,” according to new findings.
The OCM led to a statistically significant reduction in the use of denosumab – a pricier bone-modifying drug – by patients with bone metastases without changing the overall use of bone-modifying medications. The OCM also prompted more rapid adoption of a less expensive white blood cell growth factor agent – the biosimilar filgrastim – and more selective use of costly antiemetics as primary prophylaxis for chemotherapy-induced nausea.
study author Gabriel A. Brooks, MD, MPH, of the Dartmouth Institute for Health Policy and Clinical Practice, Geisel School of Medicine, Lebanon, N.H., and colleagues write.
The study was published online Feb. 25 in the Journal of Clinical Oncology.
Since the OCM was launched in 2016, several studies have evaluated whether the alternative payment model reached its goal of reducing spending while improving or maintaining the quality of cancer care.
The results have been decidedly mixed.
As previously reported by this news organization, one study found that after 4 years, the OCM led to a $155 million net loss to Medicare. During that time, physician participation in the program also declined, with the number of practices dropping almost 30% between 2016 and 2020.
Other studies, however, have highlighted more positive results.
One large community practice reported saving Medicare $3 million over the course of 1 year. Another analysis found that among community practices that adopted the OCM, in the first year of the program, there was less physician-administered drug use by patients with prostate cancer, lower drug costs by patients with lung and prostate cancer, fewer visits by patients with breast or colon cancer, and lower office-based costs in all cancers analyzed. However, these savings were largely offset by the costs of these programs.
In the current study, DR. Brooks and colleagues compared the use of supportive care medications – bone-modifying drugs as well as prophylactic white blood cell (WBC) growth factors and antiemetics – in practices that adopted the OCM and those that didn’t.
More specifically, the authors zeroed in on the bone-modifying agent denosumab for patients with breast, lung, or prostate cancer and the WBC growth factor biosimilar filgrastim for those receiving chemotherapy for breast, lung, or colorectal cancer. Prophylactic use of higher-cost neurokinin-1 (NK1) antagonists and long-acting serotonin antagonists for patients receiving chemotherapy for any type of cancer was also evaluated.
The authors evaluated chemotherapy episodes assigned to OCM (n = 201) and comparison practices (n = 534) using Medicare claims from 2013-2019.
There was a total of 255,638 treatment episodes for bone metastases. The authors found that the OCM led to relative reductions in the use of denosumab but not in the overall use of bone-modifying medications, which included the less costly options zoledronic acid and pamidronate. The use of denosumab was similar for OCM and comparison practices during the baseline period, but during the intervention period, there were statistically significant relative reductions in the use of denosumab at OCM practices for breast (-5.0%), prostate (-4.0%), and lung cancer (-4.1%).
For WBC growth factors, 164,310 episodes were included in analyses. The OCM did not affect the use of prophylactic WBC growth factors during breast cancer chemotherapy for those at high risk of febrile neutropenia but did lead to a relative decrease during intermediate-risk chemotherapy (-7.6%). The authors observed no OCM impact on the use of prophylactic WBC growth factors among intermediate-risk lung or colorectal cancer patients. But, during the intervention period, OCM practices did demonstrate an increased use of originator or biosimilar filgrastim (57.3%) compared to other practices (47.6%), and the quarterly rate of increase in the use of the biosimilar grew 2.6 percentage points faster in OCM practices.
The authors report that there were 414,792 treatment episodes involving the use of prophylactic antiemetics. Overall, among patients receiving chemotherapy with high or moderate emetic risk, the OCM led to reductions in the prophylactic use of NK1 antagonists and long-acting serotonin antagonists. The authors report a 6.0 percentage point reduction in the use of NK1 antagonists during high-emetic-risk chemotherapy.
“We found that OCM was associated with meaningful changes in the use of supportive care medications during chemotherapy treatment episodes consistent with value-based care redesign,” the authors conclude. “These impacts on supportive care medication use align with previously reported spending reductions attributable to OCM and suggest that alternative payment models have potential to drive value-based changes in supportive care during cancer treatment.”
The study was supported by CMS. Several of the coauthors have reported relationships with industry, as noted in the article.
A version of this article first appeared on Medscape.com.
The Oncology Care Model (OCM), launched by the Centers for Medicare & Medicaid Services (CMS) with the goal of reducing spending for Medicare beneficiaries, was “associated with meaningful changes in the use of supportive care medications during chemotherapy treatment episodes,” according to new findings.
The OCM led to a statistically significant reduction in the use of denosumab – a pricier bone-modifying drug – by patients with bone metastases without changing the overall use of bone-modifying medications. The OCM also prompted more rapid adoption of a less expensive white blood cell growth factor agent – the biosimilar filgrastim – and more selective use of costly antiemetics as primary prophylaxis for chemotherapy-induced nausea.
study author Gabriel A. Brooks, MD, MPH, of the Dartmouth Institute for Health Policy and Clinical Practice, Geisel School of Medicine, Lebanon, N.H., and colleagues write.
The study was published online Feb. 25 in the Journal of Clinical Oncology.
Since the OCM was launched in 2016, several studies have evaluated whether the alternative payment model reached its goal of reducing spending while improving or maintaining the quality of cancer care.
The results have been decidedly mixed.
As previously reported by this news organization, one study found that after 4 years, the OCM led to a $155 million net loss to Medicare. During that time, physician participation in the program also declined, with the number of practices dropping almost 30% between 2016 and 2020.
Other studies, however, have highlighted more positive results.
One large community practice reported saving Medicare $3 million over the course of 1 year. Another analysis found that among community practices that adopted the OCM, in the first year of the program, there was less physician-administered drug use by patients with prostate cancer, lower drug costs by patients with lung and prostate cancer, fewer visits by patients with breast or colon cancer, and lower office-based costs in all cancers analyzed. However, these savings were largely offset by the costs of these programs.
In the current study, DR. Brooks and colleagues compared the use of supportive care medications – bone-modifying drugs as well as prophylactic white blood cell (WBC) growth factors and antiemetics – in practices that adopted the OCM and those that didn’t.
More specifically, the authors zeroed in on the bone-modifying agent denosumab for patients with breast, lung, or prostate cancer and the WBC growth factor biosimilar filgrastim for those receiving chemotherapy for breast, lung, or colorectal cancer. Prophylactic use of higher-cost neurokinin-1 (NK1) antagonists and long-acting serotonin antagonists for patients receiving chemotherapy for any type of cancer was also evaluated.
The authors evaluated chemotherapy episodes assigned to OCM (n = 201) and comparison practices (n = 534) using Medicare claims from 2013-2019.
There was a total of 255,638 treatment episodes for bone metastases. The authors found that the OCM led to relative reductions in the use of denosumab but not in the overall use of bone-modifying medications, which included the less costly options zoledronic acid and pamidronate. The use of denosumab was similar for OCM and comparison practices during the baseline period, but during the intervention period, there were statistically significant relative reductions in the use of denosumab at OCM practices for breast (-5.0%), prostate (-4.0%), and lung cancer (-4.1%).
For WBC growth factors, 164,310 episodes were included in analyses. The OCM did not affect the use of prophylactic WBC growth factors during breast cancer chemotherapy for those at high risk of febrile neutropenia but did lead to a relative decrease during intermediate-risk chemotherapy (-7.6%). The authors observed no OCM impact on the use of prophylactic WBC growth factors among intermediate-risk lung or colorectal cancer patients. But, during the intervention period, OCM practices did demonstrate an increased use of originator or biosimilar filgrastim (57.3%) compared to other practices (47.6%), and the quarterly rate of increase in the use of the biosimilar grew 2.6 percentage points faster in OCM practices.
The authors report that there were 414,792 treatment episodes involving the use of prophylactic antiemetics. Overall, among patients receiving chemotherapy with high or moderate emetic risk, the OCM led to reductions in the prophylactic use of NK1 antagonists and long-acting serotonin antagonists. The authors report a 6.0 percentage point reduction in the use of NK1 antagonists during high-emetic-risk chemotherapy.
“We found that OCM was associated with meaningful changes in the use of supportive care medications during chemotherapy treatment episodes consistent with value-based care redesign,” the authors conclude. “These impacts on supportive care medication use align with previously reported spending reductions attributable to OCM and suggest that alternative payment models have potential to drive value-based changes in supportive care during cancer treatment.”
The study was supported by CMS. Several of the coauthors have reported relationships with industry, as noted in the article.
A version of this article first appeared on Medscape.com.
The Oncology Care Model (OCM), launched by the Centers for Medicare & Medicaid Services (CMS) with the goal of reducing spending for Medicare beneficiaries, was “associated with meaningful changes in the use of supportive care medications during chemotherapy treatment episodes,” according to new findings.
The OCM led to a statistically significant reduction in the use of denosumab – a pricier bone-modifying drug – by patients with bone metastases without changing the overall use of bone-modifying medications. The OCM also prompted more rapid adoption of a less expensive white blood cell growth factor agent – the biosimilar filgrastim – and more selective use of costly antiemetics as primary prophylaxis for chemotherapy-induced nausea.
study author Gabriel A. Brooks, MD, MPH, of the Dartmouth Institute for Health Policy and Clinical Practice, Geisel School of Medicine, Lebanon, N.H., and colleagues write.
The study was published online Feb. 25 in the Journal of Clinical Oncology.
Since the OCM was launched in 2016, several studies have evaluated whether the alternative payment model reached its goal of reducing spending while improving or maintaining the quality of cancer care.
The results have been decidedly mixed.
As previously reported by this news organization, one study found that after 4 years, the OCM led to a $155 million net loss to Medicare. During that time, physician participation in the program also declined, with the number of practices dropping almost 30% between 2016 and 2020.
Other studies, however, have highlighted more positive results.
One large community practice reported saving Medicare $3 million over the course of 1 year. Another analysis found that among community practices that adopted the OCM, in the first year of the program, there was less physician-administered drug use by patients with prostate cancer, lower drug costs by patients with lung and prostate cancer, fewer visits by patients with breast or colon cancer, and lower office-based costs in all cancers analyzed. However, these savings were largely offset by the costs of these programs.
In the current study, DR. Brooks and colleagues compared the use of supportive care medications – bone-modifying drugs as well as prophylactic white blood cell (WBC) growth factors and antiemetics – in practices that adopted the OCM and those that didn’t.
More specifically, the authors zeroed in on the bone-modifying agent denosumab for patients with breast, lung, or prostate cancer and the WBC growth factor biosimilar filgrastim for those receiving chemotherapy for breast, lung, or colorectal cancer. Prophylactic use of higher-cost neurokinin-1 (NK1) antagonists and long-acting serotonin antagonists for patients receiving chemotherapy for any type of cancer was also evaluated.
The authors evaluated chemotherapy episodes assigned to OCM (n = 201) and comparison practices (n = 534) using Medicare claims from 2013-2019.
There was a total of 255,638 treatment episodes for bone metastases. The authors found that the OCM led to relative reductions in the use of denosumab but not in the overall use of bone-modifying medications, which included the less costly options zoledronic acid and pamidronate. The use of denosumab was similar for OCM and comparison practices during the baseline period, but during the intervention period, there were statistically significant relative reductions in the use of denosumab at OCM practices for breast (-5.0%), prostate (-4.0%), and lung cancer (-4.1%).
For WBC growth factors, 164,310 episodes were included in analyses. The OCM did not affect the use of prophylactic WBC growth factors during breast cancer chemotherapy for those at high risk of febrile neutropenia but did lead to a relative decrease during intermediate-risk chemotherapy (-7.6%). The authors observed no OCM impact on the use of prophylactic WBC growth factors among intermediate-risk lung or colorectal cancer patients. But, during the intervention period, OCM practices did demonstrate an increased use of originator or biosimilar filgrastim (57.3%) compared to other practices (47.6%), and the quarterly rate of increase in the use of the biosimilar grew 2.6 percentage points faster in OCM practices.
The authors report that there were 414,792 treatment episodes involving the use of prophylactic antiemetics. Overall, among patients receiving chemotherapy with high or moderate emetic risk, the OCM led to reductions in the prophylactic use of NK1 antagonists and long-acting serotonin antagonists. The authors report a 6.0 percentage point reduction in the use of NK1 antagonists during high-emetic-risk chemotherapy.
“We found that OCM was associated with meaningful changes in the use of supportive care medications during chemotherapy treatment episodes consistent with value-based care redesign,” the authors conclude. “These impacts on supportive care medication use align with previously reported spending reductions attributable to OCM and suggest that alternative payment models have potential to drive value-based changes in supportive care during cancer treatment.”
The study was supported by CMS. Several of the coauthors have reported relationships with industry, as noted in the article.
A version of this article first appeared on Medscape.com.
FROM JOURNAL OF CLINICAL ONCOLOGY