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CAR T-cell Trial for Children With Lupus Expected to Begin This Summer
The US Food and Drug Administration (FDA) has approved the launch of the first clinical trial for chimeric antigen receptor (CAR) T-cell therapy in children with systemic lupus erythematosus.
The trial, called Reversing Autoimmunity through Cell Therapy (REACT-01), will take place at Seattle Children’s Hospital in Washington State and is expected to begin this summer.
The CAR-T therapy will target CD19 positive B-cells, an approach that has had promising results in a small number of adult patients. While the FDA has approved a number of clinical trials using CAR-T therapy to treat autoimmune diseases in adults, this is the first authorization for a CAR T-cell therapy trial to treat autoimmune disease in children.
REACT-01 will enroll 12 individuals under 18 years of age, Shaun W. Jackson, MD, PhD, the principal investigator of the trial and attending physician in Pediatric Nephrology and Pediatric Rheumatology at Seattle Children’s Hospital, told this news organization.
The trial will be initiated in separate phases, using three age cohorts. The first phase will enroll three individuals aged at least 17 years, before moving to the second phase and enrolling three individuals aged 12-17 years. Then, phase 3 will also include children aged 5-12 years.
To be eligible for the trial, participants must have failed at least two standard immunosuppressive therapies as well as have evidence of active lupus disease affecting a major organ system, such as the heart, lungs, and kidneys.
“Seattle Children’s Hospital will be the only site for this study, although patients can travel to Seattle to receive the therapy and then return back to their primary center for ongoing care,” Dr. Jackson said.
A version of this article appeared on Medscape.com.
The US Food and Drug Administration (FDA) has approved the launch of the first clinical trial for chimeric antigen receptor (CAR) T-cell therapy in children with systemic lupus erythematosus.
The trial, called Reversing Autoimmunity through Cell Therapy (REACT-01), will take place at Seattle Children’s Hospital in Washington State and is expected to begin this summer.
The CAR-T therapy will target CD19 positive B-cells, an approach that has had promising results in a small number of adult patients. While the FDA has approved a number of clinical trials using CAR-T therapy to treat autoimmune diseases in adults, this is the first authorization for a CAR T-cell therapy trial to treat autoimmune disease in children.
REACT-01 will enroll 12 individuals under 18 years of age, Shaun W. Jackson, MD, PhD, the principal investigator of the trial and attending physician in Pediatric Nephrology and Pediatric Rheumatology at Seattle Children’s Hospital, told this news organization.
The trial will be initiated in separate phases, using three age cohorts. The first phase will enroll three individuals aged at least 17 years, before moving to the second phase and enrolling three individuals aged 12-17 years. Then, phase 3 will also include children aged 5-12 years.
To be eligible for the trial, participants must have failed at least two standard immunosuppressive therapies as well as have evidence of active lupus disease affecting a major organ system, such as the heart, lungs, and kidneys.
“Seattle Children’s Hospital will be the only site for this study, although patients can travel to Seattle to receive the therapy and then return back to their primary center for ongoing care,” Dr. Jackson said.
A version of this article appeared on Medscape.com.
The US Food and Drug Administration (FDA) has approved the launch of the first clinical trial for chimeric antigen receptor (CAR) T-cell therapy in children with systemic lupus erythematosus.
The trial, called Reversing Autoimmunity through Cell Therapy (REACT-01), will take place at Seattle Children’s Hospital in Washington State and is expected to begin this summer.
The CAR-T therapy will target CD19 positive B-cells, an approach that has had promising results in a small number of adult patients. While the FDA has approved a number of clinical trials using CAR-T therapy to treat autoimmune diseases in adults, this is the first authorization for a CAR T-cell therapy trial to treat autoimmune disease in children.
REACT-01 will enroll 12 individuals under 18 years of age, Shaun W. Jackson, MD, PhD, the principal investigator of the trial and attending physician in Pediatric Nephrology and Pediatric Rheumatology at Seattle Children’s Hospital, told this news organization.
The trial will be initiated in separate phases, using three age cohorts. The first phase will enroll three individuals aged at least 17 years, before moving to the second phase and enrolling three individuals aged 12-17 years. Then, phase 3 will also include children aged 5-12 years.
To be eligible for the trial, participants must have failed at least two standard immunosuppressive therapies as well as have evidence of active lupus disease affecting a major organ system, such as the heart, lungs, and kidneys.
“Seattle Children’s Hospital will be the only site for this study, although patients can travel to Seattle to receive the therapy and then return back to their primary center for ongoing care,” Dr. Jackson said.
A version of this article appeared on Medscape.com.
What to Know About the Next-Gen FIT for CRC Screening
These new tests aren’t radical departures from the standard FIT. Like the standard test, the multitarget FIT uses antibodies to test for hemoglobin in stool samples. But these multitarget approaches take the standard FIT a step further by testing for additional DNA, RNA, or protein biomarkers associated with CRC to help improve early detection.
Currently, the US Preventive Services Task Force (USPSTF) recommends two FIT tests — standard FIT and stool FIT-DNA — as well as a third noninvasive CRC screening test, guaiac fecal occult blood test (gFOBT). gFOBT detects heme, a component of hemoglobin, through a chemical reaction.
But both standard FIT and stool FIT-DNA come with caveats. Compared to the standard test, FIT-DNA tends to be better at detecting traces of blood in the stool, and thus can uncover more instances of CRC or other advanced lesions. The flipside is that the DNA test also often leads to more false-positive findings.
In fact, the American College of Physicians does not recommend stool FIT-DNA for screening, citing issues such as cost — more than $600 per test vs about $30 for standard FIT — and the greater likelihood of false-positives compared with both standard FIT and gFOBT.
Given these trade-offs with current noninvasive screening options, developing a FIT option that can improve early detection of CRC and advanced precancerous lesions without increasing false-positives could make a big difference in outcomes.
Three new noninvasive multitarget tests under investigation — an updated DNA-based test, Cologuard 2.0 (Exact Sciences; Madison, WI); an RNA-based test, ColoSense (Geneoscopy; St Louis, MO); and a protein-based test from CRCbioscreen (Amsterdam, the Netherlands) — may be able to do just that.
Cologuard 2.0: Multitarget Stool DNA-Based Test
An updated version of the stool FIT-DNA is currently under development. Dubbed Next Generation Cologuard, or Cologuard 2.0, this multitarget test detects three novel methylated DNA markers along with fecal hemoglobin.
In a recent trial comparing Cologuard 2.0 vs standard FIT, 20,176 participants aged 40 years or older were screened with Cologuard 2.0 as well as standard FIT before they all also received a colonoscopy. The researchers compared findings with Cologuard 2.0 and standard FIT, which used a positivity cutoff ≥ 20 mcg hemoglobin/g feces.
The researchers then assessed Cologuard 2.0’s sensitivity (a gauge of how well it detects disease that is truly present) and specificity (a measure of how well a test indicates the absence of disease when no disease is present) compared with standard FIT and the original Cologuard test.
Overall, Cologuard 2.0 demonstrated better sensitivity for CRC than did standard FIT (93.9% vs 67.3%, respectively) and for advanced precancerous lesions (43.4% vs 23.3%). The next-generation test, for instance, identified 92 of 98 participants with colonoscopy-confirmed CRC diagnoses vs 66 cases using standard FIT.
Compared with the original Cologuard, Cologuard 2.0’s sensitivity improved slightly for CRC, from 92% to 93.9%,; for advanced precancerous lesions, from 42% to 43.4%; and for high-grade dysplasia, from 69% to 75%. Specificity also improved with the latest version, from 87% to 90.6%.
However, Cologuard 2.0’s specificity for advanced neoplasia was worse than that of standard FIT (90.6% vs 94.8%, respectively), which would increase the likelihood of false-positive findings.
Despite its lower specificity compared with standard FIT, Cologuard 2.0 has several advantages. The test can identify more people with CRC and advanced precancerous lesions than the standard test and can lead to fewer false-positives than the original Cologuard test.
Cologuard maker Exact Sciences has submitted trial data to the US Food and Drug Administration (FDA) for approval.
Multitarget Stool RNA-Based Test
ColoSense, an RNA-based stool test, looks for eight RNA biomarkers associated with CRC.
The company says that RNA-based testing has an advantage over DNA biomarker assays, such as the currently marketed Cologuard test, because it isn›t subject to the age-related changes in DNA methylation that can throw off the results from DNA assays.
Like Cologuard 2.0, Geneoscopy’s Colosense test is under review by the FDA.
The data Geneoscopy submitted to the FDA came from the CRC-PREVENT trial, which included 8920 participants who were screened with both ColoSense and standard FIT before all had a colonoscopy. The participants ranged in age from 45 to 90 years, with 22% between 45 and 50 years old, a population recently added to the USPSTF screening recommendations.
ColoSense showed higher sensitivity than standard FIT for the presence of CRC (94% vs 78%, respectively) and advanced adenomas (46% vs 29%). In the group aged 45-50 years, the RNA-based test had a sensitivity of 100% for CRC, correctly identifying all five people with colonoscopy-confirmed CRC, and 45% for advanced adenomas.
However, ColoSense was less specific than standard FIT compared with negative colonoscopy findings (88% vs 96%, respectively) and negative findings for advanced lesions or CRC (85.5% vs 94.9%); thus, it was more likely to lead to false-positive results.
Overall, the investigators said ColoSense is comparable to Cologuard — its chief market rival — in terms of sensitivity for CRC and advanced adenomas but has higher sensitivity for colorectal neoplasia in people aged 50 years or younger.
Multitarget Protein-Based Test
The multitarget protein-based FIT uses antibodies to test for two additional proteins: calprotectin, an inflammatory marker associated with CRC, and serpin family F member 2, a protease inhibitor thought to be upregulated in colon cancer.
A 2021 study of 1284 patients found that the sensitivity of the multitarget protein-based test was 42.9% for advanced neoplasias compared with 37.3% with standard FIT. Its specificity was similar to that of standard FIT, at 96.6% for advanced neoplasias.
In a more recent report published in The Lancet Oncology, the team modeled three scenarios comparing the two FIT tests. These scenarios used different cutoff values for a test to be positive for CRC or an advanced lesion.
Overall, the analysis included stool samples from 13,187 patients aged 55-75 years who were in the Netherlands’ national CRC screening program. Stool samples were evaluated with both the multitarget test and the standard FIT, using a positivity cutoff ≥ 47 mcg hemoglobin/g feces. Colonoscopy data were available for only 1270 participants.
In scenario 1, the multitarget test had a lower threshold for a positive test and consequently identified more precancerous lesions than the standard FIT (828 vs 354, respectively). The multitarget FIT identified a few more CRC cases: Of 29 colonoscopy-confirmed CRC cases, the multitarget FIT identified 26 vs 23 with standard FIT.
But the multitarget FIT also had more than double the number of false-positives than the standard FIT (347 vs 161, respectively).
Perhaps the most telling comparison occurred in scenario 2, with both tests set at the same low positivity threshold to minimize false-positives.
As expected, the two tests had similar positivity rates for advanced lesions, with the multitarget test correctly identifying 22 of 29 people with CRC, one fewer than the standard test. The protein-based test identified slightly more people with advanced lesions (156 vs 136 with the standard test), leading to a higher sensitivity for advanced lesions.
Most notably, the protein-based test resulted in fewer false-positives than did the standard test (295 vs 311, respectively) , resulting in a slightly higher specificity.
In this scenario, “a single screening round might not have the biggest impact on cancer incidence and mortality,” the authors said, but the higher detection rate would still accumulate over 20 years of testing. The authors estimated that, under this scenario, substituting the multitarget FIT for the standard test in the Netherlands’ CRC screening program could reduce CRC incidence by 5% and CRC mortality by 4%.
Gerrit Meijer, MD, PhD, a pathologist at the Netherlands Cancer Institute, and colleagues recently launched a company called CRCbioscreen to commercialize this multitarget FIT for large-scale programs. The company›s priority is to develop and validate a clinical-grade test to sell to federal governments with national screening programs, such as those throughout Europe, Australia, and Asia, Dr. Meijer told this news organization. Dr. Meijer expects this process will take about 4 years.
The test will be developed for the US market, but with no nationwide screening program in the United States, future availability will depend on interest from providers and institutions, noted Dr. Meijer, who is also chief scientific officer at CRCbioscreen.
Overall, these three new multitarget stool-based CRC screening tests could help catch more cancers and advanced precancerous lesions. And, if the tests have a high enough specificity, a negative test result could also allow people to forgo screening colonoscopy.
Still, people with a positive FIT finding would require follow-up colonoscopy, but about 10% of patients decline colonoscopy following an abnormal FIT, Mark A. Lewis, MD, director of gastrointestinal oncology at Intermountain Health in Murray, Utah, told this news organization last year. That means that even if precancerous lesions and CRC are being caught earlier, treatment can’t be started unless people follow through with colonoscopy.
A version of this article appeared on Medscape.com.
These new tests aren’t radical departures from the standard FIT. Like the standard test, the multitarget FIT uses antibodies to test for hemoglobin in stool samples. But these multitarget approaches take the standard FIT a step further by testing for additional DNA, RNA, or protein biomarkers associated with CRC to help improve early detection.
Currently, the US Preventive Services Task Force (USPSTF) recommends two FIT tests — standard FIT and stool FIT-DNA — as well as a third noninvasive CRC screening test, guaiac fecal occult blood test (gFOBT). gFOBT detects heme, a component of hemoglobin, through a chemical reaction.
But both standard FIT and stool FIT-DNA come with caveats. Compared to the standard test, FIT-DNA tends to be better at detecting traces of blood in the stool, and thus can uncover more instances of CRC or other advanced lesions. The flipside is that the DNA test also often leads to more false-positive findings.
In fact, the American College of Physicians does not recommend stool FIT-DNA for screening, citing issues such as cost — more than $600 per test vs about $30 for standard FIT — and the greater likelihood of false-positives compared with both standard FIT and gFOBT.
Given these trade-offs with current noninvasive screening options, developing a FIT option that can improve early detection of CRC and advanced precancerous lesions without increasing false-positives could make a big difference in outcomes.
Three new noninvasive multitarget tests under investigation — an updated DNA-based test, Cologuard 2.0 (Exact Sciences; Madison, WI); an RNA-based test, ColoSense (Geneoscopy; St Louis, MO); and a protein-based test from CRCbioscreen (Amsterdam, the Netherlands) — may be able to do just that.
Cologuard 2.0: Multitarget Stool DNA-Based Test
An updated version of the stool FIT-DNA is currently under development. Dubbed Next Generation Cologuard, or Cologuard 2.0, this multitarget test detects three novel methylated DNA markers along with fecal hemoglobin.
In a recent trial comparing Cologuard 2.0 vs standard FIT, 20,176 participants aged 40 years or older were screened with Cologuard 2.0 as well as standard FIT before they all also received a colonoscopy. The researchers compared findings with Cologuard 2.0 and standard FIT, which used a positivity cutoff ≥ 20 mcg hemoglobin/g feces.
The researchers then assessed Cologuard 2.0’s sensitivity (a gauge of how well it detects disease that is truly present) and specificity (a measure of how well a test indicates the absence of disease when no disease is present) compared with standard FIT and the original Cologuard test.
Overall, Cologuard 2.0 demonstrated better sensitivity for CRC than did standard FIT (93.9% vs 67.3%, respectively) and for advanced precancerous lesions (43.4% vs 23.3%). The next-generation test, for instance, identified 92 of 98 participants with colonoscopy-confirmed CRC diagnoses vs 66 cases using standard FIT.
Compared with the original Cologuard, Cologuard 2.0’s sensitivity improved slightly for CRC, from 92% to 93.9%,; for advanced precancerous lesions, from 42% to 43.4%; and for high-grade dysplasia, from 69% to 75%. Specificity also improved with the latest version, from 87% to 90.6%.
However, Cologuard 2.0’s specificity for advanced neoplasia was worse than that of standard FIT (90.6% vs 94.8%, respectively), which would increase the likelihood of false-positive findings.
Despite its lower specificity compared with standard FIT, Cologuard 2.0 has several advantages. The test can identify more people with CRC and advanced precancerous lesions than the standard test and can lead to fewer false-positives than the original Cologuard test.
Cologuard maker Exact Sciences has submitted trial data to the US Food and Drug Administration (FDA) for approval.
Multitarget Stool RNA-Based Test
ColoSense, an RNA-based stool test, looks for eight RNA biomarkers associated with CRC.
The company says that RNA-based testing has an advantage over DNA biomarker assays, such as the currently marketed Cologuard test, because it isn›t subject to the age-related changes in DNA methylation that can throw off the results from DNA assays.
Like Cologuard 2.0, Geneoscopy’s Colosense test is under review by the FDA.
The data Geneoscopy submitted to the FDA came from the CRC-PREVENT trial, which included 8920 participants who were screened with both ColoSense and standard FIT before all had a colonoscopy. The participants ranged in age from 45 to 90 years, with 22% between 45 and 50 years old, a population recently added to the USPSTF screening recommendations.
ColoSense showed higher sensitivity than standard FIT for the presence of CRC (94% vs 78%, respectively) and advanced adenomas (46% vs 29%). In the group aged 45-50 years, the RNA-based test had a sensitivity of 100% for CRC, correctly identifying all five people with colonoscopy-confirmed CRC, and 45% for advanced adenomas.
However, ColoSense was less specific than standard FIT compared with negative colonoscopy findings (88% vs 96%, respectively) and negative findings for advanced lesions or CRC (85.5% vs 94.9%); thus, it was more likely to lead to false-positive results.
Overall, the investigators said ColoSense is comparable to Cologuard — its chief market rival — in terms of sensitivity for CRC and advanced adenomas but has higher sensitivity for colorectal neoplasia in people aged 50 years or younger.
Multitarget Protein-Based Test
The multitarget protein-based FIT uses antibodies to test for two additional proteins: calprotectin, an inflammatory marker associated with CRC, and serpin family F member 2, a protease inhibitor thought to be upregulated in colon cancer.
A 2021 study of 1284 patients found that the sensitivity of the multitarget protein-based test was 42.9% for advanced neoplasias compared with 37.3% with standard FIT. Its specificity was similar to that of standard FIT, at 96.6% for advanced neoplasias.
In a more recent report published in The Lancet Oncology, the team modeled three scenarios comparing the two FIT tests. These scenarios used different cutoff values for a test to be positive for CRC or an advanced lesion.
Overall, the analysis included stool samples from 13,187 patients aged 55-75 years who were in the Netherlands’ national CRC screening program. Stool samples were evaluated with both the multitarget test and the standard FIT, using a positivity cutoff ≥ 47 mcg hemoglobin/g feces. Colonoscopy data were available for only 1270 participants.
In scenario 1, the multitarget test had a lower threshold for a positive test and consequently identified more precancerous lesions than the standard FIT (828 vs 354, respectively). The multitarget FIT identified a few more CRC cases: Of 29 colonoscopy-confirmed CRC cases, the multitarget FIT identified 26 vs 23 with standard FIT.
But the multitarget FIT also had more than double the number of false-positives than the standard FIT (347 vs 161, respectively).
Perhaps the most telling comparison occurred in scenario 2, with both tests set at the same low positivity threshold to minimize false-positives.
As expected, the two tests had similar positivity rates for advanced lesions, with the multitarget test correctly identifying 22 of 29 people with CRC, one fewer than the standard test. The protein-based test identified slightly more people with advanced lesions (156 vs 136 with the standard test), leading to a higher sensitivity for advanced lesions.
Most notably, the protein-based test resulted in fewer false-positives than did the standard test (295 vs 311, respectively) , resulting in a slightly higher specificity.
In this scenario, “a single screening round might not have the biggest impact on cancer incidence and mortality,” the authors said, but the higher detection rate would still accumulate over 20 years of testing. The authors estimated that, under this scenario, substituting the multitarget FIT for the standard test in the Netherlands’ CRC screening program could reduce CRC incidence by 5% and CRC mortality by 4%.
Gerrit Meijer, MD, PhD, a pathologist at the Netherlands Cancer Institute, and colleagues recently launched a company called CRCbioscreen to commercialize this multitarget FIT for large-scale programs. The company›s priority is to develop and validate a clinical-grade test to sell to federal governments with national screening programs, such as those throughout Europe, Australia, and Asia, Dr. Meijer told this news organization. Dr. Meijer expects this process will take about 4 years.
The test will be developed for the US market, but with no nationwide screening program in the United States, future availability will depend on interest from providers and institutions, noted Dr. Meijer, who is also chief scientific officer at CRCbioscreen.
Overall, these three new multitarget stool-based CRC screening tests could help catch more cancers and advanced precancerous lesions. And, if the tests have a high enough specificity, a negative test result could also allow people to forgo screening colonoscopy.
Still, people with a positive FIT finding would require follow-up colonoscopy, but about 10% of patients decline colonoscopy following an abnormal FIT, Mark A. Lewis, MD, director of gastrointestinal oncology at Intermountain Health in Murray, Utah, told this news organization last year. That means that even if precancerous lesions and CRC are being caught earlier, treatment can’t be started unless people follow through with colonoscopy.
A version of this article appeared on Medscape.com.
These new tests aren’t radical departures from the standard FIT. Like the standard test, the multitarget FIT uses antibodies to test for hemoglobin in stool samples. But these multitarget approaches take the standard FIT a step further by testing for additional DNA, RNA, or protein biomarkers associated with CRC to help improve early detection.
Currently, the US Preventive Services Task Force (USPSTF) recommends two FIT tests — standard FIT and stool FIT-DNA — as well as a third noninvasive CRC screening test, guaiac fecal occult blood test (gFOBT). gFOBT detects heme, a component of hemoglobin, through a chemical reaction.
But both standard FIT and stool FIT-DNA come with caveats. Compared to the standard test, FIT-DNA tends to be better at detecting traces of blood in the stool, and thus can uncover more instances of CRC or other advanced lesions. The flipside is that the DNA test also often leads to more false-positive findings.
In fact, the American College of Physicians does not recommend stool FIT-DNA for screening, citing issues such as cost — more than $600 per test vs about $30 for standard FIT — and the greater likelihood of false-positives compared with both standard FIT and gFOBT.
Given these trade-offs with current noninvasive screening options, developing a FIT option that can improve early detection of CRC and advanced precancerous lesions without increasing false-positives could make a big difference in outcomes.
Three new noninvasive multitarget tests under investigation — an updated DNA-based test, Cologuard 2.0 (Exact Sciences; Madison, WI); an RNA-based test, ColoSense (Geneoscopy; St Louis, MO); and a protein-based test from CRCbioscreen (Amsterdam, the Netherlands) — may be able to do just that.
Cologuard 2.0: Multitarget Stool DNA-Based Test
An updated version of the stool FIT-DNA is currently under development. Dubbed Next Generation Cologuard, or Cologuard 2.0, this multitarget test detects three novel methylated DNA markers along with fecal hemoglobin.
In a recent trial comparing Cologuard 2.0 vs standard FIT, 20,176 participants aged 40 years or older were screened with Cologuard 2.0 as well as standard FIT before they all also received a colonoscopy. The researchers compared findings with Cologuard 2.0 and standard FIT, which used a positivity cutoff ≥ 20 mcg hemoglobin/g feces.
The researchers then assessed Cologuard 2.0’s sensitivity (a gauge of how well it detects disease that is truly present) and specificity (a measure of how well a test indicates the absence of disease when no disease is present) compared with standard FIT and the original Cologuard test.
Overall, Cologuard 2.0 demonstrated better sensitivity for CRC than did standard FIT (93.9% vs 67.3%, respectively) and for advanced precancerous lesions (43.4% vs 23.3%). The next-generation test, for instance, identified 92 of 98 participants with colonoscopy-confirmed CRC diagnoses vs 66 cases using standard FIT.
Compared with the original Cologuard, Cologuard 2.0’s sensitivity improved slightly for CRC, from 92% to 93.9%,; for advanced precancerous lesions, from 42% to 43.4%; and for high-grade dysplasia, from 69% to 75%. Specificity also improved with the latest version, from 87% to 90.6%.
However, Cologuard 2.0’s specificity for advanced neoplasia was worse than that of standard FIT (90.6% vs 94.8%, respectively), which would increase the likelihood of false-positive findings.
Despite its lower specificity compared with standard FIT, Cologuard 2.0 has several advantages. The test can identify more people with CRC and advanced precancerous lesions than the standard test and can lead to fewer false-positives than the original Cologuard test.
Cologuard maker Exact Sciences has submitted trial data to the US Food and Drug Administration (FDA) for approval.
Multitarget Stool RNA-Based Test
ColoSense, an RNA-based stool test, looks for eight RNA biomarkers associated with CRC.
The company says that RNA-based testing has an advantage over DNA biomarker assays, such as the currently marketed Cologuard test, because it isn›t subject to the age-related changes in DNA methylation that can throw off the results from DNA assays.
Like Cologuard 2.0, Geneoscopy’s Colosense test is under review by the FDA.
The data Geneoscopy submitted to the FDA came from the CRC-PREVENT trial, which included 8920 participants who were screened with both ColoSense and standard FIT before all had a colonoscopy. The participants ranged in age from 45 to 90 years, with 22% between 45 and 50 years old, a population recently added to the USPSTF screening recommendations.
ColoSense showed higher sensitivity than standard FIT for the presence of CRC (94% vs 78%, respectively) and advanced adenomas (46% vs 29%). In the group aged 45-50 years, the RNA-based test had a sensitivity of 100% for CRC, correctly identifying all five people with colonoscopy-confirmed CRC, and 45% for advanced adenomas.
However, ColoSense was less specific than standard FIT compared with negative colonoscopy findings (88% vs 96%, respectively) and negative findings for advanced lesions or CRC (85.5% vs 94.9%); thus, it was more likely to lead to false-positive results.
Overall, the investigators said ColoSense is comparable to Cologuard — its chief market rival — in terms of sensitivity for CRC and advanced adenomas but has higher sensitivity for colorectal neoplasia in people aged 50 years or younger.
Multitarget Protein-Based Test
The multitarget protein-based FIT uses antibodies to test for two additional proteins: calprotectin, an inflammatory marker associated with CRC, and serpin family F member 2, a protease inhibitor thought to be upregulated in colon cancer.
A 2021 study of 1284 patients found that the sensitivity of the multitarget protein-based test was 42.9% for advanced neoplasias compared with 37.3% with standard FIT. Its specificity was similar to that of standard FIT, at 96.6% for advanced neoplasias.
In a more recent report published in The Lancet Oncology, the team modeled three scenarios comparing the two FIT tests. These scenarios used different cutoff values for a test to be positive for CRC or an advanced lesion.
Overall, the analysis included stool samples from 13,187 patients aged 55-75 years who were in the Netherlands’ national CRC screening program. Stool samples were evaluated with both the multitarget test and the standard FIT, using a positivity cutoff ≥ 47 mcg hemoglobin/g feces. Colonoscopy data were available for only 1270 participants.
In scenario 1, the multitarget test had a lower threshold for a positive test and consequently identified more precancerous lesions than the standard FIT (828 vs 354, respectively). The multitarget FIT identified a few more CRC cases: Of 29 colonoscopy-confirmed CRC cases, the multitarget FIT identified 26 vs 23 with standard FIT.
But the multitarget FIT also had more than double the number of false-positives than the standard FIT (347 vs 161, respectively).
Perhaps the most telling comparison occurred in scenario 2, with both tests set at the same low positivity threshold to minimize false-positives.
As expected, the two tests had similar positivity rates for advanced lesions, with the multitarget test correctly identifying 22 of 29 people with CRC, one fewer than the standard test. The protein-based test identified slightly more people with advanced lesions (156 vs 136 with the standard test), leading to a higher sensitivity for advanced lesions.
Most notably, the protein-based test resulted in fewer false-positives than did the standard test (295 vs 311, respectively) , resulting in a slightly higher specificity.
In this scenario, “a single screening round might not have the biggest impact on cancer incidence and mortality,” the authors said, but the higher detection rate would still accumulate over 20 years of testing. The authors estimated that, under this scenario, substituting the multitarget FIT for the standard test in the Netherlands’ CRC screening program could reduce CRC incidence by 5% and CRC mortality by 4%.
Gerrit Meijer, MD, PhD, a pathologist at the Netherlands Cancer Institute, and colleagues recently launched a company called CRCbioscreen to commercialize this multitarget FIT for large-scale programs. The company›s priority is to develop and validate a clinical-grade test to sell to federal governments with national screening programs, such as those throughout Europe, Australia, and Asia, Dr. Meijer told this news organization. Dr. Meijer expects this process will take about 4 years.
The test will be developed for the US market, but with no nationwide screening program in the United States, future availability will depend on interest from providers and institutions, noted Dr. Meijer, who is also chief scientific officer at CRCbioscreen.
Overall, these three new multitarget stool-based CRC screening tests could help catch more cancers and advanced precancerous lesions. And, if the tests have a high enough specificity, a negative test result could also allow people to forgo screening colonoscopy.
Still, people with a positive FIT finding would require follow-up colonoscopy, but about 10% of patients decline colonoscopy following an abnormal FIT, Mark A. Lewis, MD, director of gastrointestinal oncology at Intermountain Health in Murray, Utah, told this news organization last year. That means that even if precancerous lesions and CRC are being caught earlier, treatment can’t be started unless people follow through with colonoscopy.
A version of this article appeared on Medscape.com.
ALL: Which Life-Saving Tx Is Best?
The comparative benefits and limitations of these two treatments for r/r ALL were a topic for discussion at the Great Debates & Updates Hematological Malignancies conference, held April 5-6 in New York City.
“Every single patient with ALL should benefit from bispecific antibodies before getting CAR-T cells, and I want to make the case that everybody should get CAR T as well. But they should get blinatumomab before they get CAR T,” said Elias Jabbour, MD, of the MD Anderson Cancer Center at The University of Texas in Houston, whose presentation focused on the merits of bispecific antibodies.
His argument was based on data indicating that patients have better chances of long-term remission with the use of bispecific antibodies when they are administered in an earlier round of salvage treatment — and the fact that patients who are not cured with these drugs can still achieve a lower disease burden and perform better on CAR T-cell therapy than those who don’t receive the drugs.
“When blinatumomab is used as a consolidation during the first salvage treatment and spaces out transplantation, 3-year overall survival increases in the relapse setting, deepening responses and reducing the rate of VOD (veno-occlusive disease). The safety and efficacy of CAR T depends on a disease burden. If you have a minimal residual disease (MRD), you have a safer outcome and a better outcome in the long run,” Dr. Jabbour explained.
This point of view is supported by data from the treatment of patients r/r ALL with low intensity chemotherapy + inotuzumab ozogamicin (Besponsa; Pfizer) +/- blinatumomab (Blincyto; Amgen), knows as Mini-HCVD + Ino +/-Blina. Trial members achieved a median overall survival (OS) rate of 17 months, a 3-year survival rate of 42%, and an overall MRD negativity rate of 85%.
Dr. Jabbour noted that blinatumomab has its limitations. Generally, this treatment is administered intravenously every few weeks and can be cumbersome for patients who must travel to an infusion center. However, data from a phase 1b trial of single agent subcutaneous blinatumomab for advanced ALL has demonstrated that this formulation can be effective and can lead to MRD negativity, possibly paving the way for easier administration of the drug.
Aditi Shastri, MD, a leukemia specialist at New York’s Montefiore Medical Center who attended the debate, agreed that the data presented did support Dr. Jabbour’s contention that subcutaneous blinatumomab could make treatment available to even more people with r/r ALL. “It’s easier to administer than the blina pump and could act as a bridge to curative therapies like AlloHSCT,” she said.
Jae Park, MD, a leukemia and cellular therapy specialist at Memorial Sloan Kettering Cancer Center in New York City, argued that CAR T is the most potent therapy for r/r ALL. Dr. Park agreed that inotuzumab and blinatumomab have yielded tremendous progress in the treatment of patients with r/r ALL, but he noted that bispecific antibodies lack some of the advantages of CAR T.
Dr. Park said that the biggest difference between the two therapies is that CAR T requires but a single infusion of a living drug. Patients do need to stay close to treatment centers to receive treatment for toxicities, but after about 28 days, they can go home and be monitored from a distance. Furthermore, patients may start by receiving 1 million T-cells, but those cells exponentially expand 100,000- to 1,000,000-fold, meaning that the T-cells to treat cancer have the potential to persist for months and sometimes years.
Furthermore, results from ZUMA-3 Trial of the CD19-targeting CAR T-Cell therapy brexucabtagene autoleucel (Tecartus; Kite Pharma) suggest that CAR T outperforms Mini-HCVD + Ino +/-Blina in patients with r/r ALL. Participants in the trial showed an overall response rate around 80%, a 71% complete response rate, and a median OS of 25.4 months. Patients who achieved a complete response had an even better median OS of 47 months. Although this was not a head-to-head trial with Mini-HCVD + Ino +/-Blina, if the plateau of long-term survivors continues, “this drug could be set apart from treatment with monoclonal antibodies,” Dr. Park said.
However, brexucabtagene autoleucel is not a cure or even an option for all patients. Some patients are too frail to get the drug, and they risk experiencing cytokine release syndrome (CRS). Data from the FELIX study suggest that the CAR T-cell treatment Obe-cel could offer a safety profile that reduces the risk of serious side effects while remaining effective at treating r/r ALL. Obe-cel showed efficacy very similar to that of brexucabtagene autoleucel, with a 70%-80% response rate, and only 2% of patients experienced CRS.
Dr. Park noted that the next frontier in CAR T-cell therapy is figuring out which patients will respond well to CAR T and which are going to need more treatment after CAR T. However, he noted that evidence suggests patients with low MRD are likely to do best on CAR T and that bispecific antibodies can help patients get to what might be the best chance at a cure for r/r ALL, namely CAR-T.
The moderator of the debate, Jessica Altman, MD, professor of medicine, hematology oncology division, Feinberg School of Medicine at Northwestern University in Chicago, noted: “My take home is that antibody therapy and CAR-T will be sequenced and used together.” She noted that blinatumomab is moving into the front line of therapy, as in the E1910 trials, and how this treatment allows for study and use of CAR T earlier in the care of patients “when there may be less toxicity and higher response.”
Jabbour concluded on a similar note, adding that the “cure for this disease will happen in our lifetime. We will shorten therapy by doing immunotherapy upfront followed by CAR T consolidation and no more transplantation. I don’t think antibodies immunotherapies or CAR T need be competitive, they can be used in a complimentary fashion.”
Jabbour reported no financial disclosures. Park disclosed ties with Allogene, Artiva Biotherapeutics, Amgen, Affyimmune, BeBiopharma, Beigene, Bright Pharmaceuticals, Autolus, Caribou Biosciences, Galapagos, Kite, Medpace, Minerva Biotechnologies, Pfizer, Servier, Sobi, and Takeda. Neither Altman nor Shastri reported any disclosures.
The comparative benefits and limitations of these two treatments for r/r ALL were a topic for discussion at the Great Debates & Updates Hematological Malignancies conference, held April 5-6 in New York City.
“Every single patient with ALL should benefit from bispecific antibodies before getting CAR-T cells, and I want to make the case that everybody should get CAR T as well. But they should get blinatumomab before they get CAR T,” said Elias Jabbour, MD, of the MD Anderson Cancer Center at The University of Texas in Houston, whose presentation focused on the merits of bispecific antibodies.
His argument was based on data indicating that patients have better chances of long-term remission with the use of bispecific antibodies when they are administered in an earlier round of salvage treatment — and the fact that patients who are not cured with these drugs can still achieve a lower disease burden and perform better on CAR T-cell therapy than those who don’t receive the drugs.
“When blinatumomab is used as a consolidation during the first salvage treatment and spaces out transplantation, 3-year overall survival increases in the relapse setting, deepening responses and reducing the rate of VOD (veno-occlusive disease). The safety and efficacy of CAR T depends on a disease burden. If you have a minimal residual disease (MRD), you have a safer outcome and a better outcome in the long run,” Dr. Jabbour explained.
This point of view is supported by data from the treatment of patients r/r ALL with low intensity chemotherapy + inotuzumab ozogamicin (Besponsa; Pfizer) +/- blinatumomab (Blincyto; Amgen), knows as Mini-HCVD + Ino +/-Blina. Trial members achieved a median overall survival (OS) rate of 17 months, a 3-year survival rate of 42%, and an overall MRD negativity rate of 85%.
Dr. Jabbour noted that blinatumomab has its limitations. Generally, this treatment is administered intravenously every few weeks and can be cumbersome for patients who must travel to an infusion center. However, data from a phase 1b trial of single agent subcutaneous blinatumomab for advanced ALL has demonstrated that this formulation can be effective and can lead to MRD negativity, possibly paving the way for easier administration of the drug.
Aditi Shastri, MD, a leukemia specialist at New York’s Montefiore Medical Center who attended the debate, agreed that the data presented did support Dr. Jabbour’s contention that subcutaneous blinatumomab could make treatment available to even more people with r/r ALL. “It’s easier to administer than the blina pump and could act as a bridge to curative therapies like AlloHSCT,” she said.
Jae Park, MD, a leukemia and cellular therapy specialist at Memorial Sloan Kettering Cancer Center in New York City, argued that CAR T is the most potent therapy for r/r ALL. Dr. Park agreed that inotuzumab and blinatumomab have yielded tremendous progress in the treatment of patients with r/r ALL, but he noted that bispecific antibodies lack some of the advantages of CAR T.
Dr. Park said that the biggest difference between the two therapies is that CAR T requires but a single infusion of a living drug. Patients do need to stay close to treatment centers to receive treatment for toxicities, but after about 28 days, they can go home and be monitored from a distance. Furthermore, patients may start by receiving 1 million T-cells, but those cells exponentially expand 100,000- to 1,000,000-fold, meaning that the T-cells to treat cancer have the potential to persist for months and sometimes years.
Furthermore, results from ZUMA-3 Trial of the CD19-targeting CAR T-Cell therapy brexucabtagene autoleucel (Tecartus; Kite Pharma) suggest that CAR T outperforms Mini-HCVD + Ino +/-Blina in patients with r/r ALL. Participants in the trial showed an overall response rate around 80%, a 71% complete response rate, and a median OS of 25.4 months. Patients who achieved a complete response had an even better median OS of 47 months. Although this was not a head-to-head trial with Mini-HCVD + Ino +/-Blina, if the plateau of long-term survivors continues, “this drug could be set apart from treatment with monoclonal antibodies,” Dr. Park said.
However, brexucabtagene autoleucel is not a cure or even an option for all patients. Some patients are too frail to get the drug, and they risk experiencing cytokine release syndrome (CRS). Data from the FELIX study suggest that the CAR T-cell treatment Obe-cel could offer a safety profile that reduces the risk of serious side effects while remaining effective at treating r/r ALL. Obe-cel showed efficacy very similar to that of brexucabtagene autoleucel, with a 70%-80% response rate, and only 2% of patients experienced CRS.
Dr. Park noted that the next frontier in CAR T-cell therapy is figuring out which patients will respond well to CAR T and which are going to need more treatment after CAR T. However, he noted that evidence suggests patients with low MRD are likely to do best on CAR T and that bispecific antibodies can help patients get to what might be the best chance at a cure for r/r ALL, namely CAR-T.
The moderator of the debate, Jessica Altman, MD, professor of medicine, hematology oncology division, Feinberg School of Medicine at Northwestern University in Chicago, noted: “My take home is that antibody therapy and CAR-T will be sequenced and used together.” She noted that blinatumomab is moving into the front line of therapy, as in the E1910 trials, and how this treatment allows for study and use of CAR T earlier in the care of patients “when there may be less toxicity and higher response.”
Jabbour concluded on a similar note, adding that the “cure for this disease will happen in our lifetime. We will shorten therapy by doing immunotherapy upfront followed by CAR T consolidation and no more transplantation. I don’t think antibodies immunotherapies or CAR T need be competitive, they can be used in a complimentary fashion.”
Jabbour reported no financial disclosures. Park disclosed ties with Allogene, Artiva Biotherapeutics, Amgen, Affyimmune, BeBiopharma, Beigene, Bright Pharmaceuticals, Autolus, Caribou Biosciences, Galapagos, Kite, Medpace, Minerva Biotechnologies, Pfizer, Servier, Sobi, and Takeda. Neither Altman nor Shastri reported any disclosures.
The comparative benefits and limitations of these two treatments for r/r ALL were a topic for discussion at the Great Debates & Updates Hematological Malignancies conference, held April 5-6 in New York City.
“Every single patient with ALL should benefit from bispecific antibodies before getting CAR-T cells, and I want to make the case that everybody should get CAR T as well. But they should get blinatumomab before they get CAR T,” said Elias Jabbour, MD, of the MD Anderson Cancer Center at The University of Texas in Houston, whose presentation focused on the merits of bispecific antibodies.
His argument was based on data indicating that patients have better chances of long-term remission with the use of bispecific antibodies when they are administered in an earlier round of salvage treatment — and the fact that patients who are not cured with these drugs can still achieve a lower disease burden and perform better on CAR T-cell therapy than those who don’t receive the drugs.
“When blinatumomab is used as a consolidation during the first salvage treatment and spaces out transplantation, 3-year overall survival increases in the relapse setting, deepening responses and reducing the rate of VOD (veno-occlusive disease). The safety and efficacy of CAR T depends on a disease burden. If you have a minimal residual disease (MRD), you have a safer outcome and a better outcome in the long run,” Dr. Jabbour explained.
This point of view is supported by data from the treatment of patients r/r ALL with low intensity chemotherapy + inotuzumab ozogamicin (Besponsa; Pfizer) +/- blinatumomab (Blincyto; Amgen), knows as Mini-HCVD + Ino +/-Blina. Trial members achieved a median overall survival (OS) rate of 17 months, a 3-year survival rate of 42%, and an overall MRD negativity rate of 85%.
Dr. Jabbour noted that blinatumomab has its limitations. Generally, this treatment is administered intravenously every few weeks and can be cumbersome for patients who must travel to an infusion center. However, data from a phase 1b trial of single agent subcutaneous blinatumomab for advanced ALL has demonstrated that this formulation can be effective and can lead to MRD negativity, possibly paving the way for easier administration of the drug.
Aditi Shastri, MD, a leukemia specialist at New York’s Montefiore Medical Center who attended the debate, agreed that the data presented did support Dr. Jabbour’s contention that subcutaneous blinatumomab could make treatment available to even more people with r/r ALL. “It’s easier to administer than the blina pump and could act as a bridge to curative therapies like AlloHSCT,” she said.
Jae Park, MD, a leukemia and cellular therapy specialist at Memorial Sloan Kettering Cancer Center in New York City, argued that CAR T is the most potent therapy for r/r ALL. Dr. Park agreed that inotuzumab and blinatumomab have yielded tremendous progress in the treatment of patients with r/r ALL, but he noted that bispecific antibodies lack some of the advantages of CAR T.
Dr. Park said that the biggest difference between the two therapies is that CAR T requires but a single infusion of a living drug. Patients do need to stay close to treatment centers to receive treatment for toxicities, but after about 28 days, they can go home and be monitored from a distance. Furthermore, patients may start by receiving 1 million T-cells, but those cells exponentially expand 100,000- to 1,000,000-fold, meaning that the T-cells to treat cancer have the potential to persist for months and sometimes years.
Furthermore, results from ZUMA-3 Trial of the CD19-targeting CAR T-Cell therapy brexucabtagene autoleucel (Tecartus; Kite Pharma) suggest that CAR T outperforms Mini-HCVD + Ino +/-Blina in patients with r/r ALL. Participants in the trial showed an overall response rate around 80%, a 71% complete response rate, and a median OS of 25.4 months. Patients who achieved a complete response had an even better median OS of 47 months. Although this was not a head-to-head trial with Mini-HCVD + Ino +/-Blina, if the plateau of long-term survivors continues, “this drug could be set apart from treatment with monoclonal antibodies,” Dr. Park said.
However, brexucabtagene autoleucel is not a cure or even an option for all patients. Some patients are too frail to get the drug, and they risk experiencing cytokine release syndrome (CRS). Data from the FELIX study suggest that the CAR T-cell treatment Obe-cel could offer a safety profile that reduces the risk of serious side effects while remaining effective at treating r/r ALL. Obe-cel showed efficacy very similar to that of brexucabtagene autoleucel, with a 70%-80% response rate, and only 2% of patients experienced CRS.
Dr. Park noted that the next frontier in CAR T-cell therapy is figuring out which patients will respond well to CAR T and which are going to need more treatment after CAR T. However, he noted that evidence suggests patients with low MRD are likely to do best on CAR T and that bispecific antibodies can help patients get to what might be the best chance at a cure for r/r ALL, namely CAR-T.
The moderator of the debate, Jessica Altman, MD, professor of medicine, hematology oncology division, Feinberg School of Medicine at Northwestern University in Chicago, noted: “My take home is that antibody therapy and CAR-T will be sequenced and used together.” She noted that blinatumomab is moving into the front line of therapy, as in the E1910 trials, and how this treatment allows for study and use of CAR T earlier in the care of patients “when there may be less toxicity and higher response.”
Jabbour concluded on a similar note, adding that the “cure for this disease will happen in our lifetime. We will shorten therapy by doing immunotherapy upfront followed by CAR T consolidation and no more transplantation. I don’t think antibodies immunotherapies or CAR T need be competitive, they can be used in a complimentary fashion.”
Jabbour reported no financial disclosures. Park disclosed ties with Allogene, Artiva Biotherapeutics, Amgen, Affyimmune, BeBiopharma, Beigene, Bright Pharmaceuticals, Autolus, Caribou Biosciences, Galapagos, Kite, Medpace, Minerva Biotechnologies, Pfizer, Servier, Sobi, and Takeda. Neither Altman nor Shastri reported any disclosures.
FROM GREAT DEBATES & UPDATES HEMATOLOGIC MALIGNANCIES
First US Adult ADHD Guidelines Finally on the Way?
The first US clinical guidelines to diagnose and treat attention-deficit/hyperactivity disorder (ADHD) in adults are expected to be released this fall, providing patients, clinicians, insurers, and policymakers with a long overdue and much-needed standardized framework.
The initiative comes under the auspices of the American Professional Society of ADHD and Related Disorders (APSARD). David Goodman, MD, a member of the APSARD guidelines executive committee and assistant professor in the Department of Psychiatry and Behavioral Sciences at Johns Hopkins School of Medicine in Baltimore, Maryland, noted that the US lags behind several other nations, including Canada, the United Kingdom, Australia, and New Zealand who already have guidelines in place.
Dr. Goodman would not go into any detail as to why the country has been so slow off the mark but told this news organization that in part it has been due to a lack of specific funding. In addition, he said, “adult psychiatry abdicated responsibility for ADHD in adults.”
The American Psychiatric Association (APA) would not comment, although a spokesperson said two of its members are working with APSARD on the guidelines.
Estimates show that there are 10-11 million American adults (4.4%) with ADHD, making it the second most common psychiatric disorder in adults.
Surveys show that mental health professionals, including psychiatrists, report a lack of familiarity with ADHD in adults, said Margaret Sibley, PhD, professor of psychiatry and behavioral sciences at the University of Washington School of Medicine in Seattle and chair of the APSARD guidelines diagnostic and screening committee.
Many don’t consider an ADHD diagnosis in adults “because they were always trained to conceptualize it as something that’s relevant only in childhood,” Dr. Sibley told this new organization. However, research shows that people with ADHD do not outgrow the disorder.
“ADHD itself is still present and has unique problems associated with it in adults,” Dr. Sibley said.
Filling the Leadership Gap
Laurie Kulikosky, CEO of the advocacy group CHADD, said that the organization views the development of guidelines “as a huge step forward in the ability for more people to understand ADHD, particularly on the adult side.”
Oren Mason, MD, a primary care physician who specializes in ADHD at his Grand Rapids, Michigan-based practice, said “there hasn’t been a single specialty that has taken lead responsibility in adult ADHD,” which has contributed to the lag in guideline development.
In addition, Dr. Mason said, “trying to come up with adult guidelines even 5 or 10 years ago wouldn’t have yielded nearly as robust a set of guidelines because it’s taken awhile to have the evidence base to be able to make a few pronouncements really confidently.”
Not only has the evidence base grown but so has telehealth, especially during the height of the COVID-19 pandemic. That led to concerns that ADHD was not rigorously evaluated and that stimulants were prescribed too easily, said Dr. Goodman.
Several telehealth providers came under federal scrutiny, with the DEA accusing Cerebral’s pharmacy of dispensing stimulants for nonmedical reasons. The agency said that some 72,000 prescriptions for controlled substances, mostly stimulants, were written between 2020 and 2022.
APSARD felt it was time to act, said Dr. Goodman.
“We could not allow entrepreneurs who felt there was a business opportunity here to, under the auspices of advocating for mental health, increase the distribution of potentially addictive medications in the community,” he said
Ensuring Psychiatrist Buy-In
Development of the APSARD guidelines is led by Thomas Spencer, MD, a retired associate professor of psychiatry at Harvard Medical School, and Frances Rudnick Levin, MD, the Kennedy-Leavy Professor of Psychiatry at Columbia University, both of whom have decades of experience and clinical work in adults with ADHD.
Dr. Goodman is joined on the executive committee by Lenard Adler, MD (NYU Grossman School of Medicine), and Stephen Faraone, PhD (SUNY Upstate Medical University), along with 30 others who have expertise in psychiatry, psychology, primary care, and other health professions.
To participate in the development of the guidelines, experts had to agree to disengage from any potential conflicts and devote themselves — unpaid — to the process, said Dr. Goodman. The goal is to head off any charges of conflicts or biases, he said.
Three subcommittees — diagnosis and assessment, medical treatment, and nonmedical treatment — will review the literature, grade the evidence base, and use the Delphi consensus method to write the draft guidelines.
The draft will go out to the public and to medical specialties for comment, which will be considered for inclusion in the final publication, said Dr. Goodman.
The guidelines panel has been working closely with the APA and following the APA guideline development process in an effort to get buy-in from psychiatrists, he said.
Critical Educational Tool
“Doctors are often surprised to hear that there are no guidelines for adult ADHD in the US,” said Ann Childress, MD, APSARD president, when the group announced its effort in 2023. “Whether diagnosis and treatment are provided in office or online, the standard of care should be the same throughout the country,” she said.
Guidelines will “reduce mythology and error or at least when we run into mythology and error we can say no, there’s a giant consensus with hundreds of experts that disagree with that and so if you want to counter that you better bring some heavy machinery, you can’t just throw out an opinion and leave it unsupported,” said Dr. Mason.
Dr. Sibley said that, although there are no good data, anecdotally it appears many clinicians rely on the Diagnostic and Statistical Manual of Mental Disorders (DSM) when treating adults with ADHD.
The DSM “tells people what they should do but it doesn’t exactly tell them what’s the best way to do it,” she said, adding that often physicians follow what they learned from whoever they were trained by.
“Some people have been trained by people who are well versed in best practices and so they might be doing things that we would say have a research support to them, and other people might be doing things based on people who developed their own opinions about the best way to diagnose ADHD based on lived experience which may or may not be best practices,” Dr. Sibley said.
Her subcommittee aims to offer guidance on screening “that will be helpful in primary care, in terms of what are the most efficient ways to do it” and to help with accuracy, she said. Currently, there are likely some clinicians who are making too liberal a diagnosis and others who are making too conservative a diagnosis, she said.
With so many clinicians — especially in primary care — having a lack of experience, the guidelines could increase “the ability for more different kinds of providers to help,” said Dr. Kulikosky.
Guidelines should also provide a template for ongoing education, especially for clinicians who have never received any training in ADHD.
Dr. Goodman said it is increasingly likely that primary care physicians will be writing more prescriptions for ADHD medications than psychiatrists. “If that is the trajectory, the education of those providers seeing these patients is critical,” he said.
Offering Standards, Dispelling Myths
Guidelines can also help “shorten the learning curve,” said Dr. Mason, who said that he’s had to piece together evidence over the last few decades. Once published, the standards can be used in residency, for board exams, and continuing medical education, he said.
Not only do they offer a “kind of a shortcut to what we all know and agree on,” they also specify where the edges of knowledge are, he said.
Guidelines can also dissuade clinicians from practices that have no evidence to support them, such as “medication holidays,” said Dr. Mason. That has been employed to give children, especially, a break from side effects, but studies have shown that it actually increases side effects, he said.
Dr. Goodman and Dr. Sibley expect the guidelines to help with the challenge of diagnosis. Approximately 38% of adults with ADHD have a mood disorder and 48% have anxiety, said Dr. Goodman. Many others have coexisting posttraumatic stress disorder, substance use disorders, or medical illnesses that compound cognitive problems.
If an individual has several psychiatric conditions, “the question is how do you diagnostically prioritize which you treat first, second, and third, with the goal of treating one without making the others worse,” said Dr. Goodman.
“ADHD takes more detective work than other disorders,” said Dr. Sibley, adding that without an objective diagnostic and with overlaps with other comorbid disorders, “there are very complex issues that all of us wrestle with.”
While the guidelines will not provide algorithms, they will provide information that “will help guide them in the tougher diagnostic context,” she said.
Dr. Mason agreed. “It’s a complicated disorder to diagnose and treat. It’s hard for somebody to jump into it. [The guidelines] are going to give us — here’s what you really have to know, here’s what you have to do,” he said.
And it won’t just be clinicians who look to the guidelines. Calls to National Resource Center on ADHD — which CHADD runs for the federal government — from adults wanting to know more about their own condition “have increased exponentially” in the last few years, said Dr. Kulikosky. “We know adults are seeking out information, they are seeking out diagnosis and treatment,” she said.
Dr. Goodman and Dr. Sibley reported no relevant financial relationships. Dr. Mason reported that he consults for Otsuka and is a speaker for Iron Shore.
A version of this article first appeared on Medscape.com.
The first US clinical guidelines to diagnose and treat attention-deficit/hyperactivity disorder (ADHD) in adults are expected to be released this fall, providing patients, clinicians, insurers, and policymakers with a long overdue and much-needed standardized framework.
The initiative comes under the auspices of the American Professional Society of ADHD and Related Disorders (APSARD). David Goodman, MD, a member of the APSARD guidelines executive committee and assistant professor in the Department of Psychiatry and Behavioral Sciences at Johns Hopkins School of Medicine in Baltimore, Maryland, noted that the US lags behind several other nations, including Canada, the United Kingdom, Australia, and New Zealand who already have guidelines in place.
Dr. Goodman would not go into any detail as to why the country has been so slow off the mark but told this news organization that in part it has been due to a lack of specific funding. In addition, he said, “adult psychiatry abdicated responsibility for ADHD in adults.”
The American Psychiatric Association (APA) would not comment, although a spokesperson said two of its members are working with APSARD on the guidelines.
Estimates show that there are 10-11 million American adults (4.4%) with ADHD, making it the second most common psychiatric disorder in adults.
Surveys show that mental health professionals, including psychiatrists, report a lack of familiarity with ADHD in adults, said Margaret Sibley, PhD, professor of psychiatry and behavioral sciences at the University of Washington School of Medicine in Seattle and chair of the APSARD guidelines diagnostic and screening committee.
Many don’t consider an ADHD diagnosis in adults “because they were always trained to conceptualize it as something that’s relevant only in childhood,” Dr. Sibley told this new organization. However, research shows that people with ADHD do not outgrow the disorder.
“ADHD itself is still present and has unique problems associated with it in adults,” Dr. Sibley said.
Filling the Leadership Gap
Laurie Kulikosky, CEO of the advocacy group CHADD, said that the organization views the development of guidelines “as a huge step forward in the ability for more people to understand ADHD, particularly on the adult side.”
Oren Mason, MD, a primary care physician who specializes in ADHD at his Grand Rapids, Michigan-based practice, said “there hasn’t been a single specialty that has taken lead responsibility in adult ADHD,” which has contributed to the lag in guideline development.
In addition, Dr. Mason said, “trying to come up with adult guidelines even 5 or 10 years ago wouldn’t have yielded nearly as robust a set of guidelines because it’s taken awhile to have the evidence base to be able to make a few pronouncements really confidently.”
Not only has the evidence base grown but so has telehealth, especially during the height of the COVID-19 pandemic. That led to concerns that ADHD was not rigorously evaluated and that stimulants were prescribed too easily, said Dr. Goodman.
Several telehealth providers came under federal scrutiny, with the DEA accusing Cerebral’s pharmacy of dispensing stimulants for nonmedical reasons. The agency said that some 72,000 prescriptions for controlled substances, mostly stimulants, were written between 2020 and 2022.
APSARD felt it was time to act, said Dr. Goodman.
“We could not allow entrepreneurs who felt there was a business opportunity here to, under the auspices of advocating for mental health, increase the distribution of potentially addictive medications in the community,” he said
Ensuring Psychiatrist Buy-In
Development of the APSARD guidelines is led by Thomas Spencer, MD, a retired associate professor of psychiatry at Harvard Medical School, and Frances Rudnick Levin, MD, the Kennedy-Leavy Professor of Psychiatry at Columbia University, both of whom have decades of experience and clinical work in adults with ADHD.
Dr. Goodman is joined on the executive committee by Lenard Adler, MD (NYU Grossman School of Medicine), and Stephen Faraone, PhD (SUNY Upstate Medical University), along with 30 others who have expertise in psychiatry, psychology, primary care, and other health professions.
To participate in the development of the guidelines, experts had to agree to disengage from any potential conflicts and devote themselves — unpaid — to the process, said Dr. Goodman. The goal is to head off any charges of conflicts or biases, he said.
Three subcommittees — diagnosis and assessment, medical treatment, and nonmedical treatment — will review the literature, grade the evidence base, and use the Delphi consensus method to write the draft guidelines.
The draft will go out to the public and to medical specialties for comment, which will be considered for inclusion in the final publication, said Dr. Goodman.
The guidelines panel has been working closely with the APA and following the APA guideline development process in an effort to get buy-in from psychiatrists, he said.
Critical Educational Tool
“Doctors are often surprised to hear that there are no guidelines for adult ADHD in the US,” said Ann Childress, MD, APSARD president, when the group announced its effort in 2023. “Whether diagnosis and treatment are provided in office or online, the standard of care should be the same throughout the country,” she said.
Guidelines will “reduce mythology and error or at least when we run into mythology and error we can say no, there’s a giant consensus with hundreds of experts that disagree with that and so if you want to counter that you better bring some heavy machinery, you can’t just throw out an opinion and leave it unsupported,” said Dr. Mason.
Dr. Sibley said that, although there are no good data, anecdotally it appears many clinicians rely on the Diagnostic and Statistical Manual of Mental Disorders (DSM) when treating adults with ADHD.
The DSM “tells people what they should do but it doesn’t exactly tell them what’s the best way to do it,” she said, adding that often physicians follow what they learned from whoever they were trained by.
“Some people have been trained by people who are well versed in best practices and so they might be doing things that we would say have a research support to them, and other people might be doing things based on people who developed their own opinions about the best way to diagnose ADHD based on lived experience which may or may not be best practices,” Dr. Sibley said.
Her subcommittee aims to offer guidance on screening “that will be helpful in primary care, in terms of what are the most efficient ways to do it” and to help with accuracy, she said. Currently, there are likely some clinicians who are making too liberal a diagnosis and others who are making too conservative a diagnosis, she said.
With so many clinicians — especially in primary care — having a lack of experience, the guidelines could increase “the ability for more different kinds of providers to help,” said Dr. Kulikosky.
Guidelines should also provide a template for ongoing education, especially for clinicians who have never received any training in ADHD.
Dr. Goodman said it is increasingly likely that primary care physicians will be writing more prescriptions for ADHD medications than psychiatrists. “If that is the trajectory, the education of those providers seeing these patients is critical,” he said.
Offering Standards, Dispelling Myths
Guidelines can also help “shorten the learning curve,” said Dr. Mason, who said that he’s had to piece together evidence over the last few decades. Once published, the standards can be used in residency, for board exams, and continuing medical education, he said.
Not only do they offer a “kind of a shortcut to what we all know and agree on,” they also specify where the edges of knowledge are, he said.
Guidelines can also dissuade clinicians from practices that have no evidence to support them, such as “medication holidays,” said Dr. Mason. That has been employed to give children, especially, a break from side effects, but studies have shown that it actually increases side effects, he said.
Dr. Goodman and Dr. Sibley expect the guidelines to help with the challenge of diagnosis. Approximately 38% of adults with ADHD have a mood disorder and 48% have anxiety, said Dr. Goodman. Many others have coexisting posttraumatic stress disorder, substance use disorders, or medical illnesses that compound cognitive problems.
If an individual has several psychiatric conditions, “the question is how do you diagnostically prioritize which you treat first, second, and third, with the goal of treating one without making the others worse,” said Dr. Goodman.
“ADHD takes more detective work than other disorders,” said Dr. Sibley, adding that without an objective diagnostic and with overlaps with other comorbid disorders, “there are very complex issues that all of us wrestle with.”
While the guidelines will not provide algorithms, they will provide information that “will help guide them in the tougher diagnostic context,” she said.
Dr. Mason agreed. “It’s a complicated disorder to diagnose and treat. It’s hard for somebody to jump into it. [The guidelines] are going to give us — here’s what you really have to know, here’s what you have to do,” he said.
And it won’t just be clinicians who look to the guidelines. Calls to National Resource Center on ADHD — which CHADD runs for the federal government — from adults wanting to know more about their own condition “have increased exponentially” in the last few years, said Dr. Kulikosky. “We know adults are seeking out information, they are seeking out diagnosis and treatment,” she said.
Dr. Goodman and Dr. Sibley reported no relevant financial relationships. Dr. Mason reported that he consults for Otsuka and is a speaker for Iron Shore.
A version of this article first appeared on Medscape.com.
The first US clinical guidelines to diagnose and treat attention-deficit/hyperactivity disorder (ADHD) in adults are expected to be released this fall, providing patients, clinicians, insurers, and policymakers with a long overdue and much-needed standardized framework.
The initiative comes under the auspices of the American Professional Society of ADHD and Related Disorders (APSARD). David Goodman, MD, a member of the APSARD guidelines executive committee and assistant professor in the Department of Psychiatry and Behavioral Sciences at Johns Hopkins School of Medicine in Baltimore, Maryland, noted that the US lags behind several other nations, including Canada, the United Kingdom, Australia, and New Zealand who already have guidelines in place.
Dr. Goodman would not go into any detail as to why the country has been so slow off the mark but told this news organization that in part it has been due to a lack of specific funding. In addition, he said, “adult psychiatry abdicated responsibility for ADHD in adults.”
The American Psychiatric Association (APA) would not comment, although a spokesperson said two of its members are working with APSARD on the guidelines.
Estimates show that there are 10-11 million American adults (4.4%) with ADHD, making it the second most common psychiatric disorder in adults.
Surveys show that mental health professionals, including psychiatrists, report a lack of familiarity with ADHD in adults, said Margaret Sibley, PhD, professor of psychiatry and behavioral sciences at the University of Washington School of Medicine in Seattle and chair of the APSARD guidelines diagnostic and screening committee.
Many don’t consider an ADHD diagnosis in adults “because they were always trained to conceptualize it as something that’s relevant only in childhood,” Dr. Sibley told this new organization. However, research shows that people with ADHD do not outgrow the disorder.
“ADHD itself is still present and has unique problems associated with it in adults,” Dr. Sibley said.
Filling the Leadership Gap
Laurie Kulikosky, CEO of the advocacy group CHADD, said that the organization views the development of guidelines “as a huge step forward in the ability for more people to understand ADHD, particularly on the adult side.”
Oren Mason, MD, a primary care physician who specializes in ADHD at his Grand Rapids, Michigan-based practice, said “there hasn’t been a single specialty that has taken lead responsibility in adult ADHD,” which has contributed to the lag in guideline development.
In addition, Dr. Mason said, “trying to come up with adult guidelines even 5 or 10 years ago wouldn’t have yielded nearly as robust a set of guidelines because it’s taken awhile to have the evidence base to be able to make a few pronouncements really confidently.”
Not only has the evidence base grown but so has telehealth, especially during the height of the COVID-19 pandemic. That led to concerns that ADHD was not rigorously evaluated and that stimulants were prescribed too easily, said Dr. Goodman.
Several telehealth providers came under federal scrutiny, with the DEA accusing Cerebral’s pharmacy of dispensing stimulants for nonmedical reasons. The agency said that some 72,000 prescriptions for controlled substances, mostly stimulants, were written between 2020 and 2022.
APSARD felt it was time to act, said Dr. Goodman.
“We could not allow entrepreneurs who felt there was a business opportunity here to, under the auspices of advocating for mental health, increase the distribution of potentially addictive medications in the community,” he said
Ensuring Psychiatrist Buy-In
Development of the APSARD guidelines is led by Thomas Spencer, MD, a retired associate professor of psychiatry at Harvard Medical School, and Frances Rudnick Levin, MD, the Kennedy-Leavy Professor of Psychiatry at Columbia University, both of whom have decades of experience and clinical work in adults with ADHD.
Dr. Goodman is joined on the executive committee by Lenard Adler, MD (NYU Grossman School of Medicine), and Stephen Faraone, PhD (SUNY Upstate Medical University), along with 30 others who have expertise in psychiatry, psychology, primary care, and other health professions.
To participate in the development of the guidelines, experts had to agree to disengage from any potential conflicts and devote themselves — unpaid — to the process, said Dr. Goodman. The goal is to head off any charges of conflicts or biases, he said.
Three subcommittees — diagnosis and assessment, medical treatment, and nonmedical treatment — will review the literature, grade the evidence base, and use the Delphi consensus method to write the draft guidelines.
The draft will go out to the public and to medical specialties for comment, which will be considered for inclusion in the final publication, said Dr. Goodman.
The guidelines panel has been working closely with the APA and following the APA guideline development process in an effort to get buy-in from psychiatrists, he said.
Critical Educational Tool
“Doctors are often surprised to hear that there are no guidelines for adult ADHD in the US,” said Ann Childress, MD, APSARD president, when the group announced its effort in 2023. “Whether diagnosis and treatment are provided in office or online, the standard of care should be the same throughout the country,” she said.
Guidelines will “reduce mythology and error or at least when we run into mythology and error we can say no, there’s a giant consensus with hundreds of experts that disagree with that and so if you want to counter that you better bring some heavy machinery, you can’t just throw out an opinion and leave it unsupported,” said Dr. Mason.
Dr. Sibley said that, although there are no good data, anecdotally it appears many clinicians rely on the Diagnostic and Statistical Manual of Mental Disorders (DSM) when treating adults with ADHD.
The DSM “tells people what they should do but it doesn’t exactly tell them what’s the best way to do it,” she said, adding that often physicians follow what they learned from whoever they were trained by.
“Some people have been trained by people who are well versed in best practices and so they might be doing things that we would say have a research support to them, and other people might be doing things based on people who developed their own opinions about the best way to diagnose ADHD based on lived experience which may or may not be best practices,” Dr. Sibley said.
Her subcommittee aims to offer guidance on screening “that will be helpful in primary care, in terms of what are the most efficient ways to do it” and to help with accuracy, she said. Currently, there are likely some clinicians who are making too liberal a diagnosis and others who are making too conservative a diagnosis, she said.
With so many clinicians — especially in primary care — having a lack of experience, the guidelines could increase “the ability for more different kinds of providers to help,” said Dr. Kulikosky.
Guidelines should also provide a template for ongoing education, especially for clinicians who have never received any training in ADHD.
Dr. Goodman said it is increasingly likely that primary care physicians will be writing more prescriptions for ADHD medications than psychiatrists. “If that is the trajectory, the education of those providers seeing these patients is critical,” he said.
Offering Standards, Dispelling Myths
Guidelines can also help “shorten the learning curve,” said Dr. Mason, who said that he’s had to piece together evidence over the last few decades. Once published, the standards can be used in residency, for board exams, and continuing medical education, he said.
Not only do they offer a “kind of a shortcut to what we all know and agree on,” they also specify where the edges of knowledge are, he said.
Guidelines can also dissuade clinicians from practices that have no evidence to support them, such as “medication holidays,” said Dr. Mason. That has been employed to give children, especially, a break from side effects, but studies have shown that it actually increases side effects, he said.
Dr. Goodman and Dr. Sibley expect the guidelines to help with the challenge of diagnosis. Approximately 38% of adults with ADHD have a mood disorder and 48% have anxiety, said Dr. Goodman. Many others have coexisting posttraumatic stress disorder, substance use disorders, or medical illnesses that compound cognitive problems.
If an individual has several psychiatric conditions, “the question is how do you diagnostically prioritize which you treat first, second, and third, with the goal of treating one without making the others worse,” said Dr. Goodman.
“ADHD takes more detective work than other disorders,” said Dr. Sibley, adding that without an objective diagnostic and with overlaps with other comorbid disorders, “there are very complex issues that all of us wrestle with.”
While the guidelines will not provide algorithms, they will provide information that “will help guide them in the tougher diagnostic context,” she said.
Dr. Mason agreed. “It’s a complicated disorder to diagnose and treat. It’s hard for somebody to jump into it. [The guidelines] are going to give us — here’s what you really have to know, here’s what you have to do,” he said.
And it won’t just be clinicians who look to the guidelines. Calls to National Resource Center on ADHD — which CHADD runs for the federal government — from adults wanting to know more about their own condition “have increased exponentially” in the last few years, said Dr. Kulikosky. “We know adults are seeking out information, they are seeking out diagnosis and treatment,” she said.
Dr. Goodman and Dr. Sibley reported no relevant financial relationships. Dr. Mason reported that he consults for Otsuka and is a speaker for Iron Shore.
A version of this article first appeared on Medscape.com.
High Infection Risk in Rheumatoid Arthritis–Associated Interstitial Lung Disease
TOPLINE:
METHODOLOGY:
- Patients with RA who have extra-articular manifestations such as ILD are highly susceptible to infections, but information on the types of infections, risk factors, and associations of infections with hospitalization and mortality is limited.
- This prospective multicenter cohort study evaluated infections in a cohort of 148 patients with RA-ILD (average age, 70 years; 57% women) recruited from 11 university hospitals in Spain between March 2015 and March 2023.
- Joint, lung, and any infection-related variables were evaluated using clinical and laboratory evaluations at baseline and selected time points till the end of the follow-up period (mean, 56.7 months).
- Researchers also investigated the common infectious sites, the etiology of the infection, vaccination status, variables associated with lung function, and clinical-therapeutic variables associated with RA.
TAKEAWAY:
- During the follow-up period, almost all (96%) patients had at least one infection, with the median time to first infection being 21.2 months and 65% of the deaths being directly related to infections.
- Respiratory infections were the most common first infections (74%) and led to death in 80% of the patients. Urinary tract (9.9%) and skin and soft tissue (9.1%) infections were the second and third most common first infections, respectively.
- Most infections were caused by SARS-CoV-2 (33.5%), Streptococcus pneumoniae (11.9%), Escherichia coli (11.9%), and Pseudomonas aeruginosa (11.1%), with mortality at 25.8% for SARS-CoV-2, 12.9% for P aeruginosa (12.9%), and 9.6% for pneumococci (9.6%).
- Increased age, disease activity, and the use of corticosteroids were associated with an elevated risk for infection and mortality in patients with RA-ILD.
IN PRACTICE:
“Our results demonstrate a high occurrence of serious infections among these patients, occurring early, recurring frequently, and proving fatal in 65% of cases,” the authors wrote.
SOURCE:
This study was led by Natalia Mena-Vázquez, MD, PhD, from Instituto de Investigación Biomédica de Málaga-Plataforma Bionand, Málaga, Spain, and published online March 27 in Frontiers in Immunology.
LIMITATIONS:
The findings of this study have been affected by the COVID-19 pandemic. The lack of a control group also limited the ability of this study to establish any causal relationships between ILD and the clinical outcomes analyzed.
DISCLOSURE:
This study was supported by Redes de Investigación Cooperativa Orientadas a Resultados en Salud and Fundación Andaluza de Reumatología. The authors declared having no conflicts of interest.
A version of this article appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- Patients with RA who have extra-articular manifestations such as ILD are highly susceptible to infections, but information on the types of infections, risk factors, and associations of infections with hospitalization and mortality is limited.
- This prospective multicenter cohort study evaluated infections in a cohort of 148 patients with RA-ILD (average age, 70 years; 57% women) recruited from 11 university hospitals in Spain between March 2015 and March 2023.
- Joint, lung, and any infection-related variables were evaluated using clinical and laboratory evaluations at baseline and selected time points till the end of the follow-up period (mean, 56.7 months).
- Researchers also investigated the common infectious sites, the etiology of the infection, vaccination status, variables associated with lung function, and clinical-therapeutic variables associated with RA.
TAKEAWAY:
- During the follow-up period, almost all (96%) patients had at least one infection, with the median time to first infection being 21.2 months and 65% of the deaths being directly related to infections.
- Respiratory infections were the most common first infections (74%) and led to death in 80% of the patients. Urinary tract (9.9%) and skin and soft tissue (9.1%) infections were the second and third most common first infections, respectively.
- Most infections were caused by SARS-CoV-2 (33.5%), Streptococcus pneumoniae (11.9%), Escherichia coli (11.9%), and Pseudomonas aeruginosa (11.1%), with mortality at 25.8% for SARS-CoV-2, 12.9% for P aeruginosa (12.9%), and 9.6% for pneumococci (9.6%).
- Increased age, disease activity, and the use of corticosteroids were associated with an elevated risk for infection and mortality in patients with RA-ILD.
IN PRACTICE:
“Our results demonstrate a high occurrence of serious infections among these patients, occurring early, recurring frequently, and proving fatal in 65% of cases,” the authors wrote.
SOURCE:
This study was led by Natalia Mena-Vázquez, MD, PhD, from Instituto de Investigación Biomédica de Málaga-Plataforma Bionand, Málaga, Spain, and published online March 27 in Frontiers in Immunology.
LIMITATIONS:
The findings of this study have been affected by the COVID-19 pandemic. The lack of a control group also limited the ability of this study to establish any causal relationships between ILD and the clinical outcomes analyzed.
DISCLOSURE:
This study was supported by Redes de Investigación Cooperativa Orientadas a Resultados en Salud and Fundación Andaluza de Reumatología. The authors declared having no conflicts of interest.
A version of this article appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- Patients with RA who have extra-articular manifestations such as ILD are highly susceptible to infections, but information on the types of infections, risk factors, and associations of infections with hospitalization and mortality is limited.
- This prospective multicenter cohort study evaluated infections in a cohort of 148 patients with RA-ILD (average age, 70 years; 57% women) recruited from 11 university hospitals in Spain between March 2015 and March 2023.
- Joint, lung, and any infection-related variables were evaluated using clinical and laboratory evaluations at baseline and selected time points till the end of the follow-up period (mean, 56.7 months).
- Researchers also investigated the common infectious sites, the etiology of the infection, vaccination status, variables associated with lung function, and clinical-therapeutic variables associated with RA.
TAKEAWAY:
- During the follow-up period, almost all (96%) patients had at least one infection, with the median time to first infection being 21.2 months and 65% of the deaths being directly related to infections.
- Respiratory infections were the most common first infections (74%) and led to death in 80% of the patients. Urinary tract (9.9%) and skin and soft tissue (9.1%) infections were the second and third most common first infections, respectively.
- Most infections were caused by SARS-CoV-2 (33.5%), Streptococcus pneumoniae (11.9%), Escherichia coli (11.9%), and Pseudomonas aeruginosa (11.1%), with mortality at 25.8% for SARS-CoV-2, 12.9% for P aeruginosa (12.9%), and 9.6% for pneumococci (9.6%).
- Increased age, disease activity, and the use of corticosteroids were associated with an elevated risk for infection and mortality in patients with RA-ILD.
IN PRACTICE:
“Our results demonstrate a high occurrence of serious infections among these patients, occurring early, recurring frequently, and proving fatal in 65% of cases,” the authors wrote.
SOURCE:
This study was led by Natalia Mena-Vázquez, MD, PhD, from Instituto de Investigación Biomédica de Málaga-Plataforma Bionand, Málaga, Spain, and published online March 27 in Frontiers in Immunology.
LIMITATIONS:
The findings of this study have been affected by the COVID-19 pandemic. The lack of a control group also limited the ability of this study to establish any causal relationships between ILD and the clinical outcomes analyzed.
DISCLOSURE:
This study was supported by Redes de Investigación Cooperativa Orientadas a Resultados en Salud and Fundación Andaluza de Reumatología. The authors declared having no conflicts of interest.
A version of this article appeared on Medscape.com.
‘No Pulse’: An MD’s First Night Off in 2 Weeks Turns Grave
Emergencies happen anywhere, anytime, and sometimes, medical professionals find themselves in situations where they are the only ones who can help. Is There a Doctor in the House? is a series by this news organization that tells these stories.
It was my first night off after 12 days. It was a Friday night, and I went to a bar in Naples to get a beer with some friends. As it turned out, it wasn’t a night off after all.
As soon as we got inside, we heard over the speaker that they needed medical personnel and to please go to the left side of the bar. I thought it would be syncope or something like that.
I went over there and saw a woman holding up a man. He was basically leaning all over her. The light was low, and the music was pounding. I started to assess him and tried to get him to answer me. No response. I checked for pulses — nothing.
The woman helped me lower him to the floor. I checked again for a pulse. Still nothing. I said, “Call 911,” and started compressions.
The difficult part was the place was completely dark. I knew where his body was on the floor. I could see his chest. But I couldn’t see his face at all.
It was also extremely loud with the music thumping. After a while, they finally shut it off.
Pretty soon, the security personnel from the bar brought me an automated external defibrillator, and it showed the man was having V-fib arrest. I shocked him. Still no pulse. I continued with cardiopulmonary resuscitation (CPR).
I hadn’t noticed, but lots of people were crowding around us. Somebody came up and said, “He’s my friend. He has a 9-year-old daughter. He can’t die. Let me help with the compressions.” I was like, “Go for it.”
The guy started kind of pushing on the man’s abdomen. He had no idea how to do compressions. I said, “Okay, let me take over again.”
Out of the crowd, nobody else volunteered to help. No one asked me, “Hey, what can I do?” Meanwhile, I found out later that someone was filming the whole thing on their phone.
But what the guy said about the man’s young daughter stayed in my brain. I thought, we need to keep going.
I did more compressions and shocked him again. Still no pulse. At that point, the police and emergency medical services showed up. They checked, nothing had changed, so they got him into the ambulance.
I asked one of the paramedics, “Where are you taking him? I can call ahead.”
But he said, “That’s HIPAA. We can’t tell you.” They also wouldn’t let me go with him in the ambulance.
“I have an active Florida license, and I work in the ICU [intensive care unit],” I said.
“No, we need to follow our protocol,” he replied.
I understood that, but I just wanted to help.
It was around 10:30 PM by then, and I was drenched in sweat. I had to go home. The first thing I did after taking a shower was open the computer and check my system. I needed to find out what happened to the guy.
I was looking for admissions, and I didn’t see him. I called the main hospital downtown and the one in North Naples. I couldn’t find him anywhere. I stayed up until almost 1:00 AM checking for his name. At that point I thought, okay, maybe he died.
The next night, Saturday, I was home and got a call from one of my colleagues. “Hey, were you in a bar yesterday? Did you do CPR on somebody?”
“How did you know?” I said.
He said the paramedics had described me — “a tall doctor with glasses who was a nice guy.” It was funny that he knew that was me.
He told me, “The guy’s alive. He’s sick and needs to be put on dialysis, but he’s alive.”
Apparently, the guy had gone to the emergency department at North Naples, and the doctors in the emergency room (ER) worked on him for over an hour. They did continuous CPR and shocked him for close to 40 minutes. They finally got his pulse back, and after that, he was transferred to the main hospital ICU. They didn’t admit him at the ER, which was why I couldn’t find his name.
On Sunday, I was checking my patients’ charts for the ICU that coming week. And there he was. I saw his name and the documentation by the ED that CPR was provided by a critical care doctor in the field. He was still alive. That gave me so much joy.
So, the man I had helped became my patient. When I saw him on Monday, he was intubated and needed dialysis. I finally saw his face and thought, Oh, so that’s what you look like. I hadn’t realized he was only 39 years old.
When he was awake, I explained to him I was the doctor that provided CPR at the bar. He was very grateful, but of course, he didn’t remember anything.
Eventually, I met his daughter, and she just said, “Thank you for allowing me to have my dad.”
The funny part is that he broke his leg. Well, that’s not funny, but no one had any idea how it happened. That was his only complaint. He was asking me, “Doctor, how did you break my leg?”
“Hey, I have no idea how you broke your leg,” I replied. “I was trying to save your life.”
He was in the hospital for almost a month but made a full recovery. The amazing part: After all the evaluations, he has no neurological deficits. He’s back to a normal life now.
They never found a cause for the cardiac arrest. I mean, he had an ejection fraction of 10%. All my money was on something drug related, but that wasn’t the case. They’d done a cardiac cut, and there was no obstruction. They couldn’t find a reason.
We’ve become friends. He still works as a DJ at the bar. He changed his name to “DJ the Survivor” or something like that.
Sometimes, he’ll text me: “Doctor, what are you doing? You want to come down to the bar?”
I’m like, “No. I don’t.”
It’s been more than a year, but I remember every detail. When you go into medicine, you dream that one day you’ll be able to say, “I saved somebody.”
He texted me a year later and told me he’s celebrating two birthdays now. He said, “I’m turning 1 year old today!”
I think about the value of life. How we can take it for granted. We think, I’m young, nothing is going to happen to me. But this guy was 39. He went to work and died that night.
I was able to help bring him back. That makes me thankful for every day.
Jose Valle Giler, MD, is a pulmonary, critical care, and sleep medicine physician at NCH Healthcare System in Naples, Florida.
A version of this article appeared on Medscape.com .
Emergencies happen anywhere, anytime, and sometimes, medical professionals find themselves in situations where they are the only ones who can help. Is There a Doctor in the House? is a series by this news organization that tells these stories.
It was my first night off after 12 days. It was a Friday night, and I went to a bar in Naples to get a beer with some friends. As it turned out, it wasn’t a night off after all.
As soon as we got inside, we heard over the speaker that they needed medical personnel and to please go to the left side of the bar. I thought it would be syncope or something like that.
I went over there and saw a woman holding up a man. He was basically leaning all over her. The light was low, and the music was pounding. I started to assess him and tried to get him to answer me. No response. I checked for pulses — nothing.
The woman helped me lower him to the floor. I checked again for a pulse. Still nothing. I said, “Call 911,” and started compressions.
The difficult part was the place was completely dark. I knew where his body was on the floor. I could see his chest. But I couldn’t see his face at all.
It was also extremely loud with the music thumping. After a while, they finally shut it off.
Pretty soon, the security personnel from the bar brought me an automated external defibrillator, and it showed the man was having V-fib arrest. I shocked him. Still no pulse. I continued with cardiopulmonary resuscitation (CPR).
I hadn’t noticed, but lots of people were crowding around us. Somebody came up and said, “He’s my friend. He has a 9-year-old daughter. He can’t die. Let me help with the compressions.” I was like, “Go for it.”
The guy started kind of pushing on the man’s abdomen. He had no idea how to do compressions. I said, “Okay, let me take over again.”
Out of the crowd, nobody else volunteered to help. No one asked me, “Hey, what can I do?” Meanwhile, I found out later that someone was filming the whole thing on their phone.
But what the guy said about the man’s young daughter stayed in my brain. I thought, we need to keep going.
I did more compressions and shocked him again. Still no pulse. At that point, the police and emergency medical services showed up. They checked, nothing had changed, so they got him into the ambulance.
I asked one of the paramedics, “Where are you taking him? I can call ahead.”
But he said, “That’s HIPAA. We can’t tell you.” They also wouldn’t let me go with him in the ambulance.
“I have an active Florida license, and I work in the ICU [intensive care unit],” I said.
“No, we need to follow our protocol,” he replied.
I understood that, but I just wanted to help.
It was around 10:30 PM by then, and I was drenched in sweat. I had to go home. The first thing I did after taking a shower was open the computer and check my system. I needed to find out what happened to the guy.
I was looking for admissions, and I didn’t see him. I called the main hospital downtown and the one in North Naples. I couldn’t find him anywhere. I stayed up until almost 1:00 AM checking for his name. At that point I thought, okay, maybe he died.
The next night, Saturday, I was home and got a call from one of my colleagues. “Hey, were you in a bar yesterday? Did you do CPR on somebody?”
“How did you know?” I said.
He said the paramedics had described me — “a tall doctor with glasses who was a nice guy.” It was funny that he knew that was me.
He told me, “The guy’s alive. He’s sick and needs to be put on dialysis, but he’s alive.”
Apparently, the guy had gone to the emergency department at North Naples, and the doctors in the emergency room (ER) worked on him for over an hour. They did continuous CPR and shocked him for close to 40 minutes. They finally got his pulse back, and after that, he was transferred to the main hospital ICU. They didn’t admit him at the ER, which was why I couldn’t find his name.
On Sunday, I was checking my patients’ charts for the ICU that coming week. And there he was. I saw his name and the documentation by the ED that CPR was provided by a critical care doctor in the field. He was still alive. That gave me so much joy.
So, the man I had helped became my patient. When I saw him on Monday, he was intubated and needed dialysis. I finally saw his face and thought, Oh, so that’s what you look like. I hadn’t realized he was only 39 years old.
When he was awake, I explained to him I was the doctor that provided CPR at the bar. He was very grateful, but of course, he didn’t remember anything.
Eventually, I met his daughter, and she just said, “Thank you for allowing me to have my dad.”
The funny part is that he broke his leg. Well, that’s not funny, but no one had any idea how it happened. That was his only complaint. He was asking me, “Doctor, how did you break my leg?”
“Hey, I have no idea how you broke your leg,” I replied. “I was trying to save your life.”
He was in the hospital for almost a month but made a full recovery. The amazing part: After all the evaluations, he has no neurological deficits. He’s back to a normal life now.
They never found a cause for the cardiac arrest. I mean, he had an ejection fraction of 10%. All my money was on something drug related, but that wasn’t the case. They’d done a cardiac cut, and there was no obstruction. They couldn’t find a reason.
We’ve become friends. He still works as a DJ at the bar. He changed his name to “DJ the Survivor” or something like that.
Sometimes, he’ll text me: “Doctor, what are you doing? You want to come down to the bar?”
I’m like, “No. I don’t.”
It’s been more than a year, but I remember every detail. When you go into medicine, you dream that one day you’ll be able to say, “I saved somebody.”
He texted me a year later and told me he’s celebrating two birthdays now. He said, “I’m turning 1 year old today!”
I think about the value of life. How we can take it for granted. We think, I’m young, nothing is going to happen to me. But this guy was 39. He went to work and died that night.
I was able to help bring him back. That makes me thankful for every day.
Jose Valle Giler, MD, is a pulmonary, critical care, and sleep medicine physician at NCH Healthcare System in Naples, Florida.
A version of this article appeared on Medscape.com .
Emergencies happen anywhere, anytime, and sometimes, medical professionals find themselves in situations where they are the only ones who can help. Is There a Doctor in the House? is a series by this news organization that tells these stories.
It was my first night off after 12 days. It was a Friday night, and I went to a bar in Naples to get a beer with some friends. As it turned out, it wasn’t a night off after all.
As soon as we got inside, we heard over the speaker that they needed medical personnel and to please go to the left side of the bar. I thought it would be syncope or something like that.
I went over there and saw a woman holding up a man. He was basically leaning all over her. The light was low, and the music was pounding. I started to assess him and tried to get him to answer me. No response. I checked for pulses — nothing.
The woman helped me lower him to the floor. I checked again for a pulse. Still nothing. I said, “Call 911,” and started compressions.
The difficult part was the place was completely dark. I knew where his body was on the floor. I could see his chest. But I couldn’t see his face at all.
It was also extremely loud with the music thumping. After a while, they finally shut it off.
Pretty soon, the security personnel from the bar brought me an automated external defibrillator, and it showed the man was having V-fib arrest. I shocked him. Still no pulse. I continued with cardiopulmonary resuscitation (CPR).
I hadn’t noticed, but lots of people were crowding around us. Somebody came up and said, “He’s my friend. He has a 9-year-old daughter. He can’t die. Let me help with the compressions.” I was like, “Go for it.”
The guy started kind of pushing on the man’s abdomen. He had no idea how to do compressions. I said, “Okay, let me take over again.”
Out of the crowd, nobody else volunteered to help. No one asked me, “Hey, what can I do?” Meanwhile, I found out later that someone was filming the whole thing on their phone.
But what the guy said about the man’s young daughter stayed in my brain. I thought, we need to keep going.
I did more compressions and shocked him again. Still no pulse. At that point, the police and emergency medical services showed up. They checked, nothing had changed, so they got him into the ambulance.
I asked one of the paramedics, “Where are you taking him? I can call ahead.”
But he said, “That’s HIPAA. We can’t tell you.” They also wouldn’t let me go with him in the ambulance.
“I have an active Florida license, and I work in the ICU [intensive care unit],” I said.
“No, we need to follow our protocol,” he replied.
I understood that, but I just wanted to help.
It was around 10:30 PM by then, and I was drenched in sweat. I had to go home. The first thing I did after taking a shower was open the computer and check my system. I needed to find out what happened to the guy.
I was looking for admissions, and I didn’t see him. I called the main hospital downtown and the one in North Naples. I couldn’t find him anywhere. I stayed up until almost 1:00 AM checking for his name. At that point I thought, okay, maybe he died.
The next night, Saturday, I was home and got a call from one of my colleagues. “Hey, were you in a bar yesterday? Did you do CPR on somebody?”
“How did you know?” I said.
He said the paramedics had described me — “a tall doctor with glasses who was a nice guy.” It was funny that he knew that was me.
He told me, “The guy’s alive. He’s sick and needs to be put on dialysis, but he’s alive.”
Apparently, the guy had gone to the emergency department at North Naples, and the doctors in the emergency room (ER) worked on him for over an hour. They did continuous CPR and shocked him for close to 40 minutes. They finally got his pulse back, and after that, he was transferred to the main hospital ICU. They didn’t admit him at the ER, which was why I couldn’t find his name.
On Sunday, I was checking my patients’ charts for the ICU that coming week. And there he was. I saw his name and the documentation by the ED that CPR was provided by a critical care doctor in the field. He was still alive. That gave me so much joy.
So, the man I had helped became my patient. When I saw him on Monday, he was intubated and needed dialysis. I finally saw his face and thought, Oh, so that’s what you look like. I hadn’t realized he was only 39 years old.
When he was awake, I explained to him I was the doctor that provided CPR at the bar. He was very grateful, but of course, he didn’t remember anything.
Eventually, I met his daughter, and she just said, “Thank you for allowing me to have my dad.”
The funny part is that he broke his leg. Well, that’s not funny, but no one had any idea how it happened. That was his only complaint. He was asking me, “Doctor, how did you break my leg?”
“Hey, I have no idea how you broke your leg,” I replied. “I was trying to save your life.”
He was in the hospital for almost a month but made a full recovery. The amazing part: After all the evaluations, he has no neurological deficits. He’s back to a normal life now.
They never found a cause for the cardiac arrest. I mean, he had an ejection fraction of 10%. All my money was on something drug related, but that wasn’t the case. They’d done a cardiac cut, and there was no obstruction. They couldn’t find a reason.
We’ve become friends. He still works as a DJ at the bar. He changed his name to “DJ the Survivor” or something like that.
Sometimes, he’ll text me: “Doctor, what are you doing? You want to come down to the bar?”
I’m like, “No. I don’t.”
It’s been more than a year, but I remember every detail. When you go into medicine, you dream that one day you’ll be able to say, “I saved somebody.”
He texted me a year later and told me he’s celebrating two birthdays now. He said, “I’m turning 1 year old today!”
I think about the value of life. How we can take it for granted. We think, I’m young, nothing is going to happen to me. But this guy was 39. He went to work and died that night.
I was able to help bring him back. That makes me thankful for every day.
Jose Valle Giler, MD, is a pulmonary, critical care, and sleep medicine physician at NCH Healthcare System in Naples, Florida.
A version of this article appeared on Medscape.com .
EHR Copy and Paste Can Get Physicians Into Trouble
Physicians who misuse the “copy-and-paste” feature in patients’ electronic health records (EHRs) can face serious consequences, including lost hospital privileges, fines, and malpractice lawsuits.
In California, a locum tenens physician lost her hospital privileges after repeatedly violating the copy-and-paste policy developed at Santa Rosa Memorial Hospital, Santa Rosa, California.
“Her use of copy and paste impaired continuity of care,” said Alvin Gore, MD, who was involved in the case as the hospital’s director of utilization management.
Dr. Gore said the hospital warned the doctor, but she did not change her behavior. He did not identify the physician, citing confidentiality. The case occurred more than 5 years ago. Since then, several physicians have been called onto the carpet for violations of the policy, but no one else has lost privileges, Dr. Gore said.
“EHRs are imperfect, time consuming, and somewhat rigid,” said Robert A. Dowling, MD, a practice management consultant for large medical groups. “If physicians can’t easily figure out a complex system, they’re likely to use a workaround like copy and paste.”
Copy-and-paste abuse has also led to fines. A six-member cardiology group in Somerville, New Jersey, paid a $422,000 fine to the federal government to settle copy-and-paste charges, following an investigation by the Office of the Inspector General of the Department of Health and Human Services, according to the Report on Medicare Compliance.
This big settlement, announced in 2016, is a rare case in which physicians were charged with copy-and-paste fraud — intentionally using it to enhance reimbursement.
More commonly, Medicare contractors identify physicians who unintentionally received overpayments through sloppy copy-and-paste practices, according to a coding and documentation auditor who worked for 10 years at a Medicare contractor in Pennsylvania.
Such cases are frequent and are handled confidentially, said the auditor, who asked not to be identified. Practices must return the overpayment, and the physicians involved are “contacted and educated,” she said.
Copy and paste can also show up in malpractice lawsuits. In a 2012 survey, 53% of professional liability carriers said they had handled an EHR-related malpractice claim, and 71% of those claims included copy-and-paste use.
One such case, described by CRICO, a malpractice carrier based in Massachusetts, took place in 2012-2013. “A patient developed amiodarone toxicity because the patient›s history and medications were copied from a previous note that did not document that the patient was already on the medication,» CRICO stated.
“If you do face a malpractice claim, copying and pasting the same note repeatedly makes you look clinically inattentive, even if the copy/pasted material is unrelated to the adverse event,” CRICO officials noted in a report.
The Push to Use Copy and Paste
Copy and paste is a great time-saver. One study linked its use to lower burnout rates. However, it can easily introduce errors into the medical record. “This can be a huge problem,” Dr. Dowling said. “If, for example, you copy forward a previous note that said the patient had blood in their urine ‘6 days ago,’ it is immediately inaccurate.”
Practices can control use of copy and paste through coding clerks who read the medical records and then educate doctors when problems crop up.
The Pennsylvania auditor, who now works for a large group practice, said the group has very few copy-and-paste problems because of her role. “Not charting responsibly rarely happens because I work very closely with the doctors,” she said.
Dr. Dowling, however, reports that many physicians continue to overuse copy and paste. He points to a 2022 study which found that, on average, half the clinical note at one health system had been copied and pasted.
One solution might be to sanction physicians for overusing copy and paste, just as they’re sometimes penalized for not completing their notes on time with a reduction in income or possible termination.
Practices could periodically audit medical records for excessive copy-paste use. EHR systems like Epic’s can indicate how much of a doctor’s note has been copied. But Dr. Dowling doesn’t know of any practices that do this.
“There is little appetite to introduce a new enforcement activity for physicians,” he said. “Physicians would see it just as a way to make their lives more difficult than they already are.”
Monitoring in Hospitals and Health Systems
Some hospitals and health systems have gone as far as disabling copy-and-paste function in their EHR systems. However, enterprising physicians have found ways around these blocks.
Some institutions have also introduced formal policies, directing doctors on how they can copy and paste, including Banner Health in Arizona, Northwell Health in New York, UConn Health in Connecticut, University of Maryland Medical System, and University of Toledo in Ohio.
Definitions of what is not acceptable vary, but most of these policies oppose copying someone else’s notes and direct physicians to indicate the origin of pasted material.
Santa Rosa Memorial’s policy is quite specific. It still allows some copy and paste but stipulates that it cannot be used for the chief complaint, the review of systems, the physical examination, and the assessment and plan in the medical record, except when the information can’t be obtained directly from the patient. Also, physicians must summarize test results and provide references to other providers’ notes.
Dr. Gore said he and a physician educator who works with physicians on clinical documentation proposed the policy about a decade ago. When physicians on staff were asked to comment, some said they would be opposed to a complete ban, but they generally agreed that copy and paste was a serious problem that needed to be addressed, he said.
The hospital could have simply adopted guidelines, as opposed to rules with consequences, but “we wanted our policy to have teeth,” Dr. Gore said.
When violators are identified, Dr. Gore says he meets with them confidentially and educates them on proper use of copy and paste. Sometimes, the department head is brought in. Some physicians go on to violate the policy again and have to attend another meeting, he said, but aside from the one case, no one else has been disciplined.
It’s unclear how many physicians have faced consequences for misusing copy-paste features — such data aren’t tracked, and sanctions are likely to be handled confidentially, as a personnel matter.
Geisinger Health in Pennsylvania regularly monitors copy-and-paste usage and makes it part of physicians’ professional evaluations, according to a 2022 presentation by a Geisinger official.
Meanwhile, even when systems don’t have specific policies, they may still discipline physicians when copy and paste leads to errors. Scott MacDonald, MD, chief medical information officer at UC Davis Health in Sacramento, California, told this news organization that copy-and-paste abuse has come up a few times over the years in investigations of clinical errors.
Holding Physicians Accountable
Physicians can be held accountable for copy and paste by Medicare contractors and in malpractice lawsuits, but the most obvious way is at their place of work: A practice, hospital, or health system.
One physician has lost staff privileges, but more typically, coding clerks or colleagues talk to offending physicians and try to educate them on proper use of copy and paste.
Educational outreach, however, is often ineffective, said Robert Hirschtick, MD, a retired teaching physician at Northwestern University Feinberg School of Medicine, Chicago, Illinois. “The physician may be directed to take an online course,” he said. “When they take the course, the goal is to get it done with, rather than to learn something new.”
Dr. Hirschtick’s articles on copy and paste, including one titled, “Sloppy and Paste,” have put him at the front lines of the debate. “This is an ethical issue,” he said in an interview. He agrees that some forms of copy and paste are permissible, but in many cases, “it is intellectually dishonest and potentially even plagiarism,” he said.
Dr. Hirschtick argues that copy-and-paste policies need more teeth. “Tying violations to compensation would be quite effective,” he said. “Even if physicians were rarely penalized, just knowing that it could happen to you might be enough. But I haven’t heard of anyone doing this.”
A version of this article appeared on Medscape.com.
Physicians who misuse the “copy-and-paste” feature in patients’ electronic health records (EHRs) can face serious consequences, including lost hospital privileges, fines, and malpractice lawsuits.
In California, a locum tenens physician lost her hospital privileges after repeatedly violating the copy-and-paste policy developed at Santa Rosa Memorial Hospital, Santa Rosa, California.
“Her use of copy and paste impaired continuity of care,” said Alvin Gore, MD, who was involved in the case as the hospital’s director of utilization management.
Dr. Gore said the hospital warned the doctor, but she did not change her behavior. He did not identify the physician, citing confidentiality. The case occurred more than 5 years ago. Since then, several physicians have been called onto the carpet for violations of the policy, but no one else has lost privileges, Dr. Gore said.
“EHRs are imperfect, time consuming, and somewhat rigid,” said Robert A. Dowling, MD, a practice management consultant for large medical groups. “If physicians can’t easily figure out a complex system, they’re likely to use a workaround like copy and paste.”
Copy-and-paste abuse has also led to fines. A six-member cardiology group in Somerville, New Jersey, paid a $422,000 fine to the federal government to settle copy-and-paste charges, following an investigation by the Office of the Inspector General of the Department of Health and Human Services, according to the Report on Medicare Compliance.
This big settlement, announced in 2016, is a rare case in which physicians were charged with copy-and-paste fraud — intentionally using it to enhance reimbursement.
More commonly, Medicare contractors identify physicians who unintentionally received overpayments through sloppy copy-and-paste practices, according to a coding and documentation auditor who worked for 10 years at a Medicare contractor in Pennsylvania.
Such cases are frequent and are handled confidentially, said the auditor, who asked not to be identified. Practices must return the overpayment, and the physicians involved are “contacted and educated,” she said.
Copy and paste can also show up in malpractice lawsuits. In a 2012 survey, 53% of professional liability carriers said they had handled an EHR-related malpractice claim, and 71% of those claims included copy-and-paste use.
One such case, described by CRICO, a malpractice carrier based in Massachusetts, took place in 2012-2013. “A patient developed amiodarone toxicity because the patient›s history and medications were copied from a previous note that did not document that the patient was already on the medication,» CRICO stated.
“If you do face a malpractice claim, copying and pasting the same note repeatedly makes you look clinically inattentive, even if the copy/pasted material is unrelated to the adverse event,” CRICO officials noted in a report.
The Push to Use Copy and Paste
Copy and paste is a great time-saver. One study linked its use to lower burnout rates. However, it can easily introduce errors into the medical record. “This can be a huge problem,” Dr. Dowling said. “If, for example, you copy forward a previous note that said the patient had blood in their urine ‘6 days ago,’ it is immediately inaccurate.”
Practices can control use of copy and paste through coding clerks who read the medical records and then educate doctors when problems crop up.
The Pennsylvania auditor, who now works for a large group practice, said the group has very few copy-and-paste problems because of her role. “Not charting responsibly rarely happens because I work very closely with the doctors,” she said.
Dr. Dowling, however, reports that many physicians continue to overuse copy and paste. He points to a 2022 study which found that, on average, half the clinical note at one health system had been copied and pasted.
One solution might be to sanction physicians for overusing copy and paste, just as they’re sometimes penalized for not completing their notes on time with a reduction in income or possible termination.
Practices could periodically audit medical records for excessive copy-paste use. EHR systems like Epic’s can indicate how much of a doctor’s note has been copied. But Dr. Dowling doesn’t know of any practices that do this.
“There is little appetite to introduce a new enforcement activity for physicians,” he said. “Physicians would see it just as a way to make their lives more difficult than they already are.”
Monitoring in Hospitals and Health Systems
Some hospitals and health systems have gone as far as disabling copy-and-paste function in their EHR systems. However, enterprising physicians have found ways around these blocks.
Some institutions have also introduced formal policies, directing doctors on how they can copy and paste, including Banner Health in Arizona, Northwell Health in New York, UConn Health in Connecticut, University of Maryland Medical System, and University of Toledo in Ohio.
Definitions of what is not acceptable vary, but most of these policies oppose copying someone else’s notes and direct physicians to indicate the origin of pasted material.
Santa Rosa Memorial’s policy is quite specific. It still allows some copy and paste but stipulates that it cannot be used for the chief complaint, the review of systems, the physical examination, and the assessment and plan in the medical record, except when the information can’t be obtained directly from the patient. Also, physicians must summarize test results and provide references to other providers’ notes.
Dr. Gore said he and a physician educator who works with physicians on clinical documentation proposed the policy about a decade ago. When physicians on staff were asked to comment, some said they would be opposed to a complete ban, but they generally agreed that copy and paste was a serious problem that needed to be addressed, he said.
The hospital could have simply adopted guidelines, as opposed to rules with consequences, but “we wanted our policy to have teeth,” Dr. Gore said.
When violators are identified, Dr. Gore says he meets with them confidentially and educates them on proper use of copy and paste. Sometimes, the department head is brought in. Some physicians go on to violate the policy again and have to attend another meeting, he said, but aside from the one case, no one else has been disciplined.
It’s unclear how many physicians have faced consequences for misusing copy-paste features — such data aren’t tracked, and sanctions are likely to be handled confidentially, as a personnel matter.
Geisinger Health in Pennsylvania regularly monitors copy-and-paste usage and makes it part of physicians’ professional evaluations, according to a 2022 presentation by a Geisinger official.
Meanwhile, even when systems don’t have specific policies, they may still discipline physicians when copy and paste leads to errors. Scott MacDonald, MD, chief medical information officer at UC Davis Health in Sacramento, California, told this news organization that copy-and-paste abuse has come up a few times over the years in investigations of clinical errors.
Holding Physicians Accountable
Physicians can be held accountable for copy and paste by Medicare contractors and in malpractice lawsuits, but the most obvious way is at their place of work: A practice, hospital, or health system.
One physician has lost staff privileges, but more typically, coding clerks or colleagues talk to offending physicians and try to educate them on proper use of copy and paste.
Educational outreach, however, is often ineffective, said Robert Hirschtick, MD, a retired teaching physician at Northwestern University Feinberg School of Medicine, Chicago, Illinois. “The physician may be directed to take an online course,” he said. “When they take the course, the goal is to get it done with, rather than to learn something new.”
Dr. Hirschtick’s articles on copy and paste, including one titled, “Sloppy and Paste,” have put him at the front lines of the debate. “This is an ethical issue,” he said in an interview. He agrees that some forms of copy and paste are permissible, but in many cases, “it is intellectually dishonest and potentially even plagiarism,” he said.
Dr. Hirschtick argues that copy-and-paste policies need more teeth. “Tying violations to compensation would be quite effective,” he said. “Even if physicians were rarely penalized, just knowing that it could happen to you might be enough. But I haven’t heard of anyone doing this.”
A version of this article appeared on Medscape.com.
Physicians who misuse the “copy-and-paste” feature in patients’ electronic health records (EHRs) can face serious consequences, including lost hospital privileges, fines, and malpractice lawsuits.
In California, a locum tenens physician lost her hospital privileges after repeatedly violating the copy-and-paste policy developed at Santa Rosa Memorial Hospital, Santa Rosa, California.
“Her use of copy and paste impaired continuity of care,” said Alvin Gore, MD, who was involved in the case as the hospital’s director of utilization management.
Dr. Gore said the hospital warned the doctor, but she did not change her behavior. He did not identify the physician, citing confidentiality. The case occurred more than 5 years ago. Since then, several physicians have been called onto the carpet for violations of the policy, but no one else has lost privileges, Dr. Gore said.
“EHRs are imperfect, time consuming, and somewhat rigid,” said Robert A. Dowling, MD, a practice management consultant for large medical groups. “If physicians can’t easily figure out a complex system, they’re likely to use a workaround like copy and paste.”
Copy-and-paste abuse has also led to fines. A six-member cardiology group in Somerville, New Jersey, paid a $422,000 fine to the federal government to settle copy-and-paste charges, following an investigation by the Office of the Inspector General of the Department of Health and Human Services, according to the Report on Medicare Compliance.
This big settlement, announced in 2016, is a rare case in which physicians were charged with copy-and-paste fraud — intentionally using it to enhance reimbursement.
More commonly, Medicare contractors identify physicians who unintentionally received overpayments through sloppy copy-and-paste practices, according to a coding and documentation auditor who worked for 10 years at a Medicare contractor in Pennsylvania.
Such cases are frequent and are handled confidentially, said the auditor, who asked not to be identified. Practices must return the overpayment, and the physicians involved are “contacted and educated,” she said.
Copy and paste can also show up in malpractice lawsuits. In a 2012 survey, 53% of professional liability carriers said they had handled an EHR-related malpractice claim, and 71% of those claims included copy-and-paste use.
One such case, described by CRICO, a malpractice carrier based in Massachusetts, took place in 2012-2013. “A patient developed amiodarone toxicity because the patient›s history and medications were copied from a previous note that did not document that the patient was already on the medication,» CRICO stated.
“If you do face a malpractice claim, copying and pasting the same note repeatedly makes you look clinically inattentive, even if the copy/pasted material is unrelated to the adverse event,” CRICO officials noted in a report.
The Push to Use Copy and Paste
Copy and paste is a great time-saver. One study linked its use to lower burnout rates. However, it can easily introduce errors into the medical record. “This can be a huge problem,” Dr. Dowling said. “If, for example, you copy forward a previous note that said the patient had blood in their urine ‘6 days ago,’ it is immediately inaccurate.”
Practices can control use of copy and paste through coding clerks who read the medical records and then educate doctors when problems crop up.
The Pennsylvania auditor, who now works for a large group practice, said the group has very few copy-and-paste problems because of her role. “Not charting responsibly rarely happens because I work very closely with the doctors,” she said.
Dr. Dowling, however, reports that many physicians continue to overuse copy and paste. He points to a 2022 study which found that, on average, half the clinical note at one health system had been copied and pasted.
One solution might be to sanction physicians for overusing copy and paste, just as they’re sometimes penalized for not completing their notes on time with a reduction in income or possible termination.
Practices could periodically audit medical records for excessive copy-paste use. EHR systems like Epic’s can indicate how much of a doctor’s note has been copied. But Dr. Dowling doesn’t know of any practices that do this.
“There is little appetite to introduce a new enforcement activity for physicians,” he said. “Physicians would see it just as a way to make their lives more difficult than they already are.”
Monitoring in Hospitals and Health Systems
Some hospitals and health systems have gone as far as disabling copy-and-paste function in their EHR systems. However, enterprising physicians have found ways around these blocks.
Some institutions have also introduced formal policies, directing doctors on how they can copy and paste, including Banner Health in Arizona, Northwell Health in New York, UConn Health in Connecticut, University of Maryland Medical System, and University of Toledo in Ohio.
Definitions of what is not acceptable vary, but most of these policies oppose copying someone else’s notes and direct physicians to indicate the origin of pasted material.
Santa Rosa Memorial’s policy is quite specific. It still allows some copy and paste but stipulates that it cannot be used for the chief complaint, the review of systems, the physical examination, and the assessment and plan in the medical record, except when the information can’t be obtained directly from the patient. Also, physicians must summarize test results and provide references to other providers’ notes.
Dr. Gore said he and a physician educator who works with physicians on clinical documentation proposed the policy about a decade ago. When physicians on staff were asked to comment, some said they would be opposed to a complete ban, but they generally agreed that copy and paste was a serious problem that needed to be addressed, he said.
The hospital could have simply adopted guidelines, as opposed to rules with consequences, but “we wanted our policy to have teeth,” Dr. Gore said.
When violators are identified, Dr. Gore says he meets with them confidentially and educates them on proper use of copy and paste. Sometimes, the department head is brought in. Some physicians go on to violate the policy again and have to attend another meeting, he said, but aside from the one case, no one else has been disciplined.
It’s unclear how many physicians have faced consequences for misusing copy-paste features — such data aren’t tracked, and sanctions are likely to be handled confidentially, as a personnel matter.
Geisinger Health in Pennsylvania regularly monitors copy-and-paste usage and makes it part of physicians’ professional evaluations, according to a 2022 presentation by a Geisinger official.
Meanwhile, even when systems don’t have specific policies, they may still discipline physicians when copy and paste leads to errors. Scott MacDonald, MD, chief medical information officer at UC Davis Health in Sacramento, California, told this news organization that copy-and-paste abuse has come up a few times over the years in investigations of clinical errors.
Holding Physicians Accountable
Physicians can be held accountable for copy and paste by Medicare contractors and in malpractice lawsuits, but the most obvious way is at their place of work: A practice, hospital, or health system.
One physician has lost staff privileges, but more typically, coding clerks or colleagues talk to offending physicians and try to educate them on proper use of copy and paste.
Educational outreach, however, is often ineffective, said Robert Hirschtick, MD, a retired teaching physician at Northwestern University Feinberg School of Medicine, Chicago, Illinois. “The physician may be directed to take an online course,” he said. “When they take the course, the goal is to get it done with, rather than to learn something new.”
Dr. Hirschtick’s articles on copy and paste, including one titled, “Sloppy and Paste,” have put him at the front lines of the debate. “This is an ethical issue,” he said in an interview. He agrees that some forms of copy and paste are permissible, but in many cases, “it is intellectually dishonest and potentially even plagiarism,” he said.
Dr. Hirschtick argues that copy-and-paste policies need more teeth. “Tying violations to compensation would be quite effective,” he said. “Even if physicians were rarely penalized, just knowing that it could happen to you might be enough. But I haven’t heard of anyone doing this.”
A version of this article appeared on Medscape.com.
European Scientists Assess Avian Flu Pandemic Risk
As avian influenza continues to spread among wild bird populations in the European Union (EU), scientists have described a wide range of factors that could drive the virus to spread efficiently among humans, thereby increasing its pandemic potential.
Although transmission of avian influenza A(H5N1) from infected birds to humans is rare, “new strains carrying potential mutations for mammalian adaptation” could occur, according to a report issued on April 3 by the European Centre for Disease Prevention and Control and the European Food Safety Authority. The analysis identified a threat of strains currently circulating outside Europe that could enter the EU and the wider European Economic Area (EEA).
“If avian A(H5N1) influenza viruses acquire the ability to spread efficiently among humans, large-scale transmission could occur due to the lack of immune defenses against H5 viruses in humans,” the report warned.
Evolution of Avian Influenza Remains Hard to Predict
However, despite many occurrences of human exposure to avian influenza since 2020, “no symptomatic or productive infection in a human has been identified in the EU/EEA,” the scientists stated. Furthermore, after almost three decades of human exposure to the A(H5N1) virus of the Gs/GD lineage, the virus has not yet acquired the mutations required for airborne transmissibility between humans. However, it remains “difficult to predict the evolutionary direction the virus will take in the future,” the scientists assessed.
“Clearly, humans are being exposed in the current USA cattle outbreak,” Professor James Wood, infectious disease epidemiologist at the University of Cambridge, United Kingdom, told this news organization. “But, arguably, what is more significant is how few cases there have been with this virus lineage and its close relatives, despite massive global exposures over the last 3 years. All diagnosed human cases seem to have been singletons, with no evidence of human-to-human transmission.”
Ian Jones, professor of virology at the University of Reading, United Kingdom, sees no evidence of an imminent spillover of avian influenza from birds. But he told this news organization: “The trouble is, the clock resets every minute. Every time the virus has come out of a bird and gone somewhere, the clock is reset. So you can never say that just because it hasn’t happened since whenever, it’s never going to happen.”
Preventive Measures Recommended
The European report recommended a range of cautionary measures that included enhanced surveillance, access to rapid diagnostics, and sharing of genetic sequence data. It urged EU authorities to work together, adopting a One Health perspective, to limit the exposure of mammals, including humans, to avian influenza viruses.
Sarah Pitt, a microbiologist at the University of Brighton, United Kingdom, said the emphasis on authorities taking a One Health approach was sound. “You’re looking at humans, animals, plants, and the environment and how they’re all closely interacted,” she told this news organization. “Putting all those things together is actually going to be good for human health. So they’ve mentioned One Health a lot and I’m sure that’s on purpose because it’s the latest buzzword, and presumably it’s a way of getting governments to take it seriously.”
Overall, Dr. Pitt believes the document is designed to move zoonotic infectious diseases a bit higher up the agenda. “They should have been higher up the agenda before COVID,” she said.
The report also called for consideration of preventative measures, such as vaccination of poultry flocks.
Overall, Dr. Jones assesses the European report as “a reworking of what’s been pretty well covered over the years.” Despite extensive work by scientists in the field, he said: “I’m not sure we’re any better at predicting an emerging virus than we’ve ever been. I would point out that we didn’t spot SARS-CoV-2 coming, even though we had SARS-CoV-1 a few years earlier. Nobody spotted the 2009 pandemic from influenza, even though there was a lot of surveillance around at the time.”
A version of this article appeared on Medscape.com.
As avian influenza continues to spread among wild bird populations in the European Union (EU), scientists have described a wide range of factors that could drive the virus to spread efficiently among humans, thereby increasing its pandemic potential.
Although transmission of avian influenza A(H5N1) from infected birds to humans is rare, “new strains carrying potential mutations for mammalian adaptation” could occur, according to a report issued on April 3 by the European Centre for Disease Prevention and Control and the European Food Safety Authority. The analysis identified a threat of strains currently circulating outside Europe that could enter the EU and the wider European Economic Area (EEA).
“If avian A(H5N1) influenza viruses acquire the ability to spread efficiently among humans, large-scale transmission could occur due to the lack of immune defenses against H5 viruses in humans,” the report warned.
Evolution of Avian Influenza Remains Hard to Predict
However, despite many occurrences of human exposure to avian influenza since 2020, “no symptomatic or productive infection in a human has been identified in the EU/EEA,” the scientists stated. Furthermore, after almost three decades of human exposure to the A(H5N1) virus of the Gs/GD lineage, the virus has not yet acquired the mutations required for airborne transmissibility between humans. However, it remains “difficult to predict the evolutionary direction the virus will take in the future,” the scientists assessed.
“Clearly, humans are being exposed in the current USA cattle outbreak,” Professor James Wood, infectious disease epidemiologist at the University of Cambridge, United Kingdom, told this news organization. “But, arguably, what is more significant is how few cases there have been with this virus lineage and its close relatives, despite massive global exposures over the last 3 years. All diagnosed human cases seem to have been singletons, with no evidence of human-to-human transmission.”
Ian Jones, professor of virology at the University of Reading, United Kingdom, sees no evidence of an imminent spillover of avian influenza from birds. But he told this news organization: “The trouble is, the clock resets every minute. Every time the virus has come out of a bird and gone somewhere, the clock is reset. So you can never say that just because it hasn’t happened since whenever, it’s never going to happen.”
Preventive Measures Recommended
The European report recommended a range of cautionary measures that included enhanced surveillance, access to rapid diagnostics, and sharing of genetic sequence data. It urged EU authorities to work together, adopting a One Health perspective, to limit the exposure of mammals, including humans, to avian influenza viruses.
Sarah Pitt, a microbiologist at the University of Brighton, United Kingdom, said the emphasis on authorities taking a One Health approach was sound. “You’re looking at humans, animals, plants, and the environment and how they’re all closely interacted,” she told this news organization. “Putting all those things together is actually going to be good for human health. So they’ve mentioned One Health a lot and I’m sure that’s on purpose because it’s the latest buzzword, and presumably it’s a way of getting governments to take it seriously.”
Overall, Dr. Pitt believes the document is designed to move zoonotic infectious diseases a bit higher up the agenda. “They should have been higher up the agenda before COVID,” she said.
The report also called for consideration of preventative measures, such as vaccination of poultry flocks.
Overall, Dr. Jones assesses the European report as “a reworking of what’s been pretty well covered over the years.” Despite extensive work by scientists in the field, he said: “I’m not sure we’re any better at predicting an emerging virus than we’ve ever been. I would point out that we didn’t spot SARS-CoV-2 coming, even though we had SARS-CoV-1 a few years earlier. Nobody spotted the 2009 pandemic from influenza, even though there was a lot of surveillance around at the time.”
A version of this article appeared on Medscape.com.
As avian influenza continues to spread among wild bird populations in the European Union (EU), scientists have described a wide range of factors that could drive the virus to spread efficiently among humans, thereby increasing its pandemic potential.
Although transmission of avian influenza A(H5N1) from infected birds to humans is rare, “new strains carrying potential mutations for mammalian adaptation” could occur, according to a report issued on April 3 by the European Centre for Disease Prevention and Control and the European Food Safety Authority. The analysis identified a threat of strains currently circulating outside Europe that could enter the EU and the wider European Economic Area (EEA).
“If avian A(H5N1) influenza viruses acquire the ability to spread efficiently among humans, large-scale transmission could occur due to the lack of immune defenses against H5 viruses in humans,” the report warned.
Evolution of Avian Influenza Remains Hard to Predict
However, despite many occurrences of human exposure to avian influenza since 2020, “no symptomatic or productive infection in a human has been identified in the EU/EEA,” the scientists stated. Furthermore, after almost three decades of human exposure to the A(H5N1) virus of the Gs/GD lineage, the virus has not yet acquired the mutations required for airborne transmissibility between humans. However, it remains “difficult to predict the evolutionary direction the virus will take in the future,” the scientists assessed.
“Clearly, humans are being exposed in the current USA cattle outbreak,” Professor James Wood, infectious disease epidemiologist at the University of Cambridge, United Kingdom, told this news organization. “But, arguably, what is more significant is how few cases there have been with this virus lineage and its close relatives, despite massive global exposures over the last 3 years. All diagnosed human cases seem to have been singletons, with no evidence of human-to-human transmission.”
Ian Jones, professor of virology at the University of Reading, United Kingdom, sees no evidence of an imminent spillover of avian influenza from birds. But he told this news organization: “The trouble is, the clock resets every minute. Every time the virus has come out of a bird and gone somewhere, the clock is reset. So you can never say that just because it hasn’t happened since whenever, it’s never going to happen.”
Preventive Measures Recommended
The European report recommended a range of cautionary measures that included enhanced surveillance, access to rapid diagnostics, and sharing of genetic sequence data. It urged EU authorities to work together, adopting a One Health perspective, to limit the exposure of mammals, including humans, to avian influenza viruses.
Sarah Pitt, a microbiologist at the University of Brighton, United Kingdom, said the emphasis on authorities taking a One Health approach was sound. “You’re looking at humans, animals, plants, and the environment and how they’re all closely interacted,” she told this news organization. “Putting all those things together is actually going to be good for human health. So they’ve mentioned One Health a lot and I’m sure that’s on purpose because it’s the latest buzzword, and presumably it’s a way of getting governments to take it seriously.”
Overall, Dr. Pitt believes the document is designed to move zoonotic infectious diseases a bit higher up the agenda. “They should have been higher up the agenda before COVID,” she said.
The report also called for consideration of preventative measures, such as vaccination of poultry flocks.
Overall, Dr. Jones assesses the European report as “a reworking of what’s been pretty well covered over the years.” Despite extensive work by scientists in the field, he said: “I’m not sure we’re any better at predicting an emerging virus than we’ve ever been. I would point out that we didn’t spot SARS-CoV-2 coming, even though we had SARS-CoV-1 a few years earlier. Nobody spotted the 2009 pandemic from influenza, even though there was a lot of surveillance around at the time.”
A version of this article appeared on Medscape.com.
Hepatitis E Vaccine Shows Long-Term Efficacy
The hepatitis E virus (HEV) is among the leading global causes of acute viral hepatitis. Molecular studies of HEV strains have identified four main genotypes. Genotypes 1 and 2 are limited to humans and are transmitted through contaminated water in resource-limited countries, mainly in Asia. Genotypes 3 and 4 are zoonotic, causing sporadic indigenous hepatitis E in nearly all countries.
Each year, approximately 20 million HEV infections occur worldwide, resulting in around 3.3 million symptomatic infections and 70,000 deaths. Despite this toll, HEV infection remains underestimated, and Western countries are likely not immune to the virus. To date, two recombinant vaccines against hepatitis E, based on genotype 1, have been developed and approved in China, but further studies are needed to determine the duration of vaccination protection.
Ten-Year Results
This study is an extension of a randomized, double-blind, placebo-controlled phase 3 clinical trial of the Hecolin hepatitis E vaccine that was conducted in Dongtai County, Jiangsu, China. In the initial trial, healthy adults aged 16-65 years were recruited, stratified by age and sex, and randomly assigned in a 1:1 ratio to receive three doses of intramuscular hepatitis E vaccine or placebo at months 0, 1, and 6.
A hepatitis E surveillance system, including 205 clinical sentinels covering the entire study region, was established before the study began and maintained for 10 years after vaccination to identify individuals with suspected hepatitis. In addition, an external control cohort was formed to assess vaccine efficacy. The primary endpoint was the vaccine’s efficacy in preventing confirmed hepatitis E occurring at least 30 days after the administration of the third vaccine dose.
Follow-up occurred every 3 months. Participants with hepatitis symptoms for 3 days or more underwent alanine aminotransferase (ALT) concentration measurement. Patients with ALT concentrations ≥ 2.5 times the upper limit of normal were considered to have acute hepatitis. A diagnosis of HEV-confirmed infection was made for patients with acute hepatitis presenting with at least two of the following markers: Presence of HEV RNA, presence of positive anti-HEV immunoglobulin (Ig) M antibodies, and at least fourfold increase in anti-HEV IgG concentrations.
For the efficacy analysis, a Poisson regression model was used to estimate the relative risk and its 95% CI of incidence between groups. Incidence was reported as the number of patients with hepatitis E per 10,000 person-years.
Immunogenicity persistence was assessed by measuring anti-HEV IgG in participants. Serum samples were collected at months 0, 7, 13, 19, 31, 43, 55, 79, and 103 for Qingdao district participants and at months 0, 7, 19, 31, 43, 67, and 91 for Anfeng district participants.
Efficacy and Duration
The follow-up period extended from 2007 to 2017. In total, 97,356 participants completed the three-dose regimen and were included in the per-protocol population (48,693 in the vaccine group and 48,663 in the placebo group), and 178,236 residents from the study region participated in the external control cohort. During the study period, 90 cases of hepatitis E were identified, with 13 in the vaccine group (0.2 per 10,000 person-years) and 77 in the placebo group (1.4 per 10,000 person-years). This indicated a vaccine efficacy of 86.6% in the per-protocol analysis.
In the subgroups evaluated for immunogenicity persistence, among those who were initially seronegative and received three doses of hepatitis E vaccine, 254 out of 291 vaccinated participants (87.3%) in Qingdao after 8.5 years and 1270 (73.0%) out of 1740 vaccinated participants in Anfeng after 7.5 years maintained detectable antibody concentrations.
The identification of infections despite vaccination is notable, especially with eight cases occurring beyond the fourth year following the last dose. This information is crucial for understanding potential immunity decline over time and highlights the importance of exploring various vaccination strategies to optimize protection.
An ongoing phase 4 clinical trial in Bangladesh, exploring different administration schedules and target populations, could help optimize vaccination strategies. The remarkable efficacy (100%) observed over a 30-month period for the two-dose schedule (doses are administered 1 month apart) is promising.
The observation of higher IgG antibody avidity in participants with infections despite vaccination underscores the importance of robust antibody responses to mitigate disease severity and duration. Several study limitations, such as lack of data on deaths and emigrations, a single-center study design, predominance of genotype 4 infections, and the risk for bias in the external control cohort, should be acknowledged.
In conclusion, this study provides compelling evidence of sustained protection of the hepatitis E vaccine over a decade. The observed persistence of induced antibodies for at least 8.5 years supports the long-term efficacy of the vaccine. Diverse global trials, further investigation into the impact of natural infections on vaccine-induced antibodies, and confirmation of inter-genotypic protection are needed.
This story was translated from JIM, which is part of the Medscape professional network, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
The hepatitis E virus (HEV) is among the leading global causes of acute viral hepatitis. Molecular studies of HEV strains have identified four main genotypes. Genotypes 1 and 2 are limited to humans and are transmitted through contaminated water in resource-limited countries, mainly in Asia. Genotypes 3 and 4 are zoonotic, causing sporadic indigenous hepatitis E in nearly all countries.
Each year, approximately 20 million HEV infections occur worldwide, resulting in around 3.3 million symptomatic infections and 70,000 deaths. Despite this toll, HEV infection remains underestimated, and Western countries are likely not immune to the virus. To date, two recombinant vaccines against hepatitis E, based on genotype 1, have been developed and approved in China, but further studies are needed to determine the duration of vaccination protection.
Ten-Year Results
This study is an extension of a randomized, double-blind, placebo-controlled phase 3 clinical trial of the Hecolin hepatitis E vaccine that was conducted in Dongtai County, Jiangsu, China. In the initial trial, healthy adults aged 16-65 years were recruited, stratified by age and sex, and randomly assigned in a 1:1 ratio to receive three doses of intramuscular hepatitis E vaccine or placebo at months 0, 1, and 6.
A hepatitis E surveillance system, including 205 clinical sentinels covering the entire study region, was established before the study began and maintained for 10 years after vaccination to identify individuals with suspected hepatitis. In addition, an external control cohort was formed to assess vaccine efficacy. The primary endpoint was the vaccine’s efficacy in preventing confirmed hepatitis E occurring at least 30 days after the administration of the third vaccine dose.
Follow-up occurred every 3 months. Participants with hepatitis symptoms for 3 days or more underwent alanine aminotransferase (ALT) concentration measurement. Patients with ALT concentrations ≥ 2.5 times the upper limit of normal were considered to have acute hepatitis. A diagnosis of HEV-confirmed infection was made for patients with acute hepatitis presenting with at least two of the following markers: Presence of HEV RNA, presence of positive anti-HEV immunoglobulin (Ig) M antibodies, and at least fourfold increase in anti-HEV IgG concentrations.
For the efficacy analysis, a Poisson regression model was used to estimate the relative risk and its 95% CI of incidence between groups. Incidence was reported as the number of patients with hepatitis E per 10,000 person-years.
Immunogenicity persistence was assessed by measuring anti-HEV IgG in participants. Serum samples were collected at months 0, 7, 13, 19, 31, 43, 55, 79, and 103 for Qingdao district participants and at months 0, 7, 19, 31, 43, 67, and 91 for Anfeng district participants.
Efficacy and Duration
The follow-up period extended from 2007 to 2017. In total, 97,356 participants completed the three-dose regimen and were included in the per-protocol population (48,693 in the vaccine group and 48,663 in the placebo group), and 178,236 residents from the study region participated in the external control cohort. During the study period, 90 cases of hepatitis E were identified, with 13 in the vaccine group (0.2 per 10,000 person-years) and 77 in the placebo group (1.4 per 10,000 person-years). This indicated a vaccine efficacy of 86.6% in the per-protocol analysis.
In the subgroups evaluated for immunogenicity persistence, among those who were initially seronegative and received three doses of hepatitis E vaccine, 254 out of 291 vaccinated participants (87.3%) in Qingdao after 8.5 years and 1270 (73.0%) out of 1740 vaccinated participants in Anfeng after 7.5 years maintained detectable antibody concentrations.
The identification of infections despite vaccination is notable, especially with eight cases occurring beyond the fourth year following the last dose. This information is crucial for understanding potential immunity decline over time and highlights the importance of exploring various vaccination strategies to optimize protection.
An ongoing phase 4 clinical trial in Bangladesh, exploring different administration schedules and target populations, could help optimize vaccination strategies. The remarkable efficacy (100%) observed over a 30-month period for the two-dose schedule (doses are administered 1 month apart) is promising.
The observation of higher IgG antibody avidity in participants with infections despite vaccination underscores the importance of robust antibody responses to mitigate disease severity and duration. Several study limitations, such as lack of data on deaths and emigrations, a single-center study design, predominance of genotype 4 infections, and the risk for bias in the external control cohort, should be acknowledged.
In conclusion, this study provides compelling evidence of sustained protection of the hepatitis E vaccine over a decade. The observed persistence of induced antibodies for at least 8.5 years supports the long-term efficacy of the vaccine. Diverse global trials, further investigation into the impact of natural infections on vaccine-induced antibodies, and confirmation of inter-genotypic protection are needed.
This story was translated from JIM, which is part of the Medscape professional network, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
The hepatitis E virus (HEV) is among the leading global causes of acute viral hepatitis. Molecular studies of HEV strains have identified four main genotypes. Genotypes 1 and 2 are limited to humans and are transmitted through contaminated water in resource-limited countries, mainly in Asia. Genotypes 3 and 4 are zoonotic, causing sporadic indigenous hepatitis E in nearly all countries.
Each year, approximately 20 million HEV infections occur worldwide, resulting in around 3.3 million symptomatic infections and 70,000 deaths. Despite this toll, HEV infection remains underestimated, and Western countries are likely not immune to the virus. To date, two recombinant vaccines against hepatitis E, based on genotype 1, have been developed and approved in China, but further studies are needed to determine the duration of vaccination protection.
Ten-Year Results
This study is an extension of a randomized, double-blind, placebo-controlled phase 3 clinical trial of the Hecolin hepatitis E vaccine that was conducted in Dongtai County, Jiangsu, China. In the initial trial, healthy adults aged 16-65 years were recruited, stratified by age and sex, and randomly assigned in a 1:1 ratio to receive three doses of intramuscular hepatitis E vaccine or placebo at months 0, 1, and 6.
A hepatitis E surveillance system, including 205 clinical sentinels covering the entire study region, was established before the study began and maintained for 10 years after vaccination to identify individuals with suspected hepatitis. In addition, an external control cohort was formed to assess vaccine efficacy. The primary endpoint was the vaccine’s efficacy in preventing confirmed hepatitis E occurring at least 30 days after the administration of the third vaccine dose.
Follow-up occurred every 3 months. Participants with hepatitis symptoms for 3 days or more underwent alanine aminotransferase (ALT) concentration measurement. Patients with ALT concentrations ≥ 2.5 times the upper limit of normal were considered to have acute hepatitis. A diagnosis of HEV-confirmed infection was made for patients with acute hepatitis presenting with at least two of the following markers: Presence of HEV RNA, presence of positive anti-HEV immunoglobulin (Ig) M antibodies, and at least fourfold increase in anti-HEV IgG concentrations.
For the efficacy analysis, a Poisson regression model was used to estimate the relative risk and its 95% CI of incidence between groups. Incidence was reported as the number of patients with hepatitis E per 10,000 person-years.
Immunogenicity persistence was assessed by measuring anti-HEV IgG in participants. Serum samples were collected at months 0, 7, 13, 19, 31, 43, 55, 79, and 103 for Qingdao district participants and at months 0, 7, 19, 31, 43, 67, and 91 for Anfeng district participants.
Efficacy and Duration
The follow-up period extended from 2007 to 2017. In total, 97,356 participants completed the three-dose regimen and were included in the per-protocol population (48,693 in the vaccine group and 48,663 in the placebo group), and 178,236 residents from the study region participated in the external control cohort. During the study period, 90 cases of hepatitis E were identified, with 13 in the vaccine group (0.2 per 10,000 person-years) and 77 in the placebo group (1.4 per 10,000 person-years). This indicated a vaccine efficacy of 86.6% in the per-protocol analysis.
In the subgroups evaluated for immunogenicity persistence, among those who were initially seronegative and received three doses of hepatitis E vaccine, 254 out of 291 vaccinated participants (87.3%) in Qingdao after 8.5 years and 1270 (73.0%) out of 1740 vaccinated participants in Anfeng after 7.5 years maintained detectable antibody concentrations.
The identification of infections despite vaccination is notable, especially with eight cases occurring beyond the fourth year following the last dose. This information is crucial for understanding potential immunity decline over time and highlights the importance of exploring various vaccination strategies to optimize protection.
An ongoing phase 4 clinical trial in Bangladesh, exploring different administration schedules and target populations, could help optimize vaccination strategies. The remarkable efficacy (100%) observed over a 30-month period for the two-dose schedule (doses are administered 1 month apart) is promising.
The observation of higher IgG antibody avidity in participants with infections despite vaccination underscores the importance of robust antibody responses to mitigate disease severity and duration. Several study limitations, such as lack of data on deaths and emigrations, a single-center study design, predominance of genotype 4 infections, and the risk for bias in the external control cohort, should be acknowledged.
In conclusion, this study provides compelling evidence of sustained protection of the hepatitis E vaccine over a decade. The observed persistence of induced antibodies for at least 8.5 years supports the long-term efficacy of the vaccine. Diverse global trials, further investigation into the impact of natural infections on vaccine-induced antibodies, and confirmation of inter-genotypic protection are needed.
This story was translated from JIM, which is part of the Medscape professional network, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
Consider Skin Cancer, Infection Risks in Solid Organ Transplant Recipients
SAN DIEGO —
because of their suppressed immune systems.“There are over 450,000 people with a solid organ transplant living in the United States. If you do the math, that works out to about 40 organ transplant recipients for every dermatologist, so there’s a lot of them out there for us to take care of,” Sean Christensen, MD, PhD, associate professor of dermatology, Yale University, New Haven, Connecticut, said at the annual meeting of the American Academy of Dermatology (AAD). “If we expand that umbrella to include all types of immunosuppression, that’s over 4 million adults in the US.”
Dr. Christensen encouraged dermatologists to be aware of the varying risks for immunosuppressive drugs and best screening practices for these patients, and to take advantage of a validated skin cancer risk assessment tool for transplant patients.
During his presentation, he highlighted five classes of immunosuppressive drugs and their associated skin cancer risks:
- Calcineurin inhibitors (tacrolimus or cyclosporine), which cause severe immune suppression and pose a severe skin cancer risk. They may also cause gingival hyperplasia and sebaceous hyperplasia.
- Antimetabolites (mycophenolate mofetil or azathioprine), which cause moderate to severe immune suppression and pose a severe skin cancer risk.
- Mammalian target of rapamycin inhibitors (sirolimus or everolimus), which cause severe immune suppression and pose a moderate skin cancer risk. They also impair wound healing.
- Corticosteroids (prednisone), which cause mild to severe immune suppression and pose a minimal skin cancer risk.
- A decoy receptor protein (belatacept), which causes severe immune suppression and poses a mild skin cancer risk.
“Most of our solid-organ transplant recipients will be on both a calcineurin inhibitor and an antimetabolite,” Dr. Christensen said. “In addition to the skin cancer risk associated with immunosuppression, there is an additive risk” that is a direct effect of these medications on the skin. “That means our transplant recipients have a severely and disproportionate increase in skin cancer,” he noted.
Up to half of solid-organ transplant recipients will develop skin cancer, Dr. Christensen said. These patients have a sixfold to 10-fold increased risk for basal cell carcinoma (BCC), a 35- to 65-fold increased risk for squamous cell carcinoma (SCC), a twofold to sevenfold increased risk for melanoma, and a 16- to 100-fold increased risk for Merkel cell carcinoma.
Transplant recipients with SCC, he said, have a twofold to threefold higher risk for metastasis (4%-8% nodal metastasis) and twofold to fivefold higher risk for death (2%-7% mortality) from SCC.
As for other kinds of immunosuppression, HIV positivity, treatment with 6-mercaptopurine or azathioprine (for inflammatory bowel disease and rheumatoid arthritis), and antitumor necrosis factor agents (for psoriasis, inflammatory bowel disease, and rheumatoid arthritis) have been linked in studies to a higher risk for nonmelanoma skin cancer.
Dr. Christensen also highlighted graft-versus-host disease (GVHD). “It does look like there is a disproportionate and increased risk of SCC of the oropharynx and of the skin in patients who have chronic GVHD. This is probably due to a combination of both the immunosuppressive medications that are required but also from chronic and ongoing inflammation in the skin.”
Chronic GVHD has been linked to a 5.3-fold increase in the risk for SCC and a twofold increase in the risk for BCC, he added.
Moreover, new medications for treating GVHD have been linked to an increased risk for SCC, including a 3.2-fold increased risk for SCC associated with ruxolitinib, a Janus kinase (JAK) 1 and JAK2 inhibitor, in a study of patients with polycythemia vera and myelofibrosis; and a case report of SCC in a patient treated with belumosudil, a rho-associated coiled-coil-containing protein kinase-2 kinase inhibitor, for chronic GVHD. Risk for SCC appears to increase based on duration of use with voriconazole, an antifungal, which, he said, is a potent photosynthesizer.
Dr. Christensen also noted the higher risk for infections in immunocompromised patients and added that these patients can develop inflammatory disease despite immunosuppression:
Staphylococcus, Streptococcus, and Dermatophytes are the most common skin pathogens in these patients. There’s a significantly increased risk for reactivation of herpes simplex, varicella-zoster viruses, and cytomegalovirus. Opportunistic and disseminated fungal infections, such as mycobacteria, Candida, histoplasma, cryptococcus, aspergillus, and mucormycosis, can also appear.
More than 80% of transplant recipients develop molluscum and verruca vulgaris/human papillomavirus infection. They may also develop noninfectious inflammatory dermatoses.
Risk Calculator
What can dermatologists do to help transplant patients? Dr. Christensen highlighted the Skin and UV Neoplasia Transplant Risk Assessment Calculator, which predicts skin cancer risk based on points given for race, gender, skin cancer history, age at transplant, and site of transplant.
The tool, validated in a 2023 study of transplant recipients in Europe, is available online and as an app. It makes recommendations to users about when patients should have initial skin screening exams. Those with the most risk — 45% at 5 years — should be screened within 6 months. “We can use [the tool] to triage these cases when we first meet them and get them plugged into the appropriate care,” Dr. Christensen said.
He recommended seeing high-risk patients at least annually. Patients with a prior SCC and a heavy burden of actinic keratosis should be followed more frequently, he said.
In regard to SCC, he highlighted a 2024 study of solid organ transplant recipients that found the risk for a second SCC after a first SCC was 74%, the risk for a third SCC after a second SCC was 83%, and the risk for another SCC after five SCCs was 92%.
Dr. Christensen disclosed relationships with Canfield Scientific Inc. (consulting), Inhibitor Therapeutics (advisory board), and Sol-Gel Technologies Ltd. (grants/research funding).
A version of this article first appeared on Medscape.com.
SAN DIEGO —
because of their suppressed immune systems.“There are over 450,000 people with a solid organ transplant living in the United States. If you do the math, that works out to about 40 organ transplant recipients for every dermatologist, so there’s a lot of them out there for us to take care of,” Sean Christensen, MD, PhD, associate professor of dermatology, Yale University, New Haven, Connecticut, said at the annual meeting of the American Academy of Dermatology (AAD). “If we expand that umbrella to include all types of immunosuppression, that’s over 4 million adults in the US.”
Dr. Christensen encouraged dermatologists to be aware of the varying risks for immunosuppressive drugs and best screening practices for these patients, and to take advantage of a validated skin cancer risk assessment tool for transplant patients.
During his presentation, he highlighted five classes of immunosuppressive drugs and their associated skin cancer risks:
- Calcineurin inhibitors (tacrolimus or cyclosporine), which cause severe immune suppression and pose a severe skin cancer risk. They may also cause gingival hyperplasia and sebaceous hyperplasia.
- Antimetabolites (mycophenolate mofetil or azathioprine), which cause moderate to severe immune suppression and pose a severe skin cancer risk.
- Mammalian target of rapamycin inhibitors (sirolimus or everolimus), which cause severe immune suppression and pose a moderate skin cancer risk. They also impair wound healing.
- Corticosteroids (prednisone), which cause mild to severe immune suppression and pose a minimal skin cancer risk.
- A decoy receptor protein (belatacept), which causes severe immune suppression and poses a mild skin cancer risk.
“Most of our solid-organ transplant recipients will be on both a calcineurin inhibitor and an antimetabolite,” Dr. Christensen said. “In addition to the skin cancer risk associated with immunosuppression, there is an additive risk” that is a direct effect of these medications on the skin. “That means our transplant recipients have a severely and disproportionate increase in skin cancer,” he noted.
Up to half of solid-organ transplant recipients will develop skin cancer, Dr. Christensen said. These patients have a sixfold to 10-fold increased risk for basal cell carcinoma (BCC), a 35- to 65-fold increased risk for squamous cell carcinoma (SCC), a twofold to sevenfold increased risk for melanoma, and a 16- to 100-fold increased risk for Merkel cell carcinoma.
Transplant recipients with SCC, he said, have a twofold to threefold higher risk for metastasis (4%-8% nodal metastasis) and twofold to fivefold higher risk for death (2%-7% mortality) from SCC.
As for other kinds of immunosuppression, HIV positivity, treatment with 6-mercaptopurine or azathioprine (for inflammatory bowel disease and rheumatoid arthritis), and antitumor necrosis factor agents (for psoriasis, inflammatory bowel disease, and rheumatoid arthritis) have been linked in studies to a higher risk for nonmelanoma skin cancer.
Dr. Christensen also highlighted graft-versus-host disease (GVHD). “It does look like there is a disproportionate and increased risk of SCC of the oropharynx and of the skin in patients who have chronic GVHD. This is probably due to a combination of both the immunosuppressive medications that are required but also from chronic and ongoing inflammation in the skin.”
Chronic GVHD has been linked to a 5.3-fold increase in the risk for SCC and a twofold increase in the risk for BCC, he added.
Moreover, new medications for treating GVHD have been linked to an increased risk for SCC, including a 3.2-fold increased risk for SCC associated with ruxolitinib, a Janus kinase (JAK) 1 and JAK2 inhibitor, in a study of patients with polycythemia vera and myelofibrosis; and a case report of SCC in a patient treated with belumosudil, a rho-associated coiled-coil-containing protein kinase-2 kinase inhibitor, for chronic GVHD. Risk for SCC appears to increase based on duration of use with voriconazole, an antifungal, which, he said, is a potent photosynthesizer.
Dr. Christensen also noted the higher risk for infections in immunocompromised patients and added that these patients can develop inflammatory disease despite immunosuppression:
Staphylococcus, Streptococcus, and Dermatophytes are the most common skin pathogens in these patients. There’s a significantly increased risk for reactivation of herpes simplex, varicella-zoster viruses, and cytomegalovirus. Opportunistic and disseminated fungal infections, such as mycobacteria, Candida, histoplasma, cryptococcus, aspergillus, and mucormycosis, can also appear.
More than 80% of transplant recipients develop molluscum and verruca vulgaris/human papillomavirus infection. They may also develop noninfectious inflammatory dermatoses.
Risk Calculator
What can dermatologists do to help transplant patients? Dr. Christensen highlighted the Skin and UV Neoplasia Transplant Risk Assessment Calculator, which predicts skin cancer risk based on points given for race, gender, skin cancer history, age at transplant, and site of transplant.
The tool, validated in a 2023 study of transplant recipients in Europe, is available online and as an app. It makes recommendations to users about when patients should have initial skin screening exams. Those with the most risk — 45% at 5 years — should be screened within 6 months. “We can use [the tool] to triage these cases when we first meet them and get them plugged into the appropriate care,” Dr. Christensen said.
He recommended seeing high-risk patients at least annually. Patients with a prior SCC and a heavy burden of actinic keratosis should be followed more frequently, he said.
In regard to SCC, he highlighted a 2024 study of solid organ transplant recipients that found the risk for a second SCC after a first SCC was 74%, the risk for a third SCC after a second SCC was 83%, and the risk for another SCC after five SCCs was 92%.
Dr. Christensen disclosed relationships with Canfield Scientific Inc. (consulting), Inhibitor Therapeutics (advisory board), and Sol-Gel Technologies Ltd. (grants/research funding).
A version of this article first appeared on Medscape.com.
SAN DIEGO —
because of their suppressed immune systems.“There are over 450,000 people with a solid organ transplant living in the United States. If you do the math, that works out to about 40 organ transplant recipients for every dermatologist, so there’s a lot of them out there for us to take care of,” Sean Christensen, MD, PhD, associate professor of dermatology, Yale University, New Haven, Connecticut, said at the annual meeting of the American Academy of Dermatology (AAD). “If we expand that umbrella to include all types of immunosuppression, that’s over 4 million adults in the US.”
Dr. Christensen encouraged dermatologists to be aware of the varying risks for immunosuppressive drugs and best screening practices for these patients, and to take advantage of a validated skin cancer risk assessment tool for transplant patients.
During his presentation, he highlighted five classes of immunosuppressive drugs and their associated skin cancer risks:
- Calcineurin inhibitors (tacrolimus or cyclosporine), which cause severe immune suppression and pose a severe skin cancer risk. They may also cause gingival hyperplasia and sebaceous hyperplasia.
- Antimetabolites (mycophenolate mofetil or azathioprine), which cause moderate to severe immune suppression and pose a severe skin cancer risk.
- Mammalian target of rapamycin inhibitors (sirolimus or everolimus), which cause severe immune suppression and pose a moderate skin cancer risk. They also impair wound healing.
- Corticosteroids (prednisone), which cause mild to severe immune suppression and pose a minimal skin cancer risk.
- A decoy receptor protein (belatacept), which causes severe immune suppression and poses a mild skin cancer risk.
“Most of our solid-organ transplant recipients will be on both a calcineurin inhibitor and an antimetabolite,” Dr. Christensen said. “In addition to the skin cancer risk associated with immunosuppression, there is an additive risk” that is a direct effect of these medications on the skin. “That means our transplant recipients have a severely and disproportionate increase in skin cancer,” he noted.
Up to half of solid-organ transplant recipients will develop skin cancer, Dr. Christensen said. These patients have a sixfold to 10-fold increased risk for basal cell carcinoma (BCC), a 35- to 65-fold increased risk for squamous cell carcinoma (SCC), a twofold to sevenfold increased risk for melanoma, and a 16- to 100-fold increased risk for Merkel cell carcinoma.
Transplant recipients with SCC, he said, have a twofold to threefold higher risk for metastasis (4%-8% nodal metastasis) and twofold to fivefold higher risk for death (2%-7% mortality) from SCC.
As for other kinds of immunosuppression, HIV positivity, treatment with 6-mercaptopurine or azathioprine (for inflammatory bowel disease and rheumatoid arthritis), and antitumor necrosis factor agents (for psoriasis, inflammatory bowel disease, and rheumatoid arthritis) have been linked in studies to a higher risk for nonmelanoma skin cancer.
Dr. Christensen also highlighted graft-versus-host disease (GVHD). “It does look like there is a disproportionate and increased risk of SCC of the oropharynx and of the skin in patients who have chronic GVHD. This is probably due to a combination of both the immunosuppressive medications that are required but also from chronic and ongoing inflammation in the skin.”
Chronic GVHD has been linked to a 5.3-fold increase in the risk for SCC and a twofold increase in the risk for BCC, he added.
Moreover, new medications for treating GVHD have been linked to an increased risk for SCC, including a 3.2-fold increased risk for SCC associated with ruxolitinib, a Janus kinase (JAK) 1 and JAK2 inhibitor, in a study of patients with polycythemia vera and myelofibrosis; and a case report of SCC in a patient treated with belumosudil, a rho-associated coiled-coil-containing protein kinase-2 kinase inhibitor, for chronic GVHD. Risk for SCC appears to increase based on duration of use with voriconazole, an antifungal, which, he said, is a potent photosynthesizer.
Dr. Christensen also noted the higher risk for infections in immunocompromised patients and added that these patients can develop inflammatory disease despite immunosuppression:
Staphylococcus, Streptococcus, and Dermatophytes are the most common skin pathogens in these patients. There’s a significantly increased risk for reactivation of herpes simplex, varicella-zoster viruses, and cytomegalovirus. Opportunistic and disseminated fungal infections, such as mycobacteria, Candida, histoplasma, cryptococcus, aspergillus, and mucormycosis, can also appear.
More than 80% of transplant recipients develop molluscum and verruca vulgaris/human papillomavirus infection. They may also develop noninfectious inflammatory dermatoses.
Risk Calculator
What can dermatologists do to help transplant patients? Dr. Christensen highlighted the Skin and UV Neoplasia Transplant Risk Assessment Calculator, which predicts skin cancer risk based on points given for race, gender, skin cancer history, age at transplant, and site of transplant.
The tool, validated in a 2023 study of transplant recipients in Europe, is available online and as an app. It makes recommendations to users about when patients should have initial skin screening exams. Those with the most risk — 45% at 5 years — should be screened within 6 months. “We can use [the tool] to triage these cases when we first meet them and get them plugged into the appropriate care,” Dr. Christensen said.
He recommended seeing high-risk patients at least annually. Patients with a prior SCC and a heavy burden of actinic keratosis should be followed more frequently, he said.
In regard to SCC, he highlighted a 2024 study of solid organ transplant recipients that found the risk for a second SCC after a first SCC was 74%, the risk for a third SCC after a second SCC was 83%, and the risk for another SCC after five SCCs was 92%.
Dr. Christensen disclosed relationships with Canfield Scientific Inc. (consulting), Inhibitor Therapeutics (advisory board), and Sol-Gel Technologies Ltd. (grants/research funding).
A version of this article first appeared on Medscape.com.
FROM AAD 2024