User login
Nintedanib slows interstitial lung disease in RA patients
Subgroup analysis from INBUILD trial finds results similar to overall study cohort
In a new subgroup analysis of a previously published multinational trial, the preservation of lung function with nintedanib (Ofev) was about the same in patients with interstitial lung disease related to rheumatoid arthritis (RA-ILD) as it was in patients with other etiologies, according to data presented at the annual European Congress of Rheumatology.
“There was no significant heterogeneity across any of several characteristics we evaluated,” reported Clive Kelly, MBBS, of the Institute of Cellular Medicine at Newcastle University (England).
The INBUILD trial, which enrolled more than 600 patients in 15 countries with a range of fibrosing lung diseases, was published almost 2 years ago. On the primary endpoint of rate of decline in forced vital capacity (FVC), the medians were –80.8 mL per year among those randomized to nintedanib and –187.8 mL per year (P < .001) on placebo.
The INBUILD study provided evidence that fibrosing lung diseases have a common pathobiologic mechanism that can be slowed by targeting intracellular kinases. Nintedanib inhibits several growth factor receptors as well as nonreceptor tyrosine kinases, but its exact mechanism for slowing fibrosing lung diseases remains unclear. Initially approved for, nintedanib received approvals from the FDA for systemic sclerosis–associated ILD in 2019 and for chronic fibrosing ILD with progressive phenotypes in 2020 after being initially approved for the treatment of idiopathic pulmonary fibrosis in 2014.
When asked for comment, Paul F. Dellaripa, MD, an associate professor of medicine in the division of rheumatology, immunology, and allergy at Harvard Medical School, Boston, indicated these data are helpful in considering strategies for RA patients with ILD, but he encouraged collaboration between joint and lung specialists.
“Antifibrotic agents for patients with progressive ILD in autoimmune diseases like RA is a welcome addition to our care of this challenging complication,” said Dr. Dellaripa, who has published frequently on the diagnosis and treatment of lung diseases associated with RA. Yet, treatment must be individualized, he added.
“It will be incumbent for rheumatologists to incorporate lung health as a critical part of patient care and work closely with pulmonologists to consider when to institute antifibrotic therapy in patients with ILD,” he said.
Details of subanalysis
In the RA-ILD subpopulation of 89 patients, there was no further decline in FVC from 24 weeks after randomization to the end of 52 weeks for those on nintedanib, but the decline remained steady over the full course of follow-up among those in the placebo group. At 52 weeks, the decline in the placebo group reached –200 mL at the end of 52 weeks. As a result, the between-group relative reduction in FVC at 52 weeks of 116.7 mL favoring nintedanib over placebo (P < .037) slightly exceeded the 107-mL reduction (P < .001) observed in the overall INBUILD study population.
Among other subgroups the investigators evaluated, outcomes with nintedanib did not differ when patients were split into groups with higher or lower baseline levels of high-sensitivity C-reactive protein, regardless of whether the groups were defined by levels above and below 1 mg/L or 3 mg/L. The same was true for those who were taking nonbiologic disease-modifying antirheumatic drugs or glucocorticoids.
However, for these latter analyses, Dr. Kelly conceded that the differences were based on small numbers of patients and so cannot be considered conclusive.
The adverse event most closely associated with nintedanib in the RA-ILD population was diarrhea, just as in the overall study, and it was more than twice as frequent in the RA-ILD patients receiving the active therapy, compared with placebo (54.8% vs. 25.5%). Nausea was also more common (21.4% vs. 10.6%), and so was decreased appetite (11.9% vs. 2.1%) and weight reduction (9.5% vs. 2.1%).
Lung-related adverse events, such as bronchiolitis (21.4% vs. 17.0%) and dyspnea (11.9% vs. 10.6%), were only slightly more frequent in the nintedanib group. Nasopharyngitis (7.1% vs. 12.8%) was less common. Side effects leading to treatment discontinuation were higher on nintedanib (19.0% vs. 12.8%)
The RA-ILD subgroup represented 13.4% of those randomized in INBUILD. The mean time since diagnosis of RA was about 10 years. More than 60% were smokers or former smokers. At baseline, the mean FVC of predicted was 71%. More than 85% had a usual interstitial pneumonia (UIP) radiologic pattern.
Acute exacerbations and death were not evaluated in the RA-ILD subpopulation, but these were secondary endpoints in the published INBUILD study according to the presence or absence of a UIP-like fibrotic pattern. For the combined endpoint of acute exacerbation of ILD or death, the protection associated with nintedanib approached statistical significance for the population overall (odds ratio, 0.68; 95% confidence interval, 0.46-1.01) and reached significance for those with a UIP pattern (OR, 0.61; 95% CI, 0.38-0.98).
Nintedanib led to lower death rates at 52 weeks in the overall population (8.1% vs. 11.5% with placebo) and in the group with a UIP pattern (9.7% vs. 15.0% with placebo).
Dr. Kelly has financial relationships with multiple pharmaceutical companies, including Boehringer Ingelheim, which provided funding for INBUILD and this subpopulation analysis. Dr. Dellaripa reported financial relationships with Bristol-Myers Squibb and Genentech.
Subgroup analysis from INBUILD trial finds results similar to overall study cohort
Subgroup analysis from INBUILD trial finds results similar to overall study cohort
In a new subgroup analysis of a previously published multinational trial, the preservation of lung function with nintedanib (Ofev) was about the same in patients with interstitial lung disease related to rheumatoid arthritis (RA-ILD) as it was in patients with other etiologies, according to data presented at the annual European Congress of Rheumatology.
“There was no significant heterogeneity across any of several characteristics we evaluated,” reported Clive Kelly, MBBS, of the Institute of Cellular Medicine at Newcastle University (England).
The INBUILD trial, which enrolled more than 600 patients in 15 countries with a range of fibrosing lung diseases, was published almost 2 years ago. On the primary endpoint of rate of decline in forced vital capacity (FVC), the medians were –80.8 mL per year among those randomized to nintedanib and –187.8 mL per year (P < .001) on placebo.
The INBUILD study provided evidence that fibrosing lung diseases have a common pathobiologic mechanism that can be slowed by targeting intracellular kinases. Nintedanib inhibits several growth factor receptors as well as nonreceptor tyrosine kinases, but its exact mechanism for slowing fibrosing lung diseases remains unclear. Initially approved for, nintedanib received approvals from the FDA for systemic sclerosis–associated ILD in 2019 and for chronic fibrosing ILD with progressive phenotypes in 2020 after being initially approved for the treatment of idiopathic pulmonary fibrosis in 2014.
When asked for comment, Paul F. Dellaripa, MD, an associate professor of medicine in the division of rheumatology, immunology, and allergy at Harvard Medical School, Boston, indicated these data are helpful in considering strategies for RA patients with ILD, but he encouraged collaboration between joint and lung specialists.
“Antifibrotic agents for patients with progressive ILD in autoimmune diseases like RA is a welcome addition to our care of this challenging complication,” said Dr. Dellaripa, who has published frequently on the diagnosis and treatment of lung diseases associated with RA. Yet, treatment must be individualized, he added.
“It will be incumbent for rheumatologists to incorporate lung health as a critical part of patient care and work closely with pulmonologists to consider when to institute antifibrotic therapy in patients with ILD,” he said.
Details of subanalysis
In the RA-ILD subpopulation of 89 patients, there was no further decline in FVC from 24 weeks after randomization to the end of 52 weeks for those on nintedanib, but the decline remained steady over the full course of follow-up among those in the placebo group. At 52 weeks, the decline in the placebo group reached –200 mL at the end of 52 weeks. As a result, the between-group relative reduction in FVC at 52 weeks of 116.7 mL favoring nintedanib over placebo (P < .037) slightly exceeded the 107-mL reduction (P < .001) observed in the overall INBUILD study population.
Among other subgroups the investigators evaluated, outcomes with nintedanib did not differ when patients were split into groups with higher or lower baseline levels of high-sensitivity C-reactive protein, regardless of whether the groups were defined by levels above and below 1 mg/L or 3 mg/L. The same was true for those who were taking nonbiologic disease-modifying antirheumatic drugs or glucocorticoids.
However, for these latter analyses, Dr. Kelly conceded that the differences were based on small numbers of patients and so cannot be considered conclusive.
The adverse event most closely associated with nintedanib in the RA-ILD population was diarrhea, just as in the overall study, and it was more than twice as frequent in the RA-ILD patients receiving the active therapy, compared with placebo (54.8% vs. 25.5%). Nausea was also more common (21.4% vs. 10.6%), and so was decreased appetite (11.9% vs. 2.1%) and weight reduction (9.5% vs. 2.1%).
Lung-related adverse events, such as bronchiolitis (21.4% vs. 17.0%) and dyspnea (11.9% vs. 10.6%), were only slightly more frequent in the nintedanib group. Nasopharyngitis (7.1% vs. 12.8%) was less common. Side effects leading to treatment discontinuation were higher on nintedanib (19.0% vs. 12.8%)
The RA-ILD subgroup represented 13.4% of those randomized in INBUILD. The mean time since diagnosis of RA was about 10 years. More than 60% were smokers or former smokers. At baseline, the mean FVC of predicted was 71%. More than 85% had a usual interstitial pneumonia (UIP) radiologic pattern.
Acute exacerbations and death were not evaluated in the RA-ILD subpopulation, but these were secondary endpoints in the published INBUILD study according to the presence or absence of a UIP-like fibrotic pattern. For the combined endpoint of acute exacerbation of ILD or death, the protection associated with nintedanib approached statistical significance for the population overall (odds ratio, 0.68; 95% confidence interval, 0.46-1.01) and reached significance for those with a UIP pattern (OR, 0.61; 95% CI, 0.38-0.98).
Nintedanib led to lower death rates at 52 weeks in the overall population (8.1% vs. 11.5% with placebo) and in the group with a UIP pattern (9.7% vs. 15.0% with placebo).
Dr. Kelly has financial relationships with multiple pharmaceutical companies, including Boehringer Ingelheim, which provided funding for INBUILD and this subpopulation analysis. Dr. Dellaripa reported financial relationships with Bristol-Myers Squibb and Genentech.
In a new subgroup analysis of a previously published multinational trial, the preservation of lung function with nintedanib (Ofev) was about the same in patients with interstitial lung disease related to rheumatoid arthritis (RA-ILD) as it was in patients with other etiologies, according to data presented at the annual European Congress of Rheumatology.
“There was no significant heterogeneity across any of several characteristics we evaluated,” reported Clive Kelly, MBBS, of the Institute of Cellular Medicine at Newcastle University (England).
The INBUILD trial, which enrolled more than 600 patients in 15 countries with a range of fibrosing lung diseases, was published almost 2 years ago. On the primary endpoint of rate of decline in forced vital capacity (FVC), the medians were –80.8 mL per year among those randomized to nintedanib and –187.8 mL per year (P < .001) on placebo.
The INBUILD study provided evidence that fibrosing lung diseases have a common pathobiologic mechanism that can be slowed by targeting intracellular kinases. Nintedanib inhibits several growth factor receptors as well as nonreceptor tyrosine kinases, but its exact mechanism for slowing fibrosing lung diseases remains unclear. Initially approved for, nintedanib received approvals from the FDA for systemic sclerosis–associated ILD in 2019 and for chronic fibrosing ILD with progressive phenotypes in 2020 after being initially approved for the treatment of idiopathic pulmonary fibrosis in 2014.
When asked for comment, Paul F. Dellaripa, MD, an associate professor of medicine in the division of rheumatology, immunology, and allergy at Harvard Medical School, Boston, indicated these data are helpful in considering strategies for RA patients with ILD, but he encouraged collaboration between joint and lung specialists.
“Antifibrotic agents for patients with progressive ILD in autoimmune diseases like RA is a welcome addition to our care of this challenging complication,” said Dr. Dellaripa, who has published frequently on the diagnosis and treatment of lung diseases associated with RA. Yet, treatment must be individualized, he added.
“It will be incumbent for rheumatologists to incorporate lung health as a critical part of patient care and work closely with pulmonologists to consider when to institute antifibrotic therapy in patients with ILD,” he said.
Details of subanalysis
In the RA-ILD subpopulation of 89 patients, there was no further decline in FVC from 24 weeks after randomization to the end of 52 weeks for those on nintedanib, but the decline remained steady over the full course of follow-up among those in the placebo group. At 52 weeks, the decline in the placebo group reached –200 mL at the end of 52 weeks. As a result, the between-group relative reduction in FVC at 52 weeks of 116.7 mL favoring nintedanib over placebo (P < .037) slightly exceeded the 107-mL reduction (P < .001) observed in the overall INBUILD study population.
Among other subgroups the investigators evaluated, outcomes with nintedanib did not differ when patients were split into groups with higher or lower baseline levels of high-sensitivity C-reactive protein, regardless of whether the groups were defined by levels above and below 1 mg/L or 3 mg/L. The same was true for those who were taking nonbiologic disease-modifying antirheumatic drugs or glucocorticoids.
However, for these latter analyses, Dr. Kelly conceded that the differences were based on small numbers of patients and so cannot be considered conclusive.
The adverse event most closely associated with nintedanib in the RA-ILD population was diarrhea, just as in the overall study, and it was more than twice as frequent in the RA-ILD patients receiving the active therapy, compared with placebo (54.8% vs. 25.5%). Nausea was also more common (21.4% vs. 10.6%), and so was decreased appetite (11.9% vs. 2.1%) and weight reduction (9.5% vs. 2.1%).
Lung-related adverse events, such as bronchiolitis (21.4% vs. 17.0%) and dyspnea (11.9% vs. 10.6%), were only slightly more frequent in the nintedanib group. Nasopharyngitis (7.1% vs. 12.8%) was less common. Side effects leading to treatment discontinuation were higher on nintedanib (19.0% vs. 12.8%)
The RA-ILD subgroup represented 13.4% of those randomized in INBUILD. The mean time since diagnosis of RA was about 10 years. More than 60% were smokers or former smokers. At baseline, the mean FVC of predicted was 71%. More than 85% had a usual interstitial pneumonia (UIP) radiologic pattern.
Acute exacerbations and death were not evaluated in the RA-ILD subpopulation, but these were secondary endpoints in the published INBUILD study according to the presence or absence of a UIP-like fibrotic pattern. For the combined endpoint of acute exacerbation of ILD or death, the protection associated with nintedanib approached statistical significance for the population overall (odds ratio, 0.68; 95% confidence interval, 0.46-1.01) and reached significance for those with a UIP pattern (OR, 0.61; 95% CI, 0.38-0.98).
Nintedanib led to lower death rates at 52 weeks in the overall population (8.1% vs. 11.5% with placebo) and in the group with a UIP pattern (9.7% vs. 15.0% with placebo).
Dr. Kelly has financial relationships with multiple pharmaceutical companies, including Boehringer Ingelheim, which provided funding for INBUILD and this subpopulation analysis. Dr. Dellaripa reported financial relationships with Bristol-Myers Squibb and Genentech.
FROM THE EULAR 2021 CONGRESS
Medical licensing questions continue to violate ADA
With the COVID-19 pandemic, already high rates of suicide, depression, and burnout among physicians became even more acute. Yet, 3 years after the Federation of State Medical Boards issued recommendations on what questions about mental health status license applications should – or mostly should not – include, only North Carolina fully complies with all four recommendations, and most states comply with two or fewer, a study of state medical board applications has found (JAMA. 2021 May 18;325[19];2017-8).
Questions about mental health history or “its hypothetical effect on competency,” violate the Americans with Disabilities Act, the study authors stated. In a research letter to JAMA, the authors also reported that five state boards do not comply with any of the FSMB recommendations. Twenty-four states comply with three of the four recommendations.
Overall, the mean consistency score was 2.1, which means state medical licensing applications typically run afoul of the Americans With Disabilities Act when it comes to mental health history of applicants.
“No one should ever wonder, ‘Will I lose my job, or should I get help?’ ” said co–senior author Jessica A. Gold, MD, MS, a psychiatrist at Washington University in St. Louis. “This should absolutely never be a question on someone’s mind. And the fact that it is, in medicine, is a problem that needs to be solved. I hope that people are beginning to see that, and we can make a change to get people the help they need before it is too late.”
High rates of depression, suicide
She noted that before COVID-19, physicians already had higher rates of depression, burnout, and suicide than the general population. “Over COVID-19, it has become clear that the mental health of physicians has become additionally compounded,” Dr. Gold said.
One study found that physicians had a 44% higher rate of suicide (PLoS One. 2019 Dec;14[12]:e0226361), but they’re notoriously reluctant to seek out mental health care. A 2017 study reported that 40% of physicians would be reluctant to seek mental health care because of concerns about their licensure (Mayo Clin Proc. 2017;92[10]:1486-93).
As the pandemic went on, Dr. Gold and her colleagues decided to study whether state boards had improved their compliance with the FSMB recommendations issued in 2018. Those recommendations include these four limitations regarding questions about mental health conditions on license applications:
- Include only when they result in impairment.
- Include only when the mental health conditions are current – that is, when they’ve occurred within the past 2 years.
- Provide safe haven nonreporting – that is, allow physicians to not report previously diagnosed and treated mental health conditions if they’re being monitored and are in good standing with a physician health program.
- Include supportive or nonjudgmental language about seeking mental health care.
The study considered board applications that had questions about mental health status as consistent with the first three recommendations. Seventeen states complied.
Thirty-nine state boards complied with the first recommendation regarding impairment; 41 with the second recommendation about near-term history; 25 with safe-haven nonreporting. Only eight states were consistent with the recommendation on supportive language.
The ADA limits inquiries about an applicant’s impairment to only current conditions. In a 2017 study, only 21 state boards had limited questions to current impairment. “This is a significant improvement, but this still means the rest of the states are violating an actual law,” Dr. Gold said. “Another plus is that 17 states asked no questions at all that could require mental health disclosure. This, too is significant because it highlights change in thinking.”
But still, the fact that five states didn’t comply with any recommendation and only one followed all of them is “utterly unacceptable,” Dr. Gold said. “Instead, we should have universal adoption of FSMB recommendations.”
Time to remove stigma
Michael F. Myers, MD, a clinical psychiatrist at the State University of New York, Brooklyn, said removing the stigma of seeking help for mental health conditions is especially important for physicians. He’s written several books about physician mental health, including his latest, “Becoming a Doctor’s Doctor: A Memoir.”
“I would say at least 15% of the families that I interviewed who lost a physician loved one to suicide have said the doctor was petrified of going for professional help because of fears of what this could do to their medical license,” he said. “It is extremely important that those licensing questions will be either brought up to speed, or – the ones that are clearly violating the ADA – that they be removed.”
Applications for hospital privileges can also run afoul of the same ADA standard, Dr. Myers added. “Physicians have told me that when they go to get medical privileges at a medical center, they get asked all kinds of questions that are outdated, that are intrusive, that violate the ADA,” he said.
Credentialing is another area that Dr. Gold and her colleagues are interested in studying, she said. “Sometimes the licensing applications can be fine, but then the hospital someone is applying to work at can ask the same illegal questions anyway,” she said. “So it doesn’t matter that the state fixed the problem because the hospital asked them anyway. You feel your job is at risk in the same way, so you still don’t get help.”
Dr. Gold and Dr. Myers have no relevant financial relationships to disclose.
With the COVID-19 pandemic, already high rates of suicide, depression, and burnout among physicians became even more acute. Yet, 3 years after the Federation of State Medical Boards issued recommendations on what questions about mental health status license applications should – or mostly should not – include, only North Carolina fully complies with all four recommendations, and most states comply with two or fewer, a study of state medical board applications has found (JAMA. 2021 May 18;325[19];2017-8).
Questions about mental health history or “its hypothetical effect on competency,” violate the Americans with Disabilities Act, the study authors stated. In a research letter to JAMA, the authors also reported that five state boards do not comply with any of the FSMB recommendations. Twenty-four states comply with three of the four recommendations.
Overall, the mean consistency score was 2.1, which means state medical licensing applications typically run afoul of the Americans With Disabilities Act when it comes to mental health history of applicants.
“No one should ever wonder, ‘Will I lose my job, or should I get help?’ ” said co–senior author Jessica A. Gold, MD, MS, a psychiatrist at Washington University in St. Louis. “This should absolutely never be a question on someone’s mind. And the fact that it is, in medicine, is a problem that needs to be solved. I hope that people are beginning to see that, and we can make a change to get people the help they need before it is too late.”
High rates of depression, suicide
She noted that before COVID-19, physicians already had higher rates of depression, burnout, and suicide than the general population. “Over COVID-19, it has become clear that the mental health of physicians has become additionally compounded,” Dr. Gold said.
One study found that physicians had a 44% higher rate of suicide (PLoS One. 2019 Dec;14[12]:e0226361), but they’re notoriously reluctant to seek out mental health care. A 2017 study reported that 40% of physicians would be reluctant to seek mental health care because of concerns about their licensure (Mayo Clin Proc. 2017;92[10]:1486-93).
As the pandemic went on, Dr. Gold and her colleagues decided to study whether state boards had improved their compliance with the FSMB recommendations issued in 2018. Those recommendations include these four limitations regarding questions about mental health conditions on license applications:
- Include only when they result in impairment.
- Include only when the mental health conditions are current – that is, when they’ve occurred within the past 2 years.
- Provide safe haven nonreporting – that is, allow physicians to not report previously diagnosed and treated mental health conditions if they’re being monitored and are in good standing with a physician health program.
- Include supportive or nonjudgmental language about seeking mental health care.
The study considered board applications that had questions about mental health status as consistent with the first three recommendations. Seventeen states complied.
Thirty-nine state boards complied with the first recommendation regarding impairment; 41 with the second recommendation about near-term history; 25 with safe-haven nonreporting. Only eight states were consistent with the recommendation on supportive language.
The ADA limits inquiries about an applicant’s impairment to only current conditions. In a 2017 study, only 21 state boards had limited questions to current impairment. “This is a significant improvement, but this still means the rest of the states are violating an actual law,” Dr. Gold said. “Another plus is that 17 states asked no questions at all that could require mental health disclosure. This, too is significant because it highlights change in thinking.”
But still, the fact that five states didn’t comply with any recommendation and only one followed all of them is “utterly unacceptable,” Dr. Gold said. “Instead, we should have universal adoption of FSMB recommendations.”
Time to remove stigma
Michael F. Myers, MD, a clinical psychiatrist at the State University of New York, Brooklyn, said removing the stigma of seeking help for mental health conditions is especially important for physicians. He’s written several books about physician mental health, including his latest, “Becoming a Doctor’s Doctor: A Memoir.”
“I would say at least 15% of the families that I interviewed who lost a physician loved one to suicide have said the doctor was petrified of going for professional help because of fears of what this could do to their medical license,” he said. “It is extremely important that those licensing questions will be either brought up to speed, or – the ones that are clearly violating the ADA – that they be removed.”
Applications for hospital privileges can also run afoul of the same ADA standard, Dr. Myers added. “Physicians have told me that when they go to get medical privileges at a medical center, they get asked all kinds of questions that are outdated, that are intrusive, that violate the ADA,” he said.
Credentialing is another area that Dr. Gold and her colleagues are interested in studying, she said. “Sometimes the licensing applications can be fine, but then the hospital someone is applying to work at can ask the same illegal questions anyway,” she said. “So it doesn’t matter that the state fixed the problem because the hospital asked them anyway. You feel your job is at risk in the same way, so you still don’t get help.”
Dr. Gold and Dr. Myers have no relevant financial relationships to disclose.
With the COVID-19 pandemic, already high rates of suicide, depression, and burnout among physicians became even more acute. Yet, 3 years after the Federation of State Medical Boards issued recommendations on what questions about mental health status license applications should – or mostly should not – include, only North Carolina fully complies with all four recommendations, and most states comply with two or fewer, a study of state medical board applications has found (JAMA. 2021 May 18;325[19];2017-8).
Questions about mental health history or “its hypothetical effect on competency,” violate the Americans with Disabilities Act, the study authors stated. In a research letter to JAMA, the authors also reported that five state boards do not comply with any of the FSMB recommendations. Twenty-four states comply with three of the four recommendations.
Overall, the mean consistency score was 2.1, which means state medical licensing applications typically run afoul of the Americans With Disabilities Act when it comes to mental health history of applicants.
“No one should ever wonder, ‘Will I lose my job, or should I get help?’ ” said co–senior author Jessica A. Gold, MD, MS, a psychiatrist at Washington University in St. Louis. “This should absolutely never be a question on someone’s mind. And the fact that it is, in medicine, is a problem that needs to be solved. I hope that people are beginning to see that, and we can make a change to get people the help they need before it is too late.”
High rates of depression, suicide
She noted that before COVID-19, physicians already had higher rates of depression, burnout, and suicide than the general population. “Over COVID-19, it has become clear that the mental health of physicians has become additionally compounded,” Dr. Gold said.
One study found that physicians had a 44% higher rate of suicide (PLoS One. 2019 Dec;14[12]:e0226361), but they’re notoriously reluctant to seek out mental health care. A 2017 study reported that 40% of physicians would be reluctant to seek mental health care because of concerns about their licensure (Mayo Clin Proc. 2017;92[10]:1486-93).
As the pandemic went on, Dr. Gold and her colleagues decided to study whether state boards had improved their compliance with the FSMB recommendations issued in 2018. Those recommendations include these four limitations regarding questions about mental health conditions on license applications:
- Include only when they result in impairment.
- Include only when the mental health conditions are current – that is, when they’ve occurred within the past 2 years.
- Provide safe haven nonreporting – that is, allow physicians to not report previously diagnosed and treated mental health conditions if they’re being monitored and are in good standing with a physician health program.
- Include supportive or nonjudgmental language about seeking mental health care.
The study considered board applications that had questions about mental health status as consistent with the first three recommendations. Seventeen states complied.
Thirty-nine state boards complied with the first recommendation regarding impairment; 41 with the second recommendation about near-term history; 25 with safe-haven nonreporting. Only eight states were consistent with the recommendation on supportive language.
The ADA limits inquiries about an applicant’s impairment to only current conditions. In a 2017 study, only 21 state boards had limited questions to current impairment. “This is a significant improvement, but this still means the rest of the states are violating an actual law,” Dr. Gold said. “Another plus is that 17 states asked no questions at all that could require mental health disclosure. This, too is significant because it highlights change in thinking.”
But still, the fact that five states didn’t comply with any recommendation and only one followed all of them is “utterly unacceptable,” Dr. Gold said. “Instead, we should have universal adoption of FSMB recommendations.”
Time to remove stigma
Michael F. Myers, MD, a clinical psychiatrist at the State University of New York, Brooklyn, said removing the stigma of seeking help for mental health conditions is especially important for physicians. He’s written several books about physician mental health, including his latest, “Becoming a Doctor’s Doctor: A Memoir.”
“I would say at least 15% of the families that I interviewed who lost a physician loved one to suicide have said the doctor was petrified of going for professional help because of fears of what this could do to their medical license,” he said. “It is extremely important that those licensing questions will be either brought up to speed, or – the ones that are clearly violating the ADA – that they be removed.”
Applications for hospital privileges can also run afoul of the same ADA standard, Dr. Myers added. “Physicians have told me that when they go to get medical privileges at a medical center, they get asked all kinds of questions that are outdated, that are intrusive, that violate the ADA,” he said.
Credentialing is another area that Dr. Gold and her colleagues are interested in studying, she said. “Sometimes the licensing applications can be fine, but then the hospital someone is applying to work at can ask the same illegal questions anyway,” she said. “So it doesn’t matter that the state fixed the problem because the hospital asked them anyway. You feel your job is at risk in the same way, so you still don’t get help.”
Dr. Gold and Dr. Myers have no relevant financial relationships to disclose.
FROM JAMA
IL-6 levels predict distant breast cancer recurrence
The inflammatory cytokine interleukin 6 may be a biomarker for distant recurrence of breast cancer among patients treated for stage II-III HER2-negative disease, investigators have found.
In a case-control study of 498 women with breast cancer treated with surgery and adjuvant chemotherapy, as well as endocrine therapy for women with estrogen receptor (ER)–positive tumors, those with higher serum levels of IL-6 at diagnosis had a significantly greater risk for disease recurrence than women with lower levels of the cytokine, Joseph A. Sparano, MD, from the Albert Einstein College of Medicine and Montefiore Medical Center, New York, and colleagues reported.
“This analysis provides level 1B evidence indicating that higher levels of the cytokine IL-6 at diagnosis are associated with a significantly higher distant recurrence risk in high-risk stage II-III breast cancer despite optimal adjuvant systemic therapy,” they wrote in a study presented in a poster discussion session at the American Society of Clinical Oncology Annual Meeting.(Abstract 520)
In an interview, Dr. Sparano said that their findings first need to be validated in a larger study.
“When validated, I think the other key issue is to try to understand what the best cut point for identifying high risk is, “ he said.
If further studies confirm that higher IL-6 levels are prognostic for worse outcomes, it might be possible to use levels of the cytokine as a biomarker to predict for therapies targeting the IL-6/Janus kinase/STAT3 pathway.
“There are trials ongoing testing IL-6 antibodies in combination chemotherapy, and this could be a rational biomarker to identify which patients would be more likely to benefit from that approach,” he said.
Systemic inflammation
Systemic inflammation is suspected as a contributing factor to cancer progression and disease recurrence, Dr. Sparano and colleagues noted.
To test their hypothesis that inflammatory cytokines and/or chemokines could be associated with distant recurrence, they conducted a case-control study with 249 matched pairs of patients enrolled in a phase 3 trial of adjuvant chemotherapy for lymph-node positive and high-risk lymph-node negative breast cancer (NCT00433511).
The patients all had surgery and adjuvant chemotherapy with doxorubicin, cyclophosphamide, and paclitaxel with or without bevacizumab, and endocrine therapy for patients whose tumors were ER positive.
They used propensity score matching to pair each patient with distant recurrence to one without, with covariates including post versus premenopausal or perimenopausal status, estrogen and/or progesterone receptor positivity, tumor size (less than 2 cm, greater than 2-5 cm, or greater than 5 cm) nodal status, and grade.
The only biomarker that met the prespecified boundary for statistical significance (P < .0014) was IL-6, with a hazard ratio for distant recurrence of 1.37 (P = .0006).
The median and mean values for IL-6 were 0.95 and 7.5 pg/mL, respectively
Other substances associated with distant recurrence (with a two-sided P value < .05) were macrophage-derived chemokine/CCL22 (HR, 1.90; P = .0098), IL-17A, a T-helper cell inflammatory cytokine (HR, 1.36; P = .0052), and the cytokine vascular endothelial growth factor A (VEGF-A, HR, 1.13; P = 0.037).
There was no statistical interaction between VEGF-A levels and the benefit of bevacizumab.
Prognostic value, not clinical utility
“This is a nice abstract. It looks at inflammatory cytokines and provides evidence that inflammatory cytokines, particularly IL-6, could have a prognostic role in predicting risk of recurrence in HER2-negative disease, and the team did a very nice job in multivariate analysis looking at different factors,” said Aditya Bardia, MD, MPH, from the Mass General Cancer Center in Boston, the invited discussant for the study.*
In an interview, Dr. Bardia said that the finding “provides prognostic value, but does not provide clinical utility. It’s unclear if we used this assay and it identified that a patient was at high risk of recurrence whether we could change that. Is there any intervention that could be done to potentially alter the course of disease, alter the natural history? That’s unknown.”
He agreed with Dr. Sparano and colleagues that validation of the finding was still needed, ideally in a prospective or retrospective cohort study.
The study was supported by grants from the National Cancer Institute, Komen Foundation, and Breast Cancer Research Foundation. Dr. Sparano disclosed relationships with multiple companies. Dr. Bardia disclosed a consulting or advisory role and research funding to his institution from multiple companies.
*Correction, 6/4/21: An earlier version of this article misstated Dr. Bardia's name.
The inflammatory cytokine interleukin 6 may be a biomarker for distant recurrence of breast cancer among patients treated for stage II-III HER2-negative disease, investigators have found.
In a case-control study of 498 women with breast cancer treated with surgery and adjuvant chemotherapy, as well as endocrine therapy for women with estrogen receptor (ER)–positive tumors, those with higher serum levels of IL-6 at diagnosis had a significantly greater risk for disease recurrence than women with lower levels of the cytokine, Joseph A. Sparano, MD, from the Albert Einstein College of Medicine and Montefiore Medical Center, New York, and colleagues reported.
“This analysis provides level 1B evidence indicating that higher levels of the cytokine IL-6 at diagnosis are associated with a significantly higher distant recurrence risk in high-risk stage II-III breast cancer despite optimal adjuvant systemic therapy,” they wrote in a study presented in a poster discussion session at the American Society of Clinical Oncology Annual Meeting.(Abstract 520)
In an interview, Dr. Sparano said that their findings first need to be validated in a larger study.
“When validated, I think the other key issue is to try to understand what the best cut point for identifying high risk is, “ he said.
If further studies confirm that higher IL-6 levels are prognostic for worse outcomes, it might be possible to use levels of the cytokine as a biomarker to predict for therapies targeting the IL-6/Janus kinase/STAT3 pathway.
“There are trials ongoing testing IL-6 antibodies in combination chemotherapy, and this could be a rational biomarker to identify which patients would be more likely to benefit from that approach,” he said.
Systemic inflammation
Systemic inflammation is suspected as a contributing factor to cancer progression and disease recurrence, Dr. Sparano and colleagues noted.
To test their hypothesis that inflammatory cytokines and/or chemokines could be associated with distant recurrence, they conducted a case-control study with 249 matched pairs of patients enrolled in a phase 3 trial of adjuvant chemotherapy for lymph-node positive and high-risk lymph-node negative breast cancer (NCT00433511).
The patients all had surgery and adjuvant chemotherapy with doxorubicin, cyclophosphamide, and paclitaxel with or without bevacizumab, and endocrine therapy for patients whose tumors were ER positive.
They used propensity score matching to pair each patient with distant recurrence to one without, with covariates including post versus premenopausal or perimenopausal status, estrogen and/or progesterone receptor positivity, tumor size (less than 2 cm, greater than 2-5 cm, or greater than 5 cm) nodal status, and grade.
The only biomarker that met the prespecified boundary for statistical significance (P < .0014) was IL-6, with a hazard ratio for distant recurrence of 1.37 (P = .0006).
The median and mean values for IL-6 were 0.95 and 7.5 pg/mL, respectively
Other substances associated with distant recurrence (with a two-sided P value < .05) were macrophage-derived chemokine/CCL22 (HR, 1.90; P = .0098), IL-17A, a T-helper cell inflammatory cytokine (HR, 1.36; P = .0052), and the cytokine vascular endothelial growth factor A (VEGF-A, HR, 1.13; P = 0.037).
There was no statistical interaction between VEGF-A levels and the benefit of bevacizumab.
Prognostic value, not clinical utility
“This is a nice abstract. It looks at inflammatory cytokines and provides evidence that inflammatory cytokines, particularly IL-6, could have a prognostic role in predicting risk of recurrence in HER2-negative disease, and the team did a very nice job in multivariate analysis looking at different factors,” said Aditya Bardia, MD, MPH, from the Mass General Cancer Center in Boston, the invited discussant for the study.*
In an interview, Dr. Bardia said that the finding “provides prognostic value, but does not provide clinical utility. It’s unclear if we used this assay and it identified that a patient was at high risk of recurrence whether we could change that. Is there any intervention that could be done to potentially alter the course of disease, alter the natural history? That’s unknown.”
He agreed with Dr. Sparano and colleagues that validation of the finding was still needed, ideally in a prospective or retrospective cohort study.
The study was supported by grants from the National Cancer Institute, Komen Foundation, and Breast Cancer Research Foundation. Dr. Sparano disclosed relationships with multiple companies. Dr. Bardia disclosed a consulting or advisory role and research funding to his institution from multiple companies.
*Correction, 6/4/21: An earlier version of this article misstated Dr. Bardia's name.
The inflammatory cytokine interleukin 6 may be a biomarker for distant recurrence of breast cancer among patients treated for stage II-III HER2-negative disease, investigators have found.
In a case-control study of 498 women with breast cancer treated with surgery and adjuvant chemotherapy, as well as endocrine therapy for women with estrogen receptor (ER)–positive tumors, those with higher serum levels of IL-6 at diagnosis had a significantly greater risk for disease recurrence than women with lower levels of the cytokine, Joseph A. Sparano, MD, from the Albert Einstein College of Medicine and Montefiore Medical Center, New York, and colleagues reported.
“This analysis provides level 1B evidence indicating that higher levels of the cytokine IL-6 at diagnosis are associated with a significantly higher distant recurrence risk in high-risk stage II-III breast cancer despite optimal adjuvant systemic therapy,” they wrote in a study presented in a poster discussion session at the American Society of Clinical Oncology Annual Meeting.(Abstract 520)
In an interview, Dr. Sparano said that their findings first need to be validated in a larger study.
“When validated, I think the other key issue is to try to understand what the best cut point for identifying high risk is, “ he said.
If further studies confirm that higher IL-6 levels are prognostic for worse outcomes, it might be possible to use levels of the cytokine as a biomarker to predict for therapies targeting the IL-6/Janus kinase/STAT3 pathway.
“There are trials ongoing testing IL-6 antibodies in combination chemotherapy, and this could be a rational biomarker to identify which patients would be more likely to benefit from that approach,” he said.
Systemic inflammation
Systemic inflammation is suspected as a contributing factor to cancer progression and disease recurrence, Dr. Sparano and colleagues noted.
To test their hypothesis that inflammatory cytokines and/or chemokines could be associated with distant recurrence, they conducted a case-control study with 249 matched pairs of patients enrolled in a phase 3 trial of adjuvant chemotherapy for lymph-node positive and high-risk lymph-node negative breast cancer (NCT00433511).
The patients all had surgery and adjuvant chemotherapy with doxorubicin, cyclophosphamide, and paclitaxel with or without bevacizumab, and endocrine therapy for patients whose tumors were ER positive.
They used propensity score matching to pair each patient with distant recurrence to one without, with covariates including post versus premenopausal or perimenopausal status, estrogen and/or progesterone receptor positivity, tumor size (less than 2 cm, greater than 2-5 cm, or greater than 5 cm) nodal status, and grade.
The only biomarker that met the prespecified boundary for statistical significance (P < .0014) was IL-6, with a hazard ratio for distant recurrence of 1.37 (P = .0006).
The median and mean values for IL-6 were 0.95 and 7.5 pg/mL, respectively
Other substances associated with distant recurrence (with a two-sided P value < .05) were macrophage-derived chemokine/CCL22 (HR, 1.90; P = .0098), IL-17A, a T-helper cell inflammatory cytokine (HR, 1.36; P = .0052), and the cytokine vascular endothelial growth factor A (VEGF-A, HR, 1.13; P = 0.037).
There was no statistical interaction between VEGF-A levels and the benefit of bevacizumab.
Prognostic value, not clinical utility
“This is a nice abstract. It looks at inflammatory cytokines and provides evidence that inflammatory cytokines, particularly IL-6, could have a prognostic role in predicting risk of recurrence in HER2-negative disease, and the team did a very nice job in multivariate analysis looking at different factors,” said Aditya Bardia, MD, MPH, from the Mass General Cancer Center in Boston, the invited discussant for the study.*
In an interview, Dr. Bardia said that the finding “provides prognostic value, but does not provide clinical utility. It’s unclear if we used this assay and it identified that a patient was at high risk of recurrence whether we could change that. Is there any intervention that could be done to potentially alter the course of disease, alter the natural history? That’s unknown.”
He agreed with Dr. Sparano and colleagues that validation of the finding was still needed, ideally in a prospective or retrospective cohort study.
The study was supported by grants from the National Cancer Institute, Komen Foundation, and Breast Cancer Research Foundation. Dr. Sparano disclosed relationships with multiple companies. Dr. Bardia disclosed a consulting or advisory role and research funding to his institution from multiple companies.
*Correction, 6/4/21: An earlier version of this article misstated Dr. Bardia's name.
FROM ASCO 2021
A1c below prediabetes cutoff linked to subclinical atherosclerosis
, according to an analysis of data on almost 4,000 middle-aged individuals.
“If one looks at the incidence of generalized subclinical atherosclerosis, we are not talking small numbers,” senior study author Valentin Fuster, MD, PhD, said in an interview. “We are talking about between 45% and 82% of this middle-age population that already has atherosclerotic disease subclinically.
“Actually,” he added, “the disease was extensive in 5%-30% of these individuals of middle age.”
The study included 3,973 participants from the Progression of Early Subclinical Atherosclerosis study who did not have diabetes. A1c showed an association with the prevalence and multiterritorial extent of subclinical atherosclerosis as measured by two-dimensional ultrasound and coronary artery calcium score (CACS; P < .001). For example, those with A1c above 6.1% (133 participants) had a 33.1% rate of generalized subclinical atherosclerosis, compared with 4.9% for those with A1c below 4.8% (243), the lowest-score group in the study.
Patients in the subprediabetes band, between 5.0% and 5.5%, had significantly higher rates of generalized subclinical atherosclerosis than did the lowest-score group: 8% in the 4.9%-5.0% group (375 participants); 9.9% in the 5.1%-5.2% range (687); 10.3% in the 5.3%-5.4% group (928); and 11.5% in the 5.5%-5.6% group (842).
Those in the 5.1%-5.2% and 5/3%-5.4% A1c groups had a 27% greater chance of having subclinical atherosclerosis, while those in the 5.5%-5.6% group had a 36% greater risk, according to an odds ratio analysis adjusted for established cardiovascular risk factors. The risks were even higher for patients with prediabetes, the researchers reported in the Journal of the American College of Cardiology.
A call for earlier intervention
Notably, the study found that fasting plasma glucose testing did not yield a similar association between A1c and atherosclerosis.
“The message is that we all talk about people when they are close to the development of cardiovascular events, and here we are talking about people who we should pay attention to much earlier,” said Dr. Fuster, physician-in-chief at Icahn School of Medicine at Mount Sinai in New York and director of the National Center for Cardiovascular Investigation in Madrid, where the observational study originated said. “People should be sensitized to HbA1c much more than they would’ve been in the past, and I think this study actually validates that.”
Christie Ballantyne, MD, noted in an interview that these findings support the utility of A1c for predicting CVD risk.
“I think more and more we should be ordering a HbA1c” during routine physical exams, Dr. Ballantyne said. “You don’t have to be obese to get it; there are lots of people, maybe they’re slightly overweight. It’s a reasonable test to be getting when you get to middle age and older to get an idea for assessing for both developing diabetes and also the presence of atherosclerosis and the risk for having cardiovascular events.”
Dr. Ballantyne, chief of cardiology at Baylor College of Medicine and director of cardiovascular disease prevention at Methodist DeBakey Heart Center in Houston, coauthored an editorial comment on the study.
Clinicians typically start to manage CVD and diabetes risk “late in the process,” Dr. Ballantyne said. This study suggested that earlier use of antidiabetes therapies, namely peptide-1 agonists and semisynthetic glucagon-like peptide-2 inhibitors, may be warranted in patients with intermediate risk of CVD.
“It’s just more data for the rationale that, perhaps we could end up doing trials to show we can take high-risk people and prevent them from getting both heart disease and diabetes,” Dr. Ballantyne added. “Could we start a little earlier with better precision?”
These finding don’t yet call for a change in how cardiologists and endocrinologists manage patients on the cusp of prediabetes, said Paul S. Jellinger, MD, of Hollywood, Fla., and a professor at the University of Miami. “The endpoint of subclinical atherosclerosis does not necessarily translate into the harder endpoint of CVD events, although there is certainly reason to believe it does,” he said in an interview, noting that he’s often used CACS to stratify atherosclerotic CVD risk in patients.
“I will now consider extending that assessment to patients with lower A1c levels,” he said.
If future studies validate this finding, he said, “serious consideration will have to be made for treating the very large numbers of patients with A1c levels in the prediabetic range and below with antidiabetic agents that have ASCVD prevention properties while lowering A1c. We have those agents today.”
The Progression of Early Subclinical Atherosclerosis study received funding from the National Center for Cardiovascular Investigation in Madrid, Santander Bank, and the Carlos III Health Institute in Madrid. Dr. Fuster had no disclosures. Dr. Ballantyne disclosed receiving research funding through his institution from Abbott Diagnostic, Akcea, Amgen, Esperion, Ionis, Novartis, Regeneron, and Roche Diagnostic; and has served as a consultant for Abbott Diagnostics, Althera, Amarin, Amgen, Arrowhead, AstraZeneca, Corvidia, Denka Seiken, Esperion, Genentech, Gilead, Matinas BioPharma, New Amsterdam, Novartis, Novo Nordisk, Pfizer, Regeneron, Roche Diagnostic and Sanofi-Synthélabo.
Dr. Jellinger had no disclosures.
, according to an analysis of data on almost 4,000 middle-aged individuals.
“If one looks at the incidence of generalized subclinical atherosclerosis, we are not talking small numbers,” senior study author Valentin Fuster, MD, PhD, said in an interview. “We are talking about between 45% and 82% of this middle-age population that already has atherosclerotic disease subclinically.
“Actually,” he added, “the disease was extensive in 5%-30% of these individuals of middle age.”
The study included 3,973 participants from the Progression of Early Subclinical Atherosclerosis study who did not have diabetes. A1c showed an association with the prevalence and multiterritorial extent of subclinical atherosclerosis as measured by two-dimensional ultrasound and coronary artery calcium score (CACS; P < .001). For example, those with A1c above 6.1% (133 participants) had a 33.1% rate of generalized subclinical atherosclerosis, compared with 4.9% for those with A1c below 4.8% (243), the lowest-score group in the study.
Patients in the subprediabetes band, between 5.0% and 5.5%, had significantly higher rates of generalized subclinical atherosclerosis than did the lowest-score group: 8% in the 4.9%-5.0% group (375 participants); 9.9% in the 5.1%-5.2% range (687); 10.3% in the 5.3%-5.4% group (928); and 11.5% in the 5.5%-5.6% group (842).
Those in the 5.1%-5.2% and 5/3%-5.4% A1c groups had a 27% greater chance of having subclinical atherosclerosis, while those in the 5.5%-5.6% group had a 36% greater risk, according to an odds ratio analysis adjusted for established cardiovascular risk factors. The risks were even higher for patients with prediabetes, the researchers reported in the Journal of the American College of Cardiology.
A call for earlier intervention
Notably, the study found that fasting plasma glucose testing did not yield a similar association between A1c and atherosclerosis.
“The message is that we all talk about people when they are close to the development of cardiovascular events, and here we are talking about people who we should pay attention to much earlier,” said Dr. Fuster, physician-in-chief at Icahn School of Medicine at Mount Sinai in New York and director of the National Center for Cardiovascular Investigation in Madrid, where the observational study originated said. “People should be sensitized to HbA1c much more than they would’ve been in the past, and I think this study actually validates that.”
Christie Ballantyne, MD, noted in an interview that these findings support the utility of A1c for predicting CVD risk.
“I think more and more we should be ordering a HbA1c” during routine physical exams, Dr. Ballantyne said. “You don’t have to be obese to get it; there are lots of people, maybe they’re slightly overweight. It’s a reasonable test to be getting when you get to middle age and older to get an idea for assessing for both developing diabetes and also the presence of atherosclerosis and the risk for having cardiovascular events.”
Dr. Ballantyne, chief of cardiology at Baylor College of Medicine and director of cardiovascular disease prevention at Methodist DeBakey Heart Center in Houston, coauthored an editorial comment on the study.
Clinicians typically start to manage CVD and diabetes risk “late in the process,” Dr. Ballantyne said. This study suggested that earlier use of antidiabetes therapies, namely peptide-1 agonists and semisynthetic glucagon-like peptide-2 inhibitors, may be warranted in patients with intermediate risk of CVD.
“It’s just more data for the rationale that, perhaps we could end up doing trials to show we can take high-risk people and prevent them from getting both heart disease and diabetes,” Dr. Ballantyne added. “Could we start a little earlier with better precision?”
These finding don’t yet call for a change in how cardiologists and endocrinologists manage patients on the cusp of prediabetes, said Paul S. Jellinger, MD, of Hollywood, Fla., and a professor at the University of Miami. “The endpoint of subclinical atherosclerosis does not necessarily translate into the harder endpoint of CVD events, although there is certainly reason to believe it does,” he said in an interview, noting that he’s often used CACS to stratify atherosclerotic CVD risk in patients.
“I will now consider extending that assessment to patients with lower A1c levels,” he said.
If future studies validate this finding, he said, “serious consideration will have to be made for treating the very large numbers of patients with A1c levels in the prediabetic range and below with antidiabetic agents that have ASCVD prevention properties while lowering A1c. We have those agents today.”
The Progression of Early Subclinical Atherosclerosis study received funding from the National Center for Cardiovascular Investigation in Madrid, Santander Bank, and the Carlos III Health Institute in Madrid. Dr. Fuster had no disclosures. Dr. Ballantyne disclosed receiving research funding through his institution from Abbott Diagnostic, Akcea, Amgen, Esperion, Ionis, Novartis, Regeneron, and Roche Diagnostic; and has served as a consultant for Abbott Diagnostics, Althera, Amarin, Amgen, Arrowhead, AstraZeneca, Corvidia, Denka Seiken, Esperion, Genentech, Gilead, Matinas BioPharma, New Amsterdam, Novartis, Novo Nordisk, Pfizer, Regeneron, Roche Diagnostic and Sanofi-Synthélabo.
Dr. Jellinger had no disclosures.
, according to an analysis of data on almost 4,000 middle-aged individuals.
“If one looks at the incidence of generalized subclinical atherosclerosis, we are not talking small numbers,” senior study author Valentin Fuster, MD, PhD, said in an interview. “We are talking about between 45% and 82% of this middle-age population that already has atherosclerotic disease subclinically.
“Actually,” he added, “the disease was extensive in 5%-30% of these individuals of middle age.”
The study included 3,973 participants from the Progression of Early Subclinical Atherosclerosis study who did not have diabetes. A1c showed an association with the prevalence and multiterritorial extent of subclinical atherosclerosis as measured by two-dimensional ultrasound and coronary artery calcium score (CACS; P < .001). For example, those with A1c above 6.1% (133 participants) had a 33.1% rate of generalized subclinical atherosclerosis, compared with 4.9% for those with A1c below 4.8% (243), the lowest-score group in the study.
Patients in the subprediabetes band, between 5.0% and 5.5%, had significantly higher rates of generalized subclinical atherosclerosis than did the lowest-score group: 8% in the 4.9%-5.0% group (375 participants); 9.9% in the 5.1%-5.2% range (687); 10.3% in the 5.3%-5.4% group (928); and 11.5% in the 5.5%-5.6% group (842).
Those in the 5.1%-5.2% and 5/3%-5.4% A1c groups had a 27% greater chance of having subclinical atherosclerosis, while those in the 5.5%-5.6% group had a 36% greater risk, according to an odds ratio analysis adjusted for established cardiovascular risk factors. The risks were even higher for patients with prediabetes, the researchers reported in the Journal of the American College of Cardiology.
A call for earlier intervention
Notably, the study found that fasting plasma glucose testing did not yield a similar association between A1c and atherosclerosis.
“The message is that we all talk about people when they are close to the development of cardiovascular events, and here we are talking about people who we should pay attention to much earlier,” said Dr. Fuster, physician-in-chief at Icahn School of Medicine at Mount Sinai in New York and director of the National Center for Cardiovascular Investigation in Madrid, where the observational study originated said. “People should be sensitized to HbA1c much more than they would’ve been in the past, and I think this study actually validates that.”
Christie Ballantyne, MD, noted in an interview that these findings support the utility of A1c for predicting CVD risk.
“I think more and more we should be ordering a HbA1c” during routine physical exams, Dr. Ballantyne said. “You don’t have to be obese to get it; there are lots of people, maybe they’re slightly overweight. It’s a reasonable test to be getting when you get to middle age and older to get an idea for assessing for both developing diabetes and also the presence of atherosclerosis and the risk for having cardiovascular events.”
Dr. Ballantyne, chief of cardiology at Baylor College of Medicine and director of cardiovascular disease prevention at Methodist DeBakey Heart Center in Houston, coauthored an editorial comment on the study.
Clinicians typically start to manage CVD and diabetes risk “late in the process,” Dr. Ballantyne said. This study suggested that earlier use of antidiabetes therapies, namely peptide-1 agonists and semisynthetic glucagon-like peptide-2 inhibitors, may be warranted in patients with intermediate risk of CVD.
“It’s just more data for the rationale that, perhaps we could end up doing trials to show we can take high-risk people and prevent them from getting both heart disease and diabetes,” Dr. Ballantyne added. “Could we start a little earlier with better precision?”
These finding don’t yet call for a change in how cardiologists and endocrinologists manage patients on the cusp of prediabetes, said Paul S. Jellinger, MD, of Hollywood, Fla., and a professor at the University of Miami. “The endpoint of subclinical atherosclerosis does not necessarily translate into the harder endpoint of CVD events, although there is certainly reason to believe it does,” he said in an interview, noting that he’s often used CACS to stratify atherosclerotic CVD risk in patients.
“I will now consider extending that assessment to patients with lower A1c levels,” he said.
If future studies validate this finding, he said, “serious consideration will have to be made for treating the very large numbers of patients with A1c levels in the prediabetic range and below with antidiabetic agents that have ASCVD prevention properties while lowering A1c. We have those agents today.”
The Progression of Early Subclinical Atherosclerosis study received funding from the National Center for Cardiovascular Investigation in Madrid, Santander Bank, and the Carlos III Health Institute in Madrid. Dr. Fuster had no disclosures. Dr. Ballantyne disclosed receiving research funding through his institution from Abbott Diagnostic, Akcea, Amgen, Esperion, Ionis, Novartis, Regeneron, and Roche Diagnostic; and has served as a consultant for Abbott Diagnostics, Althera, Amarin, Amgen, Arrowhead, AstraZeneca, Corvidia, Denka Seiken, Esperion, Genentech, Gilead, Matinas BioPharma, New Amsterdam, Novartis, Novo Nordisk, Pfizer, Regeneron, Roche Diagnostic and Sanofi-Synthélabo.
Dr. Jellinger had no disclosures.
FROM THE JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
Medtronic yanks Heartware VAD, calls for halt to new implants
Medtronic has stopped the sale of its Heartware Ventricular Assist Device (HVAD) system and is advising that physicians cease implanting the device because problems with an internal pump can lead to death or serious injuries.
“There is an increased risk of neurological adverse events and mortality associated with the internal pump,” the U.S. Food and Drug Administration announced today.
There is also a potential for the internal pump to stop, and there may be delay or failure to restart. “Both problems may lead to death or serious injuries,” the agency said.
Between January 2009 and April 22, 2021, Medtronic received a total of 106 complaints involving delay or failure to restart with the HVAD pump. Of these, 26 complaints involved HVAD devices operating under normal conditions (dual stator mode) and 80 involved devices operating in a back-up mode (single stator mode) that allows for continued pump function if electrical continuity between the pump and controller is interrupted.
Of the 26 complaints that occurred under normal conditions, four resulted in patient death and five led to urgent explant. Of the 80 complaints that occurred in single stator mode, 10 deaths and eight explants were reported to Medtronic, according to an urgent medical device communication letter issued by the company today.
“Considering these findings and given the availability of alternative devices such as the Abbott HeartMate 3, Medtronic has made the decision to stop the distribution and sale of the HVAD System,” the letter says. “Medtronic advises that there be no further implantations of the HVAD System.”
Medtronic undertook a previous recall of the Heartware HVAD system in February, focusing on batteries, power, datalink cables, and other peripheral equipment, because of the “risk of wear and tear of the connector plugs (power sources, data cable, and alarm adapter), which could cause damage to the controller port metal pins (for example, bent pins).” The FDA deemed that recall Class I, the most serious category of safety alert, in April.
The company noted that patients who currently have an HVAD implant “may require support for many years,” and that it is moving as quickly as possible to create a plan to guide the ongoing support for patients, caregivers, and health care professionals.
In response to the restart failure issue and evolving data about neurologic risks associated with the HVAD pump, Medtronic said it engaged an Independent Practitioner Quality Panel (IPQP), composed of cardiologists, surgeons, and VAD coordinators, to advise on recommendations for appropriate patient management. Based on information collected to date and IPQP input, Medtronic is recommending that physicians continue following best clinical practices and manage patients implanted with the HVAD pump according to the recommendations in the Instructions for Use (IFU).
“Prophylactic explant of the HVAD™ device is not recommended, as risks associated with explantation may outweigh the potential benefits,” the letter says. “The decision regarding explant and exchange of the HVAD™ pump should be made by physicians on a case-by-case basis, considering the patient’s clinical condition and surgical risks. If a physician determines that pump exchange is appropriate, we recommend exchanging to an alternative commercial LVAD.”
For patients in urgent need of an LVAD, Medtronic said physicians should use an alternative commercial LVAD or, if one is not available, that “a Patient Information form is required to be completed by you and your patient to acknowledge the risks of an HVAD implant prior to implanting your HVAD inventory.”
Today’s letter also provides recommendations on blood pressure management goals and anticoagulation. For any other questions or concerns, physicians should contact the Medtronic Office of Medical Affairs at: atrs.mcsmedicalaffairs@medtronic.com.
Medtronic issued another urgent letter in December 2020, warning physicians that a subset of HVAD devices included an internal pump component from three specific lots that increased the risk for restart failure. At that time, the company had not been able to pinpoint a root cause of the pump restart failure.
Consistent with the December 2020 notice, the rate of failure among pumps outside of the subset of three specific lots currently remains at about 0.4%, according to today’s notice.
Although Medtronic has identified the root cause and mitigations for pumps within the three specific lots, it has not been able to identify a root cause of the other restart failures reported with the HVAD pumps, the company said.
A version of this article first appeared on Medscape.com.
Medtronic has stopped the sale of its Heartware Ventricular Assist Device (HVAD) system and is advising that physicians cease implanting the device because problems with an internal pump can lead to death or serious injuries.
“There is an increased risk of neurological adverse events and mortality associated with the internal pump,” the U.S. Food and Drug Administration announced today.
There is also a potential for the internal pump to stop, and there may be delay or failure to restart. “Both problems may lead to death or serious injuries,” the agency said.
Between January 2009 and April 22, 2021, Medtronic received a total of 106 complaints involving delay or failure to restart with the HVAD pump. Of these, 26 complaints involved HVAD devices operating under normal conditions (dual stator mode) and 80 involved devices operating in a back-up mode (single stator mode) that allows for continued pump function if electrical continuity between the pump and controller is interrupted.
Of the 26 complaints that occurred under normal conditions, four resulted in patient death and five led to urgent explant. Of the 80 complaints that occurred in single stator mode, 10 deaths and eight explants were reported to Medtronic, according to an urgent medical device communication letter issued by the company today.
“Considering these findings and given the availability of alternative devices such as the Abbott HeartMate 3, Medtronic has made the decision to stop the distribution and sale of the HVAD System,” the letter says. “Medtronic advises that there be no further implantations of the HVAD System.”
Medtronic undertook a previous recall of the Heartware HVAD system in February, focusing on batteries, power, datalink cables, and other peripheral equipment, because of the “risk of wear and tear of the connector plugs (power sources, data cable, and alarm adapter), which could cause damage to the controller port metal pins (for example, bent pins).” The FDA deemed that recall Class I, the most serious category of safety alert, in April.
The company noted that patients who currently have an HVAD implant “may require support for many years,” and that it is moving as quickly as possible to create a plan to guide the ongoing support for patients, caregivers, and health care professionals.
In response to the restart failure issue and evolving data about neurologic risks associated with the HVAD pump, Medtronic said it engaged an Independent Practitioner Quality Panel (IPQP), composed of cardiologists, surgeons, and VAD coordinators, to advise on recommendations for appropriate patient management. Based on information collected to date and IPQP input, Medtronic is recommending that physicians continue following best clinical practices and manage patients implanted with the HVAD pump according to the recommendations in the Instructions for Use (IFU).
“Prophylactic explant of the HVAD™ device is not recommended, as risks associated with explantation may outweigh the potential benefits,” the letter says. “The decision regarding explant and exchange of the HVAD™ pump should be made by physicians on a case-by-case basis, considering the patient’s clinical condition and surgical risks. If a physician determines that pump exchange is appropriate, we recommend exchanging to an alternative commercial LVAD.”
For patients in urgent need of an LVAD, Medtronic said physicians should use an alternative commercial LVAD or, if one is not available, that “a Patient Information form is required to be completed by you and your patient to acknowledge the risks of an HVAD implant prior to implanting your HVAD inventory.”
Today’s letter also provides recommendations on blood pressure management goals and anticoagulation. For any other questions or concerns, physicians should contact the Medtronic Office of Medical Affairs at: atrs.mcsmedicalaffairs@medtronic.com.
Medtronic issued another urgent letter in December 2020, warning physicians that a subset of HVAD devices included an internal pump component from three specific lots that increased the risk for restart failure. At that time, the company had not been able to pinpoint a root cause of the pump restart failure.
Consistent with the December 2020 notice, the rate of failure among pumps outside of the subset of three specific lots currently remains at about 0.4%, according to today’s notice.
Although Medtronic has identified the root cause and mitigations for pumps within the three specific lots, it has not been able to identify a root cause of the other restart failures reported with the HVAD pumps, the company said.
A version of this article first appeared on Medscape.com.
Medtronic has stopped the sale of its Heartware Ventricular Assist Device (HVAD) system and is advising that physicians cease implanting the device because problems with an internal pump can lead to death or serious injuries.
“There is an increased risk of neurological adverse events and mortality associated with the internal pump,” the U.S. Food and Drug Administration announced today.
There is also a potential for the internal pump to stop, and there may be delay or failure to restart. “Both problems may lead to death or serious injuries,” the agency said.
Between January 2009 and April 22, 2021, Medtronic received a total of 106 complaints involving delay or failure to restart with the HVAD pump. Of these, 26 complaints involved HVAD devices operating under normal conditions (dual stator mode) and 80 involved devices operating in a back-up mode (single stator mode) that allows for continued pump function if electrical continuity between the pump and controller is interrupted.
Of the 26 complaints that occurred under normal conditions, four resulted in patient death and five led to urgent explant. Of the 80 complaints that occurred in single stator mode, 10 deaths and eight explants were reported to Medtronic, according to an urgent medical device communication letter issued by the company today.
“Considering these findings and given the availability of alternative devices such as the Abbott HeartMate 3, Medtronic has made the decision to stop the distribution and sale of the HVAD System,” the letter says. “Medtronic advises that there be no further implantations of the HVAD System.”
Medtronic undertook a previous recall of the Heartware HVAD system in February, focusing on batteries, power, datalink cables, and other peripheral equipment, because of the “risk of wear and tear of the connector plugs (power sources, data cable, and alarm adapter), which could cause damage to the controller port metal pins (for example, bent pins).” The FDA deemed that recall Class I, the most serious category of safety alert, in April.
The company noted that patients who currently have an HVAD implant “may require support for many years,” and that it is moving as quickly as possible to create a plan to guide the ongoing support for patients, caregivers, and health care professionals.
In response to the restart failure issue and evolving data about neurologic risks associated with the HVAD pump, Medtronic said it engaged an Independent Practitioner Quality Panel (IPQP), composed of cardiologists, surgeons, and VAD coordinators, to advise on recommendations for appropriate patient management. Based on information collected to date and IPQP input, Medtronic is recommending that physicians continue following best clinical practices and manage patients implanted with the HVAD pump according to the recommendations in the Instructions for Use (IFU).
“Prophylactic explant of the HVAD™ device is not recommended, as risks associated with explantation may outweigh the potential benefits,” the letter says. “The decision regarding explant and exchange of the HVAD™ pump should be made by physicians on a case-by-case basis, considering the patient’s clinical condition and surgical risks. If a physician determines that pump exchange is appropriate, we recommend exchanging to an alternative commercial LVAD.”
For patients in urgent need of an LVAD, Medtronic said physicians should use an alternative commercial LVAD or, if one is not available, that “a Patient Information form is required to be completed by you and your patient to acknowledge the risks of an HVAD implant prior to implanting your HVAD inventory.”
Today’s letter also provides recommendations on blood pressure management goals and anticoagulation. For any other questions or concerns, physicians should contact the Medtronic Office of Medical Affairs at: atrs.mcsmedicalaffairs@medtronic.com.
Medtronic issued another urgent letter in December 2020, warning physicians that a subset of HVAD devices included an internal pump component from three specific lots that increased the risk for restart failure. At that time, the company had not been able to pinpoint a root cause of the pump restart failure.
Consistent with the December 2020 notice, the rate of failure among pumps outside of the subset of three specific lots currently remains at about 0.4%, according to today’s notice.
Although Medtronic has identified the root cause and mitigations for pumps within the three specific lots, it has not been able to identify a root cause of the other restart failures reported with the HVAD pumps, the company said.
A version of this article first appeared on Medscape.com.
NCAA athletes: ECG abnormalities persist after COVID-19
College athletes who have recently recovered from COVID-19 infection show cardiac abnormalities on electrocardiography.
In a small study of ECGs on National Collegiate Athletic Association Division II athletes, those who had been infected with COVID-19 had a prolonged PR interval, compared with matched athletes who had not been infected.
The study was presented at the 2021 Virtual American College of Sports Medicine Annual Meeting & World Congresses.
“The NCAA was requiring athletes to have an ECG for return to play after noting there could be some myocardial abnormalities following COVID-19 infection,” lead author Frank Wyatt, EdD, a sports physiologist and professor at Midwestern State University in Wichita Falls, Tex., told this news organization.
“Our head athletic trainer asked me if I could do ECGs on our COVID-19–recovered athletes, and I decided to do a matched pair–design study to see how our infected and noninfected athletes compared,” Dr. Wyatt said.
Research in the general population has suggested that COVID-19 can cause damage not only to the lungs, but also to the myocardium, he said. “Recent literature suggests COVID-19 is actually infusing itself into the cells of the myocardium and killing those cells, much the way it did in the lung, and possibly kidney and liver, so it’s going after those organs as well, not just the lungs.”
Dr. Wyatt presented results of ECGs that were done in seven COVID-infected athletes and in seven controls, who were free of infection.
The athletes’ recovery from COVID-19 infection was documented after two negative tests.
All subjects were matched by sport, gender, ethnicity, and anthropometry. Investigators obtained ECG recordings 2-4 weeks after the infected athletes had their recovery documented.
Study participants engaged in football, basketball, soccer, and volleyball, and Dr. Wyatt and associates were blinded as to their infected or control status.
Participants self-reported their ethnicity. Most were White or African American.
The main abnormality found was a prolonged PR interval. In the athletes who were recovered from COVID-19, the mean PR interval was 183.6 milliseconds (± 32.4 ms), compared with 141.7 ms (± 22.7 ms) among the controls.
Baseline ECGs for all young athletes?
Dr. Wyatt said he would like to see ECGs done at baseline as part of the physical exam NCAA athletes have to undergo at the start of each season. But that would be expensive.
“It has been suggested that they all need to have ECGs for baseline information, but they don’t do it because of money. If we had that baseline data on these athletes it would really give us a better picture of whether there was damage or not,” he said. “At our small university, if I wasn’t available to do these ECGs, our athletic department would then have to go to the cardiologist to do them, and that is tremendously expensive. It has also been suggested that high school athletes get ECGs as a preliminary test when they start their season, and I think that is warranted as well as for the NCAA athletes, but because of the expense, they’re not doing it.”
Dr. Wyatt has continued to do ECGs on athletes who have survived COVID-19 and to date has ECG data on 70 athletes. He plans further comparisons between the infected and noninfected athletes.
“We want to see if we can solidify the results we presented at ACSM. We had small numbers, so our follow up is to see if we can statistically show in a more robust manner whether or not there was widespread abnormality in the athletes who got infected. They were only 2-4 weeks post infected, and I don’t know what the long-term effects are going to be,” he said.
May be an important finding
“This may be an important finding, but needs many more athletes, as there were only seven in each group,” commented Curt J. Daniels, MD, director of the sports cardiology program and professor at Ohio State University Wexner Medical Center, Columbus.
“Plus, it will need some imaging correlate and recovery ECGs to see if this effect of PR interval prolongation correlates with myocardial changes and whether it persists or resolves,” added Dr. Daniels, who was not part of the study. “But I do find this interesting. ... I agree we are looking for any ECG sign that might help tell us who needs a cardiac MRI. The Big Ten COVID-19 Cardiac Registry has 1,597 ECGs on post COVID athletes we are analyzing, but preliminarily did not see any changes.”
Dr. Wyatt and Dr. Daniels reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
College athletes who have recently recovered from COVID-19 infection show cardiac abnormalities on electrocardiography.
In a small study of ECGs on National Collegiate Athletic Association Division II athletes, those who had been infected with COVID-19 had a prolonged PR interval, compared with matched athletes who had not been infected.
The study was presented at the 2021 Virtual American College of Sports Medicine Annual Meeting & World Congresses.
“The NCAA was requiring athletes to have an ECG for return to play after noting there could be some myocardial abnormalities following COVID-19 infection,” lead author Frank Wyatt, EdD, a sports physiologist and professor at Midwestern State University in Wichita Falls, Tex., told this news organization.
“Our head athletic trainer asked me if I could do ECGs on our COVID-19–recovered athletes, and I decided to do a matched pair–design study to see how our infected and noninfected athletes compared,” Dr. Wyatt said.
Research in the general population has suggested that COVID-19 can cause damage not only to the lungs, but also to the myocardium, he said. “Recent literature suggests COVID-19 is actually infusing itself into the cells of the myocardium and killing those cells, much the way it did in the lung, and possibly kidney and liver, so it’s going after those organs as well, not just the lungs.”
Dr. Wyatt presented results of ECGs that were done in seven COVID-infected athletes and in seven controls, who were free of infection.
The athletes’ recovery from COVID-19 infection was documented after two negative tests.
All subjects were matched by sport, gender, ethnicity, and anthropometry. Investigators obtained ECG recordings 2-4 weeks after the infected athletes had their recovery documented.
Study participants engaged in football, basketball, soccer, and volleyball, and Dr. Wyatt and associates were blinded as to their infected or control status.
Participants self-reported their ethnicity. Most were White or African American.
The main abnormality found was a prolonged PR interval. In the athletes who were recovered from COVID-19, the mean PR interval was 183.6 milliseconds (± 32.4 ms), compared with 141.7 ms (± 22.7 ms) among the controls.
Baseline ECGs for all young athletes?
Dr. Wyatt said he would like to see ECGs done at baseline as part of the physical exam NCAA athletes have to undergo at the start of each season. But that would be expensive.
“It has been suggested that they all need to have ECGs for baseline information, but they don’t do it because of money. If we had that baseline data on these athletes it would really give us a better picture of whether there was damage or not,” he said. “At our small university, if I wasn’t available to do these ECGs, our athletic department would then have to go to the cardiologist to do them, and that is tremendously expensive. It has also been suggested that high school athletes get ECGs as a preliminary test when they start their season, and I think that is warranted as well as for the NCAA athletes, but because of the expense, they’re not doing it.”
Dr. Wyatt has continued to do ECGs on athletes who have survived COVID-19 and to date has ECG data on 70 athletes. He plans further comparisons between the infected and noninfected athletes.
“We want to see if we can solidify the results we presented at ACSM. We had small numbers, so our follow up is to see if we can statistically show in a more robust manner whether or not there was widespread abnormality in the athletes who got infected. They were only 2-4 weeks post infected, and I don’t know what the long-term effects are going to be,” he said.
May be an important finding
“This may be an important finding, but needs many more athletes, as there were only seven in each group,” commented Curt J. Daniels, MD, director of the sports cardiology program and professor at Ohio State University Wexner Medical Center, Columbus.
“Plus, it will need some imaging correlate and recovery ECGs to see if this effect of PR interval prolongation correlates with myocardial changes and whether it persists or resolves,” added Dr. Daniels, who was not part of the study. “But I do find this interesting. ... I agree we are looking for any ECG sign that might help tell us who needs a cardiac MRI. The Big Ten COVID-19 Cardiac Registry has 1,597 ECGs on post COVID athletes we are analyzing, but preliminarily did not see any changes.”
Dr. Wyatt and Dr. Daniels reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
College athletes who have recently recovered from COVID-19 infection show cardiac abnormalities on electrocardiography.
In a small study of ECGs on National Collegiate Athletic Association Division II athletes, those who had been infected with COVID-19 had a prolonged PR interval, compared with matched athletes who had not been infected.
The study was presented at the 2021 Virtual American College of Sports Medicine Annual Meeting & World Congresses.
“The NCAA was requiring athletes to have an ECG for return to play after noting there could be some myocardial abnormalities following COVID-19 infection,” lead author Frank Wyatt, EdD, a sports physiologist and professor at Midwestern State University in Wichita Falls, Tex., told this news organization.
“Our head athletic trainer asked me if I could do ECGs on our COVID-19–recovered athletes, and I decided to do a matched pair–design study to see how our infected and noninfected athletes compared,” Dr. Wyatt said.
Research in the general population has suggested that COVID-19 can cause damage not only to the lungs, but also to the myocardium, he said. “Recent literature suggests COVID-19 is actually infusing itself into the cells of the myocardium and killing those cells, much the way it did in the lung, and possibly kidney and liver, so it’s going after those organs as well, not just the lungs.”
Dr. Wyatt presented results of ECGs that were done in seven COVID-infected athletes and in seven controls, who were free of infection.
The athletes’ recovery from COVID-19 infection was documented after two negative tests.
All subjects were matched by sport, gender, ethnicity, and anthropometry. Investigators obtained ECG recordings 2-4 weeks after the infected athletes had their recovery documented.
Study participants engaged in football, basketball, soccer, and volleyball, and Dr. Wyatt and associates were blinded as to their infected or control status.
Participants self-reported their ethnicity. Most were White or African American.
The main abnormality found was a prolonged PR interval. In the athletes who were recovered from COVID-19, the mean PR interval was 183.6 milliseconds (± 32.4 ms), compared with 141.7 ms (± 22.7 ms) among the controls.
Baseline ECGs for all young athletes?
Dr. Wyatt said he would like to see ECGs done at baseline as part of the physical exam NCAA athletes have to undergo at the start of each season. But that would be expensive.
“It has been suggested that they all need to have ECGs for baseline information, but they don’t do it because of money. If we had that baseline data on these athletes it would really give us a better picture of whether there was damage or not,” he said. “At our small university, if I wasn’t available to do these ECGs, our athletic department would then have to go to the cardiologist to do them, and that is tremendously expensive. It has also been suggested that high school athletes get ECGs as a preliminary test when they start their season, and I think that is warranted as well as for the NCAA athletes, but because of the expense, they’re not doing it.”
Dr. Wyatt has continued to do ECGs on athletes who have survived COVID-19 and to date has ECG data on 70 athletes. He plans further comparisons between the infected and noninfected athletes.
“We want to see if we can solidify the results we presented at ACSM. We had small numbers, so our follow up is to see if we can statistically show in a more robust manner whether or not there was widespread abnormality in the athletes who got infected. They were only 2-4 weeks post infected, and I don’t know what the long-term effects are going to be,” he said.
May be an important finding
“This may be an important finding, but needs many more athletes, as there were only seven in each group,” commented Curt J. Daniels, MD, director of the sports cardiology program and professor at Ohio State University Wexner Medical Center, Columbus.
“Plus, it will need some imaging correlate and recovery ECGs to see if this effect of PR interval prolongation correlates with myocardial changes and whether it persists or resolves,” added Dr. Daniels, who was not part of the study. “But I do find this interesting. ... I agree we are looking for any ECG sign that might help tell us who needs a cardiac MRI. The Big Ten COVID-19 Cardiac Registry has 1,597 ECGs on post COVID athletes we are analyzing, but preliminarily did not see any changes.”
Dr. Wyatt and Dr. Daniels reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Intersection of trauma and race in pregnancy calls for more study
Black patients experienced more moderate to severe violent trauma during pregnancy than did non-Black patients at a single Baltimore institution, according to a small retrospective cohort study presented in a poster at the 2021 virtual meeting of the American College of Obstetricians and Gynecologists.
“Trauma is the leading nonobstetric cause of death in pregnant women,” and Black communities are at a disproportionately greater risk of trauma, Rebecca H. Jessel, MD, of Icahn School of Medicine at Mount Sinai in New York, and associates wrote in their poster.
The study’s findings raise research questions that need more exploration, according to Neel Shah, MD, assistant professor of obstetrics, gynecology, and reproductive biology at Harvard Medical School, Boston, and founding director of the Delivery Decisions Initiative at Harvard’s Ariadne Labs.
“This is an interesting study that opens a line of inquiry into how trauma may impact the pregnancies of those who are Black differently,” Dr. Shah, who was not involved in the research, said in an interview. “The observed disparity is consistent with the racial inequities in outcomes we see across obstetric outcomes and requires further research into the causes and solutions.”
The researchers retrospectively reviewed all pregnant patients treated between 2015 and 2018 at the University of Maryland’s R Adams Cowley Shock Trauma Center in Baltimore. In addition to maternal demographics, details about the delivery, and perinatal outcomes, the researchers noted whether the trauma was violent, such as assault, or nonviolent, such as motor vehicle accidents. Moderate to severe trauma was defined as an injury severity score of at least 9.
Among 3,536 women aged 15-49 treated at the shock trauma center, 62 were pregnant, and 71% of these women were Black. Nineteen percent were White patients, 5% were Asian patients, and 5% were of a different race/ethnicity. Black patients were, on average, 27 years old at the time of the trauma. Non-Black patients were, on average, 25 years old. The average gestational age at the time of trauma was 25 weeks, 3 days in Black women and 23 weeks, 4 days in non-Black women.
The most common cause of trauma was a car accident, implicated in 56% of the trauma cases. Assault was the next most common cause of trauma, making up nearly a quarter (23%) of cases. The other injuries came from accidents (16%) or inhalation (5%). The average injury severity score was 4.7, with a mild injury for 76% of patients and a moderate to severe injury in 24%.
The researchers then compared the mechanisms and severity of injuries between Black and non-Black patients. The severity of trauma was similar between the two groups: Seventy-five percent of Black patients and 78% of non-Black patients had mild trauma with injury severity scores below 9. However, assault or another violent form of trauma was more likely to occur to Black patients than to non-Black patients. More than a quarter (27%) of Black patients experienced violent trauma, compared to 11% of non-Black patients.
“It is very notable that among pregnant people who experience trauma, obstetric complications leading to preterm delivery were observed much more often for those who are Black,” Dr. Shah said. “A case series to understand the underlying causes could be very valuable.”
Black patients delivered an average 59 days (8 weeks, 3 days) after the trauma compared to an average 83 days (11 weeks, 6 days) for non-Black patients, but the difference was not statistically significant. However, preterm birth was more likely in non-Black patients (83%) than in Black patients (78%). A similar proportion of deliveries were preterm in Black (57%) and non-Black (56%) patients.
Though the poster did not show the data, the researchers wrote that Black women who experienced moderate to severe trauma after 24 weeks’ gestational age either had a preterm birth or a fetal demise.
Though the study findings warrant deeper investigation, the study has substantial limitations.
“It is challenging to generalize from this study because the sample size is small and it is from a single institution,” Dr. Shah said. “It does not appear to be adequately powered to draw statistically significant conclusions. In particular, the data are not adequate to support the authors’ statement that Black people are more likely to experience the forms of described trauma generally.”
The authors and Dr. Shah reported no disclosures.
Black patients experienced more moderate to severe violent trauma during pregnancy than did non-Black patients at a single Baltimore institution, according to a small retrospective cohort study presented in a poster at the 2021 virtual meeting of the American College of Obstetricians and Gynecologists.
“Trauma is the leading nonobstetric cause of death in pregnant women,” and Black communities are at a disproportionately greater risk of trauma, Rebecca H. Jessel, MD, of Icahn School of Medicine at Mount Sinai in New York, and associates wrote in their poster.
The study’s findings raise research questions that need more exploration, according to Neel Shah, MD, assistant professor of obstetrics, gynecology, and reproductive biology at Harvard Medical School, Boston, and founding director of the Delivery Decisions Initiative at Harvard’s Ariadne Labs.
“This is an interesting study that opens a line of inquiry into how trauma may impact the pregnancies of those who are Black differently,” Dr. Shah, who was not involved in the research, said in an interview. “The observed disparity is consistent with the racial inequities in outcomes we see across obstetric outcomes and requires further research into the causes and solutions.”
The researchers retrospectively reviewed all pregnant patients treated between 2015 and 2018 at the University of Maryland’s R Adams Cowley Shock Trauma Center in Baltimore. In addition to maternal demographics, details about the delivery, and perinatal outcomes, the researchers noted whether the trauma was violent, such as assault, or nonviolent, such as motor vehicle accidents. Moderate to severe trauma was defined as an injury severity score of at least 9.
Among 3,536 women aged 15-49 treated at the shock trauma center, 62 were pregnant, and 71% of these women were Black. Nineteen percent were White patients, 5% were Asian patients, and 5% were of a different race/ethnicity. Black patients were, on average, 27 years old at the time of the trauma. Non-Black patients were, on average, 25 years old. The average gestational age at the time of trauma was 25 weeks, 3 days in Black women and 23 weeks, 4 days in non-Black women.
The most common cause of trauma was a car accident, implicated in 56% of the trauma cases. Assault was the next most common cause of trauma, making up nearly a quarter (23%) of cases. The other injuries came from accidents (16%) or inhalation (5%). The average injury severity score was 4.7, with a mild injury for 76% of patients and a moderate to severe injury in 24%.
The researchers then compared the mechanisms and severity of injuries between Black and non-Black patients. The severity of trauma was similar between the two groups: Seventy-five percent of Black patients and 78% of non-Black patients had mild trauma with injury severity scores below 9. However, assault or another violent form of trauma was more likely to occur to Black patients than to non-Black patients. More than a quarter (27%) of Black patients experienced violent trauma, compared to 11% of non-Black patients.
“It is very notable that among pregnant people who experience trauma, obstetric complications leading to preterm delivery were observed much more often for those who are Black,” Dr. Shah said. “A case series to understand the underlying causes could be very valuable.”
Black patients delivered an average 59 days (8 weeks, 3 days) after the trauma compared to an average 83 days (11 weeks, 6 days) for non-Black patients, but the difference was not statistically significant. However, preterm birth was more likely in non-Black patients (83%) than in Black patients (78%). A similar proportion of deliveries were preterm in Black (57%) and non-Black (56%) patients.
Though the poster did not show the data, the researchers wrote that Black women who experienced moderate to severe trauma after 24 weeks’ gestational age either had a preterm birth or a fetal demise.
Though the study findings warrant deeper investigation, the study has substantial limitations.
“It is challenging to generalize from this study because the sample size is small and it is from a single institution,” Dr. Shah said. “It does not appear to be adequately powered to draw statistically significant conclusions. In particular, the data are not adequate to support the authors’ statement that Black people are more likely to experience the forms of described trauma generally.”
The authors and Dr. Shah reported no disclosures.
Black patients experienced more moderate to severe violent trauma during pregnancy than did non-Black patients at a single Baltimore institution, according to a small retrospective cohort study presented in a poster at the 2021 virtual meeting of the American College of Obstetricians and Gynecologists.
“Trauma is the leading nonobstetric cause of death in pregnant women,” and Black communities are at a disproportionately greater risk of trauma, Rebecca H. Jessel, MD, of Icahn School of Medicine at Mount Sinai in New York, and associates wrote in their poster.
The study’s findings raise research questions that need more exploration, according to Neel Shah, MD, assistant professor of obstetrics, gynecology, and reproductive biology at Harvard Medical School, Boston, and founding director of the Delivery Decisions Initiative at Harvard’s Ariadne Labs.
“This is an interesting study that opens a line of inquiry into how trauma may impact the pregnancies of those who are Black differently,” Dr. Shah, who was not involved in the research, said in an interview. “The observed disparity is consistent with the racial inequities in outcomes we see across obstetric outcomes and requires further research into the causes and solutions.”
The researchers retrospectively reviewed all pregnant patients treated between 2015 and 2018 at the University of Maryland’s R Adams Cowley Shock Trauma Center in Baltimore. In addition to maternal demographics, details about the delivery, and perinatal outcomes, the researchers noted whether the trauma was violent, such as assault, or nonviolent, such as motor vehicle accidents. Moderate to severe trauma was defined as an injury severity score of at least 9.
Among 3,536 women aged 15-49 treated at the shock trauma center, 62 were pregnant, and 71% of these women were Black. Nineteen percent were White patients, 5% were Asian patients, and 5% were of a different race/ethnicity. Black patients were, on average, 27 years old at the time of the trauma. Non-Black patients were, on average, 25 years old. The average gestational age at the time of trauma was 25 weeks, 3 days in Black women and 23 weeks, 4 days in non-Black women.
The most common cause of trauma was a car accident, implicated in 56% of the trauma cases. Assault was the next most common cause of trauma, making up nearly a quarter (23%) of cases. The other injuries came from accidents (16%) or inhalation (5%). The average injury severity score was 4.7, with a mild injury for 76% of patients and a moderate to severe injury in 24%.
The researchers then compared the mechanisms and severity of injuries between Black and non-Black patients. The severity of trauma was similar between the two groups: Seventy-five percent of Black patients and 78% of non-Black patients had mild trauma with injury severity scores below 9. However, assault or another violent form of trauma was more likely to occur to Black patients than to non-Black patients. More than a quarter (27%) of Black patients experienced violent trauma, compared to 11% of non-Black patients.
“It is very notable that among pregnant people who experience trauma, obstetric complications leading to preterm delivery were observed much more often for those who are Black,” Dr. Shah said. “A case series to understand the underlying causes could be very valuable.”
Black patients delivered an average 59 days (8 weeks, 3 days) after the trauma compared to an average 83 days (11 weeks, 6 days) for non-Black patients, but the difference was not statistically significant. However, preterm birth was more likely in non-Black patients (83%) than in Black patients (78%). A similar proportion of deliveries were preterm in Black (57%) and non-Black (56%) patients.
Though the poster did not show the data, the researchers wrote that Black women who experienced moderate to severe trauma after 24 weeks’ gestational age either had a preterm birth or a fetal demise.
Though the study findings warrant deeper investigation, the study has substantial limitations.
“It is challenging to generalize from this study because the sample size is small and it is from a single institution,” Dr. Shah said. “It does not appear to be adequately powered to draw statistically significant conclusions. In particular, the data are not adequate to support the authors’ statement that Black people are more likely to experience the forms of described trauma generally.”
The authors and Dr. Shah reported no disclosures.
FROM ACOG 2021
BEAT-LUPUS: Belimumab after rituximab delays severe flares
Using belimumab after rituximab to treat patients with systemic lupus erythematosus (SLE) refractory to conventional therapy not only significantly decreased levels of serum IgG anti-dsDNA antibody levels but also prolonged the time before severe flares of disease occurred in the phase 2b BEAT-LUPUS (Belimumab after B cell depletion in SLE) study.
The trial’s primary outcome of serum IgG anti-dsDNA antibody levels showed a decline from a geometric mean of 162 IU/mL at baseline to 69 IU/mL at 24 weeks and 47 IU/mL at 1 year in patients treated with belimumab (Benlysta) after rituximab (Rituxan and biosimilars). These reductions were significantly lower than the values seen in the placebo after rituximab arm (a respective 121 IU/mL, 99 IU/mL, and 103 IU/mL; P < .001).
Just 3 patients who received belimumab versus 10 who received placebo after rituximab experienced a severe BILAG (British Isles Lupus Assessment Group) index A flare by the end of the study at 52 weeks. The hazard ratio (HR) for the flare reduction was 0.27 (P = .03), indicating a 73% reduction.
The use of belimumab rather than a placebo also led to a small reduction in total serum IgG, and significantly suppressed B-cell repopulation (P = .03).
These results need confirming in a larger, phase 3 trial, the trial’s principal investigator, Michael Ehrenstein, PhD, said at the annual European Congress of Rheumatology. They are “clearly encouraging” and “support the hypothesis that BAFF [B-cell–activating factor] can drive flares after rituximab,” he said.
Although B-cell depletion with rituximab is recommended by national and international guidelines to treat some patients with SLE who are refractory to conventional therapy, its use is not licensed.
“Certainly, rituximab is a controversial drug in lupus,” Dr. Ehrenstein, a consultant rheumatologist based at University College London, said in an interview. Although there is real-world evidence from registries and open-label studies suggesting that it is widely used and effective in some patients, the randomized, controlled trials conducted with rituximab about 10 years ago failed to meet their primary endpoints.
“A lot has been written about why that was, but probably the biggest reason was the high dose of steroids in both groups,” Dr. Ehrenstein said. To try to avoid muddying the waters of the BEAT-LUPUS trial findings, the maximum dose of prednisolone allowed to be used as background therapy was 20 mg/day. The trial’s investigators were also encouraged to reduce the baseline steroid dose to at least 50% by the trial’s 6-month halfway point.
“We tried to reflect what was going on in the U.K.,” Dr. Ehrenstein said, noting that the inspiration for the trial was a patient who had received sequential rituximab treatment. Although she got better with each cycle of rituximab, when her disease flared it would be worse than the time before, with increasingly higher anti-dsDNA levels recorded. The reason for this seemed to be because of increasing BAFF levels, and so the hypothesis was that if rituximab was associated with increased BAFF levels, then co-targeting BAFF with belimumab should be able to prevent those flares from happening.
The BEAT-LUPUS trial has been a huge collaborative effort and was conducted across 16 U.K. centers. From initial funding to the data analysis, it has taken 6 years to complete and was made possible by a unique partnership between Versus Arthritis, University College London Hospitals Biomedical Research Center, the National Institute for Health Research UK Musculoskeletal Translational Research Collaboration, and GlaxoSmithKline (GSK). GSK provided belimumab free of charge, as well as additional funding, but had no role in the design of the study and will not have any role going forward.
From an initial 172 patients assessed for eligibility, 52 patients were finally enrolled into the trial and received rituximab as two infusions given 2 weeks apart. Patients were then randomized in a double-blind manner to receive either belimumab (n = 26) or placebo (n = 26) 4-8 weeks after their first dose of rituximab. The intention-to-treat population consisted of 43 patients.
The use of belimumab after rituximab did not increase the risk for infection – serious or otherwise – or adverse effects, Dr. Ehrenstein reported. Serious adverse events were reported in six (23%) patients in each arm, and serious infections were seen in two (8%) of the belimumab- and four (15%) of the placebo-treated patients.
“I think the take-home message is that it seems that belimumab can reduce the number of severe flares that occur after rituximab therapy,” Dr. Ehrenstein said. “It’s promising, but not definitive,” he added. The next step is of course to publish these data and to perform a phase 3 trial.
In the discussion time following the presentation, session moderator Xavier Mariette, MD, PhD, of Bicêtre Hospital, Paris-Saclay University, asked why not give belimumab first before rituximab if using belimumab afterward works?
“Our strategy was driven by the observation that BAFF levels surged after rituximab, and therefore it’s logical to give the belimumab to block that BAFF surge,” he answered.
“Certainly, there are ideas that belimumab releases mature B cells into the circulation and rituximab can target that,” he added. That strategy is under investigation in the BLISS-BELIEVE trial, which should also report by the end of this year. It’s a much larger, phase 3 trial, involving nearly 300 patients and is sponsored by GSK.
“Clearly, this is a combination treatment [but] whether you give one before the other is uncertain,” Dr. Ehrenstein observed.
Another member of the viewing audience asked whether it would have been a fairer comparison if another dose of rituximab had been given to patients at week 24 instead of no treatment. Dr. Ehrenstein noted that it was a “good point” to make, but the investigators mainly wanted to answer whether giving belimumab after rituximab would target BAFF and thereby drop serum anti-dsDNA antibody levels. He said that a full trial of rituximab for patients with SLE, perhaps adding this extra dose, needs to be conducted.
Dr. Ehrenstein disclosed receiving research funding and educational grants from GSK and participating in advisory panels for the company.
Using belimumab after rituximab to treat patients with systemic lupus erythematosus (SLE) refractory to conventional therapy not only significantly decreased levels of serum IgG anti-dsDNA antibody levels but also prolonged the time before severe flares of disease occurred in the phase 2b BEAT-LUPUS (Belimumab after B cell depletion in SLE) study.
The trial’s primary outcome of serum IgG anti-dsDNA antibody levels showed a decline from a geometric mean of 162 IU/mL at baseline to 69 IU/mL at 24 weeks and 47 IU/mL at 1 year in patients treated with belimumab (Benlysta) after rituximab (Rituxan and biosimilars). These reductions were significantly lower than the values seen in the placebo after rituximab arm (a respective 121 IU/mL, 99 IU/mL, and 103 IU/mL; P < .001).
Just 3 patients who received belimumab versus 10 who received placebo after rituximab experienced a severe BILAG (British Isles Lupus Assessment Group) index A flare by the end of the study at 52 weeks. The hazard ratio (HR) for the flare reduction was 0.27 (P = .03), indicating a 73% reduction.
The use of belimumab rather than a placebo also led to a small reduction in total serum IgG, and significantly suppressed B-cell repopulation (P = .03).
These results need confirming in a larger, phase 3 trial, the trial’s principal investigator, Michael Ehrenstein, PhD, said at the annual European Congress of Rheumatology. They are “clearly encouraging” and “support the hypothesis that BAFF [B-cell–activating factor] can drive flares after rituximab,” he said.
Although B-cell depletion with rituximab is recommended by national and international guidelines to treat some patients with SLE who are refractory to conventional therapy, its use is not licensed.
“Certainly, rituximab is a controversial drug in lupus,” Dr. Ehrenstein, a consultant rheumatologist based at University College London, said in an interview. Although there is real-world evidence from registries and open-label studies suggesting that it is widely used and effective in some patients, the randomized, controlled trials conducted with rituximab about 10 years ago failed to meet their primary endpoints.
“A lot has been written about why that was, but probably the biggest reason was the high dose of steroids in both groups,” Dr. Ehrenstein said. To try to avoid muddying the waters of the BEAT-LUPUS trial findings, the maximum dose of prednisolone allowed to be used as background therapy was 20 mg/day. The trial’s investigators were also encouraged to reduce the baseline steroid dose to at least 50% by the trial’s 6-month halfway point.
“We tried to reflect what was going on in the U.K.,” Dr. Ehrenstein said, noting that the inspiration for the trial was a patient who had received sequential rituximab treatment. Although she got better with each cycle of rituximab, when her disease flared it would be worse than the time before, with increasingly higher anti-dsDNA levels recorded. The reason for this seemed to be because of increasing BAFF levels, and so the hypothesis was that if rituximab was associated with increased BAFF levels, then co-targeting BAFF with belimumab should be able to prevent those flares from happening.
The BEAT-LUPUS trial has been a huge collaborative effort and was conducted across 16 U.K. centers. From initial funding to the data analysis, it has taken 6 years to complete and was made possible by a unique partnership between Versus Arthritis, University College London Hospitals Biomedical Research Center, the National Institute for Health Research UK Musculoskeletal Translational Research Collaboration, and GlaxoSmithKline (GSK). GSK provided belimumab free of charge, as well as additional funding, but had no role in the design of the study and will not have any role going forward.
From an initial 172 patients assessed for eligibility, 52 patients were finally enrolled into the trial and received rituximab as two infusions given 2 weeks apart. Patients were then randomized in a double-blind manner to receive either belimumab (n = 26) or placebo (n = 26) 4-8 weeks after their first dose of rituximab. The intention-to-treat population consisted of 43 patients.
The use of belimumab after rituximab did not increase the risk for infection – serious or otherwise – or adverse effects, Dr. Ehrenstein reported. Serious adverse events were reported in six (23%) patients in each arm, and serious infections were seen in two (8%) of the belimumab- and four (15%) of the placebo-treated patients.
“I think the take-home message is that it seems that belimumab can reduce the number of severe flares that occur after rituximab therapy,” Dr. Ehrenstein said. “It’s promising, but not definitive,” he added. The next step is of course to publish these data and to perform a phase 3 trial.
In the discussion time following the presentation, session moderator Xavier Mariette, MD, PhD, of Bicêtre Hospital, Paris-Saclay University, asked why not give belimumab first before rituximab if using belimumab afterward works?
“Our strategy was driven by the observation that BAFF levels surged after rituximab, and therefore it’s logical to give the belimumab to block that BAFF surge,” he answered.
“Certainly, there are ideas that belimumab releases mature B cells into the circulation and rituximab can target that,” he added. That strategy is under investigation in the BLISS-BELIEVE trial, which should also report by the end of this year. It’s a much larger, phase 3 trial, involving nearly 300 patients and is sponsored by GSK.
“Clearly, this is a combination treatment [but] whether you give one before the other is uncertain,” Dr. Ehrenstein observed.
Another member of the viewing audience asked whether it would have been a fairer comparison if another dose of rituximab had been given to patients at week 24 instead of no treatment. Dr. Ehrenstein noted that it was a “good point” to make, but the investigators mainly wanted to answer whether giving belimumab after rituximab would target BAFF and thereby drop serum anti-dsDNA antibody levels. He said that a full trial of rituximab for patients with SLE, perhaps adding this extra dose, needs to be conducted.
Dr. Ehrenstein disclosed receiving research funding and educational grants from GSK and participating in advisory panels for the company.
Using belimumab after rituximab to treat patients with systemic lupus erythematosus (SLE) refractory to conventional therapy not only significantly decreased levels of serum IgG anti-dsDNA antibody levels but also prolonged the time before severe flares of disease occurred in the phase 2b BEAT-LUPUS (Belimumab after B cell depletion in SLE) study.
The trial’s primary outcome of serum IgG anti-dsDNA antibody levels showed a decline from a geometric mean of 162 IU/mL at baseline to 69 IU/mL at 24 weeks and 47 IU/mL at 1 year in patients treated with belimumab (Benlysta) after rituximab (Rituxan and biosimilars). These reductions were significantly lower than the values seen in the placebo after rituximab arm (a respective 121 IU/mL, 99 IU/mL, and 103 IU/mL; P < .001).
Just 3 patients who received belimumab versus 10 who received placebo after rituximab experienced a severe BILAG (British Isles Lupus Assessment Group) index A flare by the end of the study at 52 weeks. The hazard ratio (HR) for the flare reduction was 0.27 (P = .03), indicating a 73% reduction.
The use of belimumab rather than a placebo also led to a small reduction in total serum IgG, and significantly suppressed B-cell repopulation (P = .03).
These results need confirming in a larger, phase 3 trial, the trial’s principal investigator, Michael Ehrenstein, PhD, said at the annual European Congress of Rheumatology. They are “clearly encouraging” and “support the hypothesis that BAFF [B-cell–activating factor] can drive flares after rituximab,” he said.
Although B-cell depletion with rituximab is recommended by national and international guidelines to treat some patients with SLE who are refractory to conventional therapy, its use is not licensed.
“Certainly, rituximab is a controversial drug in lupus,” Dr. Ehrenstein, a consultant rheumatologist based at University College London, said in an interview. Although there is real-world evidence from registries and open-label studies suggesting that it is widely used and effective in some patients, the randomized, controlled trials conducted with rituximab about 10 years ago failed to meet their primary endpoints.
“A lot has been written about why that was, but probably the biggest reason was the high dose of steroids in both groups,” Dr. Ehrenstein said. To try to avoid muddying the waters of the BEAT-LUPUS trial findings, the maximum dose of prednisolone allowed to be used as background therapy was 20 mg/day. The trial’s investigators were also encouraged to reduce the baseline steroid dose to at least 50% by the trial’s 6-month halfway point.
“We tried to reflect what was going on in the U.K.,” Dr. Ehrenstein said, noting that the inspiration for the trial was a patient who had received sequential rituximab treatment. Although she got better with each cycle of rituximab, when her disease flared it would be worse than the time before, with increasingly higher anti-dsDNA levels recorded. The reason for this seemed to be because of increasing BAFF levels, and so the hypothesis was that if rituximab was associated with increased BAFF levels, then co-targeting BAFF with belimumab should be able to prevent those flares from happening.
The BEAT-LUPUS trial has been a huge collaborative effort and was conducted across 16 U.K. centers. From initial funding to the data analysis, it has taken 6 years to complete and was made possible by a unique partnership between Versus Arthritis, University College London Hospitals Biomedical Research Center, the National Institute for Health Research UK Musculoskeletal Translational Research Collaboration, and GlaxoSmithKline (GSK). GSK provided belimumab free of charge, as well as additional funding, but had no role in the design of the study and will not have any role going forward.
From an initial 172 patients assessed for eligibility, 52 patients were finally enrolled into the trial and received rituximab as two infusions given 2 weeks apart. Patients were then randomized in a double-blind manner to receive either belimumab (n = 26) or placebo (n = 26) 4-8 weeks after their first dose of rituximab. The intention-to-treat population consisted of 43 patients.
The use of belimumab after rituximab did not increase the risk for infection – serious or otherwise – or adverse effects, Dr. Ehrenstein reported. Serious adverse events were reported in six (23%) patients in each arm, and serious infections were seen in two (8%) of the belimumab- and four (15%) of the placebo-treated patients.
“I think the take-home message is that it seems that belimumab can reduce the number of severe flares that occur after rituximab therapy,” Dr. Ehrenstein said. “It’s promising, but not definitive,” he added. The next step is of course to publish these data and to perform a phase 3 trial.
In the discussion time following the presentation, session moderator Xavier Mariette, MD, PhD, of Bicêtre Hospital, Paris-Saclay University, asked why not give belimumab first before rituximab if using belimumab afterward works?
“Our strategy was driven by the observation that BAFF levels surged after rituximab, and therefore it’s logical to give the belimumab to block that BAFF surge,” he answered.
“Certainly, there are ideas that belimumab releases mature B cells into the circulation and rituximab can target that,” he added. That strategy is under investigation in the BLISS-BELIEVE trial, which should also report by the end of this year. It’s a much larger, phase 3 trial, involving nearly 300 patients and is sponsored by GSK.
“Clearly, this is a combination treatment [but] whether you give one before the other is uncertain,” Dr. Ehrenstein observed.
Another member of the viewing audience asked whether it would have been a fairer comparison if another dose of rituximab had been given to patients at week 24 instead of no treatment. Dr. Ehrenstein noted that it was a “good point” to make, but the investigators mainly wanted to answer whether giving belimumab after rituximab would target BAFF and thereby drop serum anti-dsDNA antibody levels. He said that a full trial of rituximab for patients with SLE, perhaps adding this extra dose, needs to be conducted.
Dr. Ehrenstein disclosed receiving research funding and educational grants from GSK and participating in advisory panels for the company.
FROM THE EULAR 2021 CONGRESS
Report shows decline in Black ob.gyn. residents from 2014 to 2019
There has been a steady decline in the proportion of Black ob.gyn. residents from 2014 to 2019, according to new research published in JAMA Network Open.
Researchers found that Black residents made up 10.2% of ob.gyn. residents during the 2014-2015 academic year, compared with 7.9% in 2018-2019. Meanwhile, Native American or Alaskan Native and Native Hawaiian or Pacific Islander residents were the least represented in the field, making up just 0.2% of residents in 2014 and 0.1% in 2015.
“When we look at the trend [of Black residents] across several years, it’s surprising that not only is the proportion of [ob.gyn.] Black residents [decreasing], but it was going down at a faster rate than other specialties,” study author Claudia Lopez, MD, said in an interview.
The ob.gyn. specialty tends to have the highest proportion of underrepresented physicians, especially Black and Latino physicians, compared with other specialties, according to a 2016 study published in Obstetrics & Gynecology. This study also found that underrepresented minority ob.gyns. were more likely than White or Asian physicians to practice in underserved areas. However, researchers of the current study found that the decline in Black residents in this field is surprising.
“I do think that ob.gyn. is very unique in that it’s surgical but also has a lot of primary care elements,” Dr. Lopez said. “I think that’s probably why initially our specialty historically has more underrepresented minorities because it combines all those things and [physicians are] so intimate with their patient population.”
Dr. Lopez, resident physician at the University of California, Davis, and colleagues analyzed deidentified data on the race and ethnicity of more than 520,000 residents in ob.gyn., surgical, and nonsurgical specialties from JAMA Medical Education reports from 2014 to 2019.
They found that ob.gyn., surgical, and nonsurgical residents most commonly identified as White, followed by Asian. In addition to the decline in Black ob.gyn. residents, researchers noticed that the proportion of Latino residents remained relatively unchanged. Furthermore, while the racial and ethnic composition of residents varied each year, higher proportions of ob.gyn. residents identified as Black or Latino, compared with those in surgical and nonsurgical specialties.
Researchers noted that, although their findings suggest ob.gyn. residencies have higher proportions of Black and Latino residents, compared with surgical and nonsurgical specialties, the diversity of the ob.gyn. programs lag behind the United States’ changing demographics.
“Medicine in general has a lot to do to match the [U.S. demographic] population,” Dr. Lopez said. “But at least the trend should hopefully be matching, showing some type of progression toward matching our population.”
Gnankang Sarah Napoe, MD, who was not involved in the study, said in an interview that she was saddened by the new findings and believes that if the decline in Black residents continues it would exacerbate racial disparities in obstetric and gynecological care.
“I think recruitment should focus more on specifically recruiting [underrepresented] populations of students into our field, because we know that they are a crucial part of narrowing the health disparities,” said Dr. Napoe, assistant professor* in the department of obstetrics and gynecology and reproductive sciences at the University of Pittsburgh.
Significant health disparities exist within women’s health and ob.gyn. care, with Black, American Indian, and Alaska Native women being two to three times more likely to have a pregnancy-related death than White women, according to the Centers for Disease Control and Prevention.
In an solicited commentary on the study, ob.gyns. from the University of Southern California, Los Angeles, referred to the declining population of Black ob.gyn. residents as “a failure of the medical education system to adapt to the changing demographic needs of its patients and cultivate diversity within the academic pipeline.”
One approach to addressing these health disparities is by increasing the diversity among health care practitioners. A 2020 study published in JAMA Network Open found that a shared identity between the physician and patient is linked to increased patient satisfaction and higher levels of trust.
“We know that, within ob.gyn., there are higher proportions of minority physicians, but just because we know that doesn’t mean that we’re doing everything right,” Dr. Lopez said. “When we look at the bigger picture,we’re not actually seeing the change we want to see. We need to not be complacent and keep evaluating ourselves, because I think that’s how you change.”
The authors and editorialists disclosed no relevant financial relationships.
*This article has been updated to reflect the correct title for Dr. Sarah Napoe.
There has been a steady decline in the proportion of Black ob.gyn. residents from 2014 to 2019, according to new research published in JAMA Network Open.
Researchers found that Black residents made up 10.2% of ob.gyn. residents during the 2014-2015 academic year, compared with 7.9% in 2018-2019. Meanwhile, Native American or Alaskan Native and Native Hawaiian or Pacific Islander residents were the least represented in the field, making up just 0.2% of residents in 2014 and 0.1% in 2015.
“When we look at the trend [of Black residents] across several years, it’s surprising that not only is the proportion of [ob.gyn.] Black residents [decreasing], but it was going down at a faster rate than other specialties,” study author Claudia Lopez, MD, said in an interview.
The ob.gyn. specialty tends to have the highest proportion of underrepresented physicians, especially Black and Latino physicians, compared with other specialties, according to a 2016 study published in Obstetrics & Gynecology. This study also found that underrepresented minority ob.gyns. were more likely than White or Asian physicians to practice in underserved areas. However, researchers of the current study found that the decline in Black residents in this field is surprising.
“I do think that ob.gyn. is very unique in that it’s surgical but also has a lot of primary care elements,” Dr. Lopez said. “I think that’s probably why initially our specialty historically has more underrepresented minorities because it combines all those things and [physicians are] so intimate with their patient population.”
Dr. Lopez, resident physician at the University of California, Davis, and colleagues analyzed deidentified data on the race and ethnicity of more than 520,000 residents in ob.gyn., surgical, and nonsurgical specialties from JAMA Medical Education reports from 2014 to 2019.
They found that ob.gyn., surgical, and nonsurgical residents most commonly identified as White, followed by Asian. In addition to the decline in Black ob.gyn. residents, researchers noticed that the proportion of Latino residents remained relatively unchanged. Furthermore, while the racial and ethnic composition of residents varied each year, higher proportions of ob.gyn. residents identified as Black or Latino, compared with those in surgical and nonsurgical specialties.
Researchers noted that, although their findings suggest ob.gyn. residencies have higher proportions of Black and Latino residents, compared with surgical and nonsurgical specialties, the diversity of the ob.gyn. programs lag behind the United States’ changing demographics.
“Medicine in general has a lot to do to match the [U.S. demographic] population,” Dr. Lopez said. “But at least the trend should hopefully be matching, showing some type of progression toward matching our population.”
Gnankang Sarah Napoe, MD, who was not involved in the study, said in an interview that she was saddened by the new findings and believes that if the decline in Black residents continues it would exacerbate racial disparities in obstetric and gynecological care.
“I think recruitment should focus more on specifically recruiting [underrepresented] populations of students into our field, because we know that they are a crucial part of narrowing the health disparities,” said Dr. Napoe, assistant professor* in the department of obstetrics and gynecology and reproductive sciences at the University of Pittsburgh.
Significant health disparities exist within women’s health and ob.gyn. care, with Black, American Indian, and Alaska Native women being two to three times more likely to have a pregnancy-related death than White women, according to the Centers for Disease Control and Prevention.
In an solicited commentary on the study, ob.gyns. from the University of Southern California, Los Angeles, referred to the declining population of Black ob.gyn. residents as “a failure of the medical education system to adapt to the changing demographic needs of its patients and cultivate diversity within the academic pipeline.”
One approach to addressing these health disparities is by increasing the diversity among health care practitioners. A 2020 study published in JAMA Network Open found that a shared identity between the physician and patient is linked to increased patient satisfaction and higher levels of trust.
“We know that, within ob.gyn., there are higher proportions of minority physicians, but just because we know that doesn’t mean that we’re doing everything right,” Dr. Lopez said. “When we look at the bigger picture,we’re not actually seeing the change we want to see. We need to not be complacent and keep evaluating ourselves, because I think that’s how you change.”
The authors and editorialists disclosed no relevant financial relationships.
*This article has been updated to reflect the correct title for Dr. Sarah Napoe.
There has been a steady decline in the proportion of Black ob.gyn. residents from 2014 to 2019, according to new research published in JAMA Network Open.
Researchers found that Black residents made up 10.2% of ob.gyn. residents during the 2014-2015 academic year, compared with 7.9% in 2018-2019. Meanwhile, Native American or Alaskan Native and Native Hawaiian or Pacific Islander residents were the least represented in the field, making up just 0.2% of residents in 2014 and 0.1% in 2015.
“When we look at the trend [of Black residents] across several years, it’s surprising that not only is the proportion of [ob.gyn.] Black residents [decreasing], but it was going down at a faster rate than other specialties,” study author Claudia Lopez, MD, said in an interview.
The ob.gyn. specialty tends to have the highest proportion of underrepresented physicians, especially Black and Latino physicians, compared with other specialties, according to a 2016 study published in Obstetrics & Gynecology. This study also found that underrepresented minority ob.gyns. were more likely than White or Asian physicians to practice in underserved areas. However, researchers of the current study found that the decline in Black residents in this field is surprising.
“I do think that ob.gyn. is very unique in that it’s surgical but also has a lot of primary care elements,” Dr. Lopez said. “I think that’s probably why initially our specialty historically has more underrepresented minorities because it combines all those things and [physicians are] so intimate with their patient population.”
Dr. Lopez, resident physician at the University of California, Davis, and colleagues analyzed deidentified data on the race and ethnicity of more than 520,000 residents in ob.gyn., surgical, and nonsurgical specialties from JAMA Medical Education reports from 2014 to 2019.
They found that ob.gyn., surgical, and nonsurgical residents most commonly identified as White, followed by Asian. In addition to the decline in Black ob.gyn. residents, researchers noticed that the proportion of Latino residents remained relatively unchanged. Furthermore, while the racial and ethnic composition of residents varied each year, higher proportions of ob.gyn. residents identified as Black or Latino, compared with those in surgical and nonsurgical specialties.
Researchers noted that, although their findings suggest ob.gyn. residencies have higher proportions of Black and Latino residents, compared with surgical and nonsurgical specialties, the diversity of the ob.gyn. programs lag behind the United States’ changing demographics.
“Medicine in general has a lot to do to match the [U.S. demographic] population,” Dr. Lopez said. “But at least the trend should hopefully be matching, showing some type of progression toward matching our population.”
Gnankang Sarah Napoe, MD, who was not involved in the study, said in an interview that she was saddened by the new findings and believes that if the decline in Black residents continues it would exacerbate racial disparities in obstetric and gynecological care.
“I think recruitment should focus more on specifically recruiting [underrepresented] populations of students into our field, because we know that they are a crucial part of narrowing the health disparities,” said Dr. Napoe, assistant professor* in the department of obstetrics and gynecology and reproductive sciences at the University of Pittsburgh.
Significant health disparities exist within women’s health and ob.gyn. care, with Black, American Indian, and Alaska Native women being two to three times more likely to have a pregnancy-related death than White women, according to the Centers for Disease Control and Prevention.
In an solicited commentary on the study, ob.gyns. from the University of Southern California, Los Angeles, referred to the declining population of Black ob.gyn. residents as “a failure of the medical education system to adapt to the changing demographic needs of its patients and cultivate diversity within the academic pipeline.”
One approach to addressing these health disparities is by increasing the diversity among health care practitioners. A 2020 study published in JAMA Network Open found that a shared identity between the physician and patient is linked to increased patient satisfaction and higher levels of trust.
“We know that, within ob.gyn., there are higher proportions of minority physicians, but just because we know that doesn’t mean that we’re doing everything right,” Dr. Lopez said. “When we look at the bigger picture,we’re not actually seeing the change we want to see. We need to not be complacent and keep evaluating ourselves, because I think that’s how you change.”
The authors and editorialists disclosed no relevant financial relationships.
*This article has been updated to reflect the correct title for Dr. Sarah Napoe.
FROM JAMA NETWORK OPEN
Sudden onset of severe pain in left thigh
On the basis of the patient's physical examination, laboratory findings, and radiographic findings, a diagnosis of de novo metastatic prostate cancer is suspected and later confirmed by transrectal ultrasonography–guided needle biopsy of the prostate.
Prostate cancer is the most common cancer and the second most common cause of cancer-associated death in men in the United States. Among men diagnosed with prostate cancer in the United States, approximately three quarters have localized-stage disease at diagnosis; however, recent data show that an increasing number and percentage of men are being diagnosed with distant-stage prostate cancer. Despite advancements in treatment, less than one third of men survive 5 years after the diagnosis of distant-stage prostate cancer.
Prostate cancer frequently metastasizes to the bone. In fact, as many as 90% of patients with advanced prostate cancer have bone involvement. The morbidity from bone metastases is considerable and includes bone pain, immobility, pathologic fractures, hypercalcemia, hematologic disorders, and spinal cord compression. Bone metastases also have a considerable impact on mortality.
In patients with metastatic prostate cancer, determining the presence and extent of metastatic disease is essential for appropriate treatment to be selected. Studies have shown that the extent of metastatic disease affects treatment response. In a recent exploratory analysis of the STAMPEDE trial, survival benefit associated with prostate radiation therapy decreased continuously as the number of bone metastases rose, with the most benefit being seen in patients with up to three bone metastases.
Guidelines recommend that imaging studies be conducted in all patients with advanced prostate cancer. This may include conventional imaging (ie, CT, bone scan, and/or prostate MRI) and/or next-generation imaging (ie, PET, PET/CT, PET/MRI, whole-body MRI). In cases involving hormone-sensitive disease with obvious metastatic disease on conventional imaging at presentation, next-generation imaging may be useful for illuminating the disease burden and possibly shifting the treatment intent from multimodality management of oligometastatic disease to systemic anticancer therapy, either alone or in combination with targeted therapy for palliative purposes. However, prospective data on this are lacking.
Clinicians should also assess symptoms in patients with metastatic hormone-sensitive prostate cancer at presentation, because symptoms have been shown to have prognostic value. In addition, understanding symptoms related to cancer is essential for optimizing pain and other symptom management in addition to anticancer therapy.
Metastatic prostate cancer remains incurable. Immediate systemic treatment with androgen deprivation therapy (ADT) combined with abiraterone acetate plus prednisone or apalutamide or enzalutamide should be offered to symptomatic patients who have distant metastases on diagnosis, both to alleviate symptoms and to lessen the risk for potential serious complications, such as spinal cord compression. ADT combined with docetaxel can also be offered to patients who are able to tolerate docetaxel.
ADT combined with prostate radiation therapy may be offered to patients with distant metastases and low-volume disease. However, when patients present with high-volume disease, referral to a clinical trial is recommended.
Surgery and/or local radiation therapy can be considered for patients with distant metastases and evidence of impending complications (eg, spinal cord compression or pathologic fracture).
Kyle A. Richards, MD, Assistant Professor, Department of Urology, University of Wisconsin-Madison; Chief of Urology, William S. Middleton Memorial VA Hospital, Madison, Wisconsin.
Kyle A. Richards, MD, has disclosed no relevant financial relationships.
On the basis of the patient's physical examination, laboratory findings, and radiographic findings, a diagnosis of de novo metastatic prostate cancer is suspected and later confirmed by transrectal ultrasonography–guided needle biopsy of the prostate.
Prostate cancer is the most common cancer and the second most common cause of cancer-associated death in men in the United States. Among men diagnosed with prostate cancer in the United States, approximately three quarters have localized-stage disease at diagnosis; however, recent data show that an increasing number and percentage of men are being diagnosed with distant-stage prostate cancer. Despite advancements in treatment, less than one third of men survive 5 years after the diagnosis of distant-stage prostate cancer.
Prostate cancer frequently metastasizes to the bone. In fact, as many as 90% of patients with advanced prostate cancer have bone involvement. The morbidity from bone metastases is considerable and includes bone pain, immobility, pathologic fractures, hypercalcemia, hematologic disorders, and spinal cord compression. Bone metastases also have a considerable impact on mortality.
In patients with metastatic prostate cancer, determining the presence and extent of metastatic disease is essential for appropriate treatment to be selected. Studies have shown that the extent of metastatic disease affects treatment response. In a recent exploratory analysis of the STAMPEDE trial, survival benefit associated with prostate radiation therapy decreased continuously as the number of bone metastases rose, with the most benefit being seen in patients with up to three bone metastases.
Guidelines recommend that imaging studies be conducted in all patients with advanced prostate cancer. This may include conventional imaging (ie, CT, bone scan, and/or prostate MRI) and/or next-generation imaging (ie, PET, PET/CT, PET/MRI, whole-body MRI). In cases involving hormone-sensitive disease with obvious metastatic disease on conventional imaging at presentation, next-generation imaging may be useful for illuminating the disease burden and possibly shifting the treatment intent from multimodality management of oligometastatic disease to systemic anticancer therapy, either alone or in combination with targeted therapy for palliative purposes. However, prospective data on this are lacking.
Clinicians should also assess symptoms in patients with metastatic hormone-sensitive prostate cancer at presentation, because symptoms have been shown to have prognostic value. In addition, understanding symptoms related to cancer is essential for optimizing pain and other symptom management in addition to anticancer therapy.
Metastatic prostate cancer remains incurable. Immediate systemic treatment with androgen deprivation therapy (ADT) combined with abiraterone acetate plus prednisone or apalutamide or enzalutamide should be offered to symptomatic patients who have distant metastases on diagnosis, both to alleviate symptoms and to lessen the risk for potential serious complications, such as spinal cord compression. ADT combined with docetaxel can also be offered to patients who are able to tolerate docetaxel.
ADT combined with prostate radiation therapy may be offered to patients with distant metastases and low-volume disease. However, when patients present with high-volume disease, referral to a clinical trial is recommended.
Surgery and/or local radiation therapy can be considered for patients with distant metastases and evidence of impending complications (eg, spinal cord compression or pathologic fracture).
Kyle A. Richards, MD, Assistant Professor, Department of Urology, University of Wisconsin-Madison; Chief of Urology, William S. Middleton Memorial VA Hospital, Madison, Wisconsin.
Kyle A. Richards, MD, has disclosed no relevant financial relationships.
On the basis of the patient's physical examination, laboratory findings, and radiographic findings, a diagnosis of de novo metastatic prostate cancer is suspected and later confirmed by transrectal ultrasonography–guided needle biopsy of the prostate.
Prostate cancer is the most common cancer and the second most common cause of cancer-associated death in men in the United States. Among men diagnosed with prostate cancer in the United States, approximately three quarters have localized-stage disease at diagnosis; however, recent data show that an increasing number and percentage of men are being diagnosed with distant-stage prostate cancer. Despite advancements in treatment, less than one third of men survive 5 years after the diagnosis of distant-stage prostate cancer.
Prostate cancer frequently metastasizes to the bone. In fact, as many as 90% of patients with advanced prostate cancer have bone involvement. The morbidity from bone metastases is considerable and includes bone pain, immobility, pathologic fractures, hypercalcemia, hematologic disorders, and spinal cord compression. Bone metastases also have a considerable impact on mortality.
In patients with metastatic prostate cancer, determining the presence and extent of metastatic disease is essential for appropriate treatment to be selected. Studies have shown that the extent of metastatic disease affects treatment response. In a recent exploratory analysis of the STAMPEDE trial, survival benefit associated with prostate radiation therapy decreased continuously as the number of bone metastases rose, with the most benefit being seen in patients with up to three bone metastases.
Guidelines recommend that imaging studies be conducted in all patients with advanced prostate cancer. This may include conventional imaging (ie, CT, bone scan, and/or prostate MRI) and/or next-generation imaging (ie, PET, PET/CT, PET/MRI, whole-body MRI). In cases involving hormone-sensitive disease with obvious metastatic disease on conventional imaging at presentation, next-generation imaging may be useful for illuminating the disease burden and possibly shifting the treatment intent from multimodality management of oligometastatic disease to systemic anticancer therapy, either alone or in combination with targeted therapy for palliative purposes. However, prospective data on this are lacking.
Clinicians should also assess symptoms in patients with metastatic hormone-sensitive prostate cancer at presentation, because symptoms have been shown to have prognostic value. In addition, understanding symptoms related to cancer is essential for optimizing pain and other symptom management in addition to anticancer therapy.
Metastatic prostate cancer remains incurable. Immediate systemic treatment with androgen deprivation therapy (ADT) combined with abiraterone acetate plus prednisone or apalutamide or enzalutamide should be offered to symptomatic patients who have distant metastases on diagnosis, both to alleviate symptoms and to lessen the risk for potential serious complications, such as spinal cord compression. ADT combined with docetaxel can also be offered to patients who are able to tolerate docetaxel.
ADT combined with prostate radiation therapy may be offered to patients with distant metastases and low-volume disease. However, when patients present with high-volume disease, referral to a clinical trial is recommended.
Surgery and/or local radiation therapy can be considered for patients with distant metastases and evidence of impending complications (eg, spinal cord compression or pathologic fracture).
Kyle A. Richards, MD, Assistant Professor, Department of Urology, University of Wisconsin-Madison; Chief of Urology, William S. Middleton Memorial VA Hospital, Madison, Wisconsin.
Kyle A. Richards, MD, has disclosed no relevant financial relationships.
A 74-year-old man presents to the emergency department with sudden onset of severe pain in his left thigh, a 3-month history of unexplained weight loss and general weakness, and progressive difficulty in walking for the past 3 weeks. The patient states that he has always been in excellent health and he has not seen a physician in at least 10 years. Cachexia is noted on physical examination. Laboratory findings include hemoglobin, 12.4 g/dL; white blood cells, 8.12 cells/µL; platelets, 310,000 cells/µL; creatinine, 1.4 mg/dL; sodium, 137 mmol/L; potassium, 4.4 mmol/L; calcium, 10.1 mg/dL; prostate-specific antigen, 31 ng/mL; aspartate aminotransferase, 37 IU/L; and gamma-glutamyltransferase, 16 IU/L. Proteinuria and hematuria are detected by urinalysis. CT reveals multiple diffuse osteoblastic lesions in the right proximal femur.
