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Do adolescents develop CNS autoimmunity after COVID-19?
Recent research suggests that some pediatric patients who develop neuropsychiatric symptoms from COVID-19 may have intrathecal antineural SARS-CoV-2 autoantibodies, which may hint at central nervous system (CNS) autoimmunity in these patients.
“Overall, these findings indicate that severe neuropsychiatric symptoms can occur in the setting of pediatric COVID-19, including patients who lack many of the cardinal systemic features,” Christopher M. Bartley, MD, PhD, of the Weill Institute for Neurosciences at the University of California, San Francisco, and colleagues wrote in their study. “These data highlight the possibility of SARS-CoV-2 neuroinvasion and/or CNS autoimmunity in pediatric patients with COVID-19 and neuropsychiatric symptoms.”
In a case series published Oct. 25 in JAMA Neurology (doi: 10.1001/jamaneurol.2021.3821), Dr. Bartley and colleagues examined three pediatric patients who were infected with SARS-CoV-2 and, over a period of 5 months in 2020, were admitted to the hospital – where they received a neurology consultation for “subacute, functionally impairing behavioral changes.”
Patient 1 had a history of unspecified anxiety and depression, and was admitted for erratic behavior, paranoia-like fears, social withdrawal, and insomnia. The patient did not respond to treatment with risperidone and gabapentin, and was readmitted soon after discharge, then treated with olanzapine followed by a transition to valproate and lorazepam. It was found the patient had cerebrospinal fluid (CSF) abnormalities in the form of elevated protein levels, and an elevated IgG index, and was given intravenous immunoglobulin followed by IV methylprednisolone. While symptoms such as paranoia improved and the patient was able to better organize thoughts after 5 days, other symptoms such as delusions and hyperreflexia persisted for at least 1 month before resolving, and some symptoms, such as lability, did not resolve before discharge.
Patient 2 had a history of motor tics and anxiety, but showed signs of insomnia, mood lability, impaired concentration, difficulty finding words, and problems completing homework following a SARS-CoV-2 infection. The patient’s father previously had been diagnosed with COVID-19 and the patient developed respiratory symptoms and fever; an IgG serology test later confirmed a SARS-CoV-2 infection. The patient went on to experience internal preoccupation, aggression, and suicidal ideation. The patients was treated with aripiprazole and risperidone, but did not respond, and was admitted to the hospital. As with patient 1, patient 2 had CSF abnormalities in the form of elevated protein levels, and responded to IV methylprednisolone, with working memory and bradyphrenia improving. However, the patient developed insomnia, extreme anxiety, suicidal ideation, aggression, and sadness after discharge, and was readmitted. The patient was treated with IV immunoglobulin, and discharged with quetiapine and lithium.
“Six months later, although improved from initial presentation, the patient required academic accommodations and continued to endorse forgetfulness and attention difficulties. The patient’s chronic tics and anxiety were unchanged,” Dr. Bartley and colleagues wrote.
Patient 3 had no psychiatric history but started to demonstrate “odd behavior, including repetitive behaviors, anorexia, and insomnia” following a SARS-CoV-2 infection. After being hospitalized, the patient showed signs of “ideomotor apraxia, abulia, disorganized behavior, agitation, and diffusely brisk reflexes” and had a high white blood cell count, creatine kinase level, and C-reactive protein level. CSF was also abnormal for this patient, with three unique oligoclonal bands identified. The patient was treated with lorazepam and olanzapine, did not receive immunotherapy, and was discharged without psychiatric medications after 4 days.
When the researchers performed testing on each of the three patients, they found intrathecal anti–SARS-CoV-2 IgG and immunostained mouse brain tissue, and “a diverse set of candidate autoantigens by human phage immunoprecipitation sequencing” in patient 1 and patient 2. In comparison, patient 3 “neither appreciably immunostained nor enriched candidates by human phage immunoprecipitation sequencing,” the researchers said.
“ and the potential for immunotherapy in some,” Dr. Bartley and colleagues concluded.
Potential of CNS autoimmunity
Evan J. Kyzar, MD, PhD, a resident physician in psychiatry at New York State Psychiatric Institute in New York Presbyterian–Columbia Campus, said in an interview that the results of the case series show some pediatric patients with neuropsychiatric symptoms can have anti-SARS-CoV-2 antibodies after viral clearance.
“Interestingly, some of the patients in this study also had antibodies in the CSF that targeted native proteins, demonstrating that COVID-19 may lead to autoimmunity directed at the brain,” he said. “This study increases our knowledge of how COVID-19 interacts with the nervous system and how autoimmune mechanisms might be contributing to at least a portion of patients with neuropsychiatric symptoms during acute infection, and possibly even after viral clearance.”
Dr. Kyzar noted that the immunological methods in the study were “cutting-edge” and the validation exploring the immune responses was detailed, but was limited because of the small sample size.
“[T]he researchers are using similar techniques to explore psychiatric disorders such as depression and schizophrenia to determine if some patients diagnosed with these conditions may have CNS-targeting autoantibodies that contribute to their symptoms and clinical presentation,” Dr. Kyzar said. “This work has the potential to discover novel neuroimmune mechanisms contributing to neuropsychiatric disease and offer possible pathways for the discovery of new treatments.”
The authors reported financial relationships with Allen & Company, the Chan Zuckerberg Initiative, National Institutes of Health, Novartis, Public Health Company, Roche/Genentech, Sandler Foundation, and Takeda in the form of grants and personal fees. They reported funding and/or support from the Brain Research Foundation, Hanna H. Gray Fellowship, Howard Hughes Medical Institute, John A. Watson Scholar Program, Latinx Center of Excellence, the National Institute of Mental Health, the National Institute of Neurological Disorders and Stroke, President’s Postdoctoral Fellowship Program, and Shared Instrumentation grant. Dr. Kyzar reported no relevant financial disclosures.
Recent research suggests that some pediatric patients who develop neuropsychiatric symptoms from COVID-19 may have intrathecal antineural SARS-CoV-2 autoantibodies, which may hint at central nervous system (CNS) autoimmunity in these patients.
“Overall, these findings indicate that severe neuropsychiatric symptoms can occur in the setting of pediatric COVID-19, including patients who lack many of the cardinal systemic features,” Christopher M. Bartley, MD, PhD, of the Weill Institute for Neurosciences at the University of California, San Francisco, and colleagues wrote in their study. “These data highlight the possibility of SARS-CoV-2 neuroinvasion and/or CNS autoimmunity in pediatric patients with COVID-19 and neuropsychiatric symptoms.”
In a case series published Oct. 25 in JAMA Neurology (doi: 10.1001/jamaneurol.2021.3821), Dr. Bartley and colleagues examined three pediatric patients who were infected with SARS-CoV-2 and, over a period of 5 months in 2020, were admitted to the hospital – where they received a neurology consultation for “subacute, functionally impairing behavioral changes.”
Patient 1 had a history of unspecified anxiety and depression, and was admitted for erratic behavior, paranoia-like fears, social withdrawal, and insomnia. The patient did not respond to treatment with risperidone and gabapentin, and was readmitted soon after discharge, then treated with olanzapine followed by a transition to valproate and lorazepam. It was found the patient had cerebrospinal fluid (CSF) abnormalities in the form of elevated protein levels, and an elevated IgG index, and was given intravenous immunoglobulin followed by IV methylprednisolone. While symptoms such as paranoia improved and the patient was able to better organize thoughts after 5 days, other symptoms such as delusions and hyperreflexia persisted for at least 1 month before resolving, and some symptoms, such as lability, did not resolve before discharge.
Patient 2 had a history of motor tics and anxiety, but showed signs of insomnia, mood lability, impaired concentration, difficulty finding words, and problems completing homework following a SARS-CoV-2 infection. The patient’s father previously had been diagnosed with COVID-19 and the patient developed respiratory symptoms and fever; an IgG serology test later confirmed a SARS-CoV-2 infection. The patient went on to experience internal preoccupation, aggression, and suicidal ideation. The patients was treated with aripiprazole and risperidone, but did not respond, and was admitted to the hospital. As with patient 1, patient 2 had CSF abnormalities in the form of elevated protein levels, and responded to IV methylprednisolone, with working memory and bradyphrenia improving. However, the patient developed insomnia, extreme anxiety, suicidal ideation, aggression, and sadness after discharge, and was readmitted. The patient was treated with IV immunoglobulin, and discharged with quetiapine and lithium.
“Six months later, although improved from initial presentation, the patient required academic accommodations and continued to endorse forgetfulness and attention difficulties. The patient’s chronic tics and anxiety were unchanged,” Dr. Bartley and colleagues wrote.
Patient 3 had no psychiatric history but started to demonstrate “odd behavior, including repetitive behaviors, anorexia, and insomnia” following a SARS-CoV-2 infection. After being hospitalized, the patient showed signs of “ideomotor apraxia, abulia, disorganized behavior, agitation, and diffusely brisk reflexes” and had a high white blood cell count, creatine kinase level, and C-reactive protein level. CSF was also abnormal for this patient, with three unique oligoclonal bands identified. The patient was treated with lorazepam and olanzapine, did not receive immunotherapy, and was discharged without psychiatric medications after 4 days.
When the researchers performed testing on each of the three patients, they found intrathecal anti–SARS-CoV-2 IgG and immunostained mouse brain tissue, and “a diverse set of candidate autoantigens by human phage immunoprecipitation sequencing” in patient 1 and patient 2. In comparison, patient 3 “neither appreciably immunostained nor enriched candidates by human phage immunoprecipitation sequencing,” the researchers said.
“ and the potential for immunotherapy in some,” Dr. Bartley and colleagues concluded.
Potential of CNS autoimmunity
Evan J. Kyzar, MD, PhD, a resident physician in psychiatry at New York State Psychiatric Institute in New York Presbyterian–Columbia Campus, said in an interview that the results of the case series show some pediatric patients with neuropsychiatric symptoms can have anti-SARS-CoV-2 antibodies after viral clearance.
“Interestingly, some of the patients in this study also had antibodies in the CSF that targeted native proteins, demonstrating that COVID-19 may lead to autoimmunity directed at the brain,” he said. “This study increases our knowledge of how COVID-19 interacts with the nervous system and how autoimmune mechanisms might be contributing to at least a portion of patients with neuropsychiatric symptoms during acute infection, and possibly even after viral clearance.”
Dr. Kyzar noted that the immunological methods in the study were “cutting-edge” and the validation exploring the immune responses was detailed, but was limited because of the small sample size.
“[T]he researchers are using similar techniques to explore psychiatric disorders such as depression and schizophrenia to determine if some patients diagnosed with these conditions may have CNS-targeting autoantibodies that contribute to their symptoms and clinical presentation,” Dr. Kyzar said. “This work has the potential to discover novel neuroimmune mechanisms contributing to neuropsychiatric disease and offer possible pathways for the discovery of new treatments.”
The authors reported financial relationships with Allen & Company, the Chan Zuckerberg Initiative, National Institutes of Health, Novartis, Public Health Company, Roche/Genentech, Sandler Foundation, and Takeda in the form of grants and personal fees. They reported funding and/or support from the Brain Research Foundation, Hanna H. Gray Fellowship, Howard Hughes Medical Institute, John A. Watson Scholar Program, Latinx Center of Excellence, the National Institute of Mental Health, the National Institute of Neurological Disorders and Stroke, President’s Postdoctoral Fellowship Program, and Shared Instrumentation grant. Dr. Kyzar reported no relevant financial disclosures.
Recent research suggests that some pediatric patients who develop neuropsychiatric symptoms from COVID-19 may have intrathecal antineural SARS-CoV-2 autoantibodies, which may hint at central nervous system (CNS) autoimmunity in these patients.
“Overall, these findings indicate that severe neuropsychiatric symptoms can occur in the setting of pediatric COVID-19, including patients who lack many of the cardinal systemic features,” Christopher M. Bartley, MD, PhD, of the Weill Institute for Neurosciences at the University of California, San Francisco, and colleagues wrote in their study. “These data highlight the possibility of SARS-CoV-2 neuroinvasion and/or CNS autoimmunity in pediatric patients with COVID-19 and neuropsychiatric symptoms.”
In a case series published Oct. 25 in JAMA Neurology (doi: 10.1001/jamaneurol.2021.3821), Dr. Bartley and colleagues examined three pediatric patients who were infected with SARS-CoV-2 and, over a period of 5 months in 2020, were admitted to the hospital – where they received a neurology consultation for “subacute, functionally impairing behavioral changes.”
Patient 1 had a history of unspecified anxiety and depression, and was admitted for erratic behavior, paranoia-like fears, social withdrawal, and insomnia. The patient did not respond to treatment with risperidone and gabapentin, and was readmitted soon after discharge, then treated with olanzapine followed by a transition to valproate and lorazepam. It was found the patient had cerebrospinal fluid (CSF) abnormalities in the form of elevated protein levels, and an elevated IgG index, and was given intravenous immunoglobulin followed by IV methylprednisolone. While symptoms such as paranoia improved and the patient was able to better organize thoughts after 5 days, other symptoms such as delusions and hyperreflexia persisted for at least 1 month before resolving, and some symptoms, such as lability, did not resolve before discharge.
Patient 2 had a history of motor tics and anxiety, but showed signs of insomnia, mood lability, impaired concentration, difficulty finding words, and problems completing homework following a SARS-CoV-2 infection. The patient’s father previously had been diagnosed with COVID-19 and the patient developed respiratory symptoms and fever; an IgG serology test later confirmed a SARS-CoV-2 infection. The patient went on to experience internal preoccupation, aggression, and suicidal ideation. The patients was treated with aripiprazole and risperidone, but did not respond, and was admitted to the hospital. As with patient 1, patient 2 had CSF abnormalities in the form of elevated protein levels, and responded to IV methylprednisolone, with working memory and bradyphrenia improving. However, the patient developed insomnia, extreme anxiety, suicidal ideation, aggression, and sadness after discharge, and was readmitted. The patient was treated with IV immunoglobulin, and discharged with quetiapine and lithium.
“Six months later, although improved from initial presentation, the patient required academic accommodations and continued to endorse forgetfulness and attention difficulties. The patient’s chronic tics and anxiety were unchanged,” Dr. Bartley and colleagues wrote.
Patient 3 had no psychiatric history but started to demonstrate “odd behavior, including repetitive behaviors, anorexia, and insomnia” following a SARS-CoV-2 infection. After being hospitalized, the patient showed signs of “ideomotor apraxia, abulia, disorganized behavior, agitation, and diffusely brisk reflexes” and had a high white blood cell count, creatine kinase level, and C-reactive protein level. CSF was also abnormal for this patient, with three unique oligoclonal bands identified. The patient was treated with lorazepam and olanzapine, did not receive immunotherapy, and was discharged without psychiatric medications after 4 days.
When the researchers performed testing on each of the three patients, they found intrathecal anti–SARS-CoV-2 IgG and immunostained mouse brain tissue, and “a diverse set of candidate autoantigens by human phage immunoprecipitation sequencing” in patient 1 and patient 2. In comparison, patient 3 “neither appreciably immunostained nor enriched candidates by human phage immunoprecipitation sequencing,” the researchers said.
“ and the potential for immunotherapy in some,” Dr. Bartley and colleagues concluded.
Potential of CNS autoimmunity
Evan J. Kyzar, MD, PhD, a resident physician in psychiatry at New York State Psychiatric Institute in New York Presbyterian–Columbia Campus, said in an interview that the results of the case series show some pediatric patients with neuropsychiatric symptoms can have anti-SARS-CoV-2 antibodies after viral clearance.
“Interestingly, some of the patients in this study also had antibodies in the CSF that targeted native proteins, demonstrating that COVID-19 may lead to autoimmunity directed at the brain,” he said. “This study increases our knowledge of how COVID-19 interacts with the nervous system and how autoimmune mechanisms might be contributing to at least a portion of patients with neuropsychiatric symptoms during acute infection, and possibly even after viral clearance.”
Dr. Kyzar noted that the immunological methods in the study were “cutting-edge” and the validation exploring the immune responses was detailed, but was limited because of the small sample size.
“[T]he researchers are using similar techniques to explore psychiatric disorders such as depression and schizophrenia to determine if some patients diagnosed with these conditions may have CNS-targeting autoantibodies that contribute to their symptoms and clinical presentation,” Dr. Kyzar said. “This work has the potential to discover novel neuroimmune mechanisms contributing to neuropsychiatric disease and offer possible pathways for the discovery of new treatments.”
The authors reported financial relationships with Allen & Company, the Chan Zuckerberg Initiative, National Institutes of Health, Novartis, Public Health Company, Roche/Genentech, Sandler Foundation, and Takeda in the form of grants and personal fees. They reported funding and/or support from the Brain Research Foundation, Hanna H. Gray Fellowship, Howard Hughes Medical Institute, John A. Watson Scholar Program, Latinx Center of Excellence, the National Institute of Mental Health, the National Institute of Neurological Disorders and Stroke, President’s Postdoctoral Fellowship Program, and Shared Instrumentation grant. Dr. Kyzar reported no relevant financial disclosures.
FROM JAMA NEUROLOGY
Higher odds for preterm, C-section births seen in women with PsA
Disease-modifying antirheumatic drugs (DMARDs) such as biologics may carry an increased risk for preterm birth or cesarean delivery for pregnant women with psoriatic arthritis (PsA), according to a recent study published in Arthritis & Rheumatology.
The risk was particularly high for women with PsA who received biologic disease-modifying antirheumatic drugs (bDMARDs), according to Katarina Remaeus, PhD, of the Karolinska Institute in Stockholm and colleagues.
“The results may indicate that a more severe or active PsA disease that requires antirheumatic treatment during pregnancy, especially bDMARDs, is associated with increased risks of adverse pregnancy outcomes compared to non-PsA pregnancies,” Dr. Remaeus and colleagues write in their study. “The risk of preterm birth in PsA pregnancies is further influenced by parity with the most increased risks observed in first pregnancies.”
In a nationwide, register-based cohort study, the researchers evaluated 921 pregnancies of women with PsA between 2007 and 2017, comparing them to the pregnancies of 9,210 women without PsA over the same time frame. The pregnancies for women with PsA were further categorized based on whether the women had not received antirheumatic treatment in the year prior to and/or during pregnancy (495 pregnancies) or had received antirheumatic treatment at any point in the year before and/or during pregnancy (426 pregnancies).
Of the women in the PsA group who were treated in the year prior to pregnancy (170 women), 39.4% received monotherapy with a conventional synthetic DMARD (csDMARD) such as an antimalarial, methotrexate, or sulfasalazine; 24.1% received oral corticosteroids, and 15.9% received a tumor necrosis factor inhibitor (TNFi), whereas about 20% of women received two or more antirheumatic drugs.
In the group of women treated during pregnancy (256 women), 153 did not receive bDMARDs; of these, 41.8% had monotherapy with either a csDMARD or corticosteroids, whereas the group treated with bDMARDs received TNFi monotherapy (43.7%) or TNFi with corticosteroids (35.9%), TNFi with csDMARD (9.7%), or TNFi with csDMARD plus corticosteroids (9.7%).
A majority of women in both groups (70.1%) were between ages 30 and 34 years (37.1%) or older than age 35 years (33%) and had delivered more than one child (63.2%). Women in the PsA group were more likely to be born in a Nordic country (91.8% vs. 82.8%), to have a body mass index between 30.0 and 60.0 kg/m2 (19.9% vs. 12.6%), to be a smoker (9.2% vs. 5.3%), to have hypertension (1.4% vs. 0.8%) or diabetes (1.3% vs. 0.5%) prior to pregnancy, and to have a higher level of education (>12 years; 50.1% vs. 43.3%), compared with women in the non-PsA group.
The results showed women in the PsA group were more likely to experience preterm birth (adjusted odds ratio, 1.69; 95% confidence interval, 1.27-2.24) and undergo an elective (aOR, 1.77; 95% CI, 1.43-2.20) or emergency C-section (aOR, 1.42; 95% CI, 1.10-1.84). The group at highest risk for preterm birth with regard to parity was women with PsA having their first child (aOR, 3.95; 95% CI, 1.43-10.95).
Women who received antirheumatic treatment were at greater risk for experiencing preterm birth (aOR, 2.30; 95% CI, 1.49-3.56), and this risk was even higher for treatment with bDMARDs, compared with women without PsA (aOR, 4.49; 95% CI, 2.60-7.79). Use of bDMARDs also was associated with higher risks for spontaneous preterm birth (aOR, 4.73; 95% CI, 2.53-8.87), preterm birth between 32 and 36 weeks’ gestation (aOR, 5.06; 95% CI, 2.91-8.79), elective C-section (aOR, 2.72; 95% CI, 1.61-4.59), emergency C-section (aOR, 2.06; 95% CI, 1.04-4.07), and preeclampsia (aOR, 2.88, 95% CI, 1.35-6.17).
The researchers note that women with PsA should be evaluated for preterm birth particularly if they are having their first child, and “from a clinical point of view, all women with PsA, regardless of antirheumatic treatment, should be counseled about pregnancy outcomes and receive individualized monitoring during pregnancy.”
Are adverse outcomes linked to disease activity or treatment?
Patients in the study had a higher risk of adverse outcomes when they had a PsA diagnosis, and when they received antirheumatic treatment – but were the adverse outcomes associated with a patient’s high disease activity or need for antirheumatic treatment?
“Our interpretation is that a PsA disease that requires continued antirheumatic treatment during pregnancy is more severe than PsA that does not require treatment,” Dr. Remaeus and colleagues write. “Thus, the increased risk of adverse outcomes in pregnancies with maternal antirheumatic treatment is probably attributed to disease severity rather than an effect of the medication itself.”
Anja Strangfeld, MD, PhD, of the German Rheumatism Research Centre in Berlin, told this news organization that the results of the study are important because it is one of the first to report differences in risk in pregnancy outcomes for women with and without PsA.
“The information is relevant to guide rheumatologists in advising patients with PsA when planning the first or subsequent pregnancies,” she said. “The results are reassuring in reporting that the elevated risk for PsA patients for adverse pregnancy outcomes is low in patients not in need of antirheumatic medication, presumably in low-disease activity.”
However, the study is still unclear on whether the association with adverse pregnancy outcomes in patients is the result of higher disease activity or the need for antirheumatic treatment, she explained.
“It was only hypothesized that those patients under bDMARD treatment are/were in high disease activity. There [is] no information on disease activity in the data sources, which limits the results,” she said. “The investigation still does not solve the important question – if adverse pregnancy outcomes are rather related to high disease activity or the medication to treat this situation.”
There was no specific funding for this study. The study authors and Dr. Strangfeld have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Disease-modifying antirheumatic drugs (DMARDs) such as biologics may carry an increased risk for preterm birth or cesarean delivery for pregnant women with psoriatic arthritis (PsA), according to a recent study published in Arthritis & Rheumatology.
The risk was particularly high for women with PsA who received biologic disease-modifying antirheumatic drugs (bDMARDs), according to Katarina Remaeus, PhD, of the Karolinska Institute in Stockholm and colleagues.
“The results may indicate that a more severe or active PsA disease that requires antirheumatic treatment during pregnancy, especially bDMARDs, is associated with increased risks of adverse pregnancy outcomes compared to non-PsA pregnancies,” Dr. Remaeus and colleagues write in their study. “The risk of preterm birth in PsA pregnancies is further influenced by parity with the most increased risks observed in first pregnancies.”
In a nationwide, register-based cohort study, the researchers evaluated 921 pregnancies of women with PsA between 2007 and 2017, comparing them to the pregnancies of 9,210 women without PsA over the same time frame. The pregnancies for women with PsA were further categorized based on whether the women had not received antirheumatic treatment in the year prior to and/or during pregnancy (495 pregnancies) or had received antirheumatic treatment at any point in the year before and/or during pregnancy (426 pregnancies).
Of the women in the PsA group who were treated in the year prior to pregnancy (170 women), 39.4% received monotherapy with a conventional synthetic DMARD (csDMARD) such as an antimalarial, methotrexate, or sulfasalazine; 24.1% received oral corticosteroids, and 15.9% received a tumor necrosis factor inhibitor (TNFi), whereas about 20% of women received two or more antirheumatic drugs.
In the group of women treated during pregnancy (256 women), 153 did not receive bDMARDs; of these, 41.8% had monotherapy with either a csDMARD or corticosteroids, whereas the group treated with bDMARDs received TNFi monotherapy (43.7%) or TNFi with corticosteroids (35.9%), TNFi with csDMARD (9.7%), or TNFi with csDMARD plus corticosteroids (9.7%).
A majority of women in both groups (70.1%) were between ages 30 and 34 years (37.1%) or older than age 35 years (33%) and had delivered more than one child (63.2%). Women in the PsA group were more likely to be born in a Nordic country (91.8% vs. 82.8%), to have a body mass index between 30.0 and 60.0 kg/m2 (19.9% vs. 12.6%), to be a smoker (9.2% vs. 5.3%), to have hypertension (1.4% vs. 0.8%) or diabetes (1.3% vs. 0.5%) prior to pregnancy, and to have a higher level of education (>12 years; 50.1% vs. 43.3%), compared with women in the non-PsA group.
The results showed women in the PsA group were more likely to experience preterm birth (adjusted odds ratio, 1.69; 95% confidence interval, 1.27-2.24) and undergo an elective (aOR, 1.77; 95% CI, 1.43-2.20) or emergency C-section (aOR, 1.42; 95% CI, 1.10-1.84). The group at highest risk for preterm birth with regard to parity was women with PsA having their first child (aOR, 3.95; 95% CI, 1.43-10.95).
Women who received antirheumatic treatment were at greater risk for experiencing preterm birth (aOR, 2.30; 95% CI, 1.49-3.56), and this risk was even higher for treatment with bDMARDs, compared with women without PsA (aOR, 4.49; 95% CI, 2.60-7.79). Use of bDMARDs also was associated with higher risks for spontaneous preterm birth (aOR, 4.73; 95% CI, 2.53-8.87), preterm birth between 32 and 36 weeks’ gestation (aOR, 5.06; 95% CI, 2.91-8.79), elective C-section (aOR, 2.72; 95% CI, 1.61-4.59), emergency C-section (aOR, 2.06; 95% CI, 1.04-4.07), and preeclampsia (aOR, 2.88, 95% CI, 1.35-6.17).
The researchers note that women with PsA should be evaluated for preterm birth particularly if they are having their first child, and “from a clinical point of view, all women with PsA, regardless of antirheumatic treatment, should be counseled about pregnancy outcomes and receive individualized monitoring during pregnancy.”
Are adverse outcomes linked to disease activity or treatment?
Patients in the study had a higher risk of adverse outcomes when they had a PsA diagnosis, and when they received antirheumatic treatment – but were the adverse outcomes associated with a patient’s high disease activity or need for antirheumatic treatment?
“Our interpretation is that a PsA disease that requires continued antirheumatic treatment during pregnancy is more severe than PsA that does not require treatment,” Dr. Remaeus and colleagues write. “Thus, the increased risk of adverse outcomes in pregnancies with maternal antirheumatic treatment is probably attributed to disease severity rather than an effect of the medication itself.”
Anja Strangfeld, MD, PhD, of the German Rheumatism Research Centre in Berlin, told this news organization that the results of the study are important because it is one of the first to report differences in risk in pregnancy outcomes for women with and without PsA.
“The information is relevant to guide rheumatologists in advising patients with PsA when planning the first or subsequent pregnancies,” she said. “The results are reassuring in reporting that the elevated risk for PsA patients for adverse pregnancy outcomes is low in patients not in need of antirheumatic medication, presumably in low-disease activity.”
However, the study is still unclear on whether the association with adverse pregnancy outcomes in patients is the result of higher disease activity or the need for antirheumatic treatment, she explained.
“It was only hypothesized that those patients under bDMARD treatment are/were in high disease activity. There [is] no information on disease activity in the data sources, which limits the results,” she said. “The investigation still does not solve the important question – if adverse pregnancy outcomes are rather related to high disease activity or the medication to treat this situation.”
There was no specific funding for this study. The study authors and Dr. Strangfeld have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Disease-modifying antirheumatic drugs (DMARDs) such as biologics may carry an increased risk for preterm birth or cesarean delivery for pregnant women with psoriatic arthritis (PsA), according to a recent study published in Arthritis & Rheumatology.
The risk was particularly high for women with PsA who received biologic disease-modifying antirheumatic drugs (bDMARDs), according to Katarina Remaeus, PhD, of the Karolinska Institute in Stockholm and colleagues.
“The results may indicate that a more severe or active PsA disease that requires antirheumatic treatment during pregnancy, especially bDMARDs, is associated with increased risks of adverse pregnancy outcomes compared to non-PsA pregnancies,” Dr. Remaeus and colleagues write in their study. “The risk of preterm birth in PsA pregnancies is further influenced by parity with the most increased risks observed in first pregnancies.”
In a nationwide, register-based cohort study, the researchers evaluated 921 pregnancies of women with PsA between 2007 and 2017, comparing them to the pregnancies of 9,210 women without PsA over the same time frame. The pregnancies for women with PsA were further categorized based on whether the women had not received antirheumatic treatment in the year prior to and/or during pregnancy (495 pregnancies) or had received antirheumatic treatment at any point in the year before and/or during pregnancy (426 pregnancies).
Of the women in the PsA group who were treated in the year prior to pregnancy (170 women), 39.4% received monotherapy with a conventional synthetic DMARD (csDMARD) such as an antimalarial, methotrexate, or sulfasalazine; 24.1% received oral corticosteroids, and 15.9% received a tumor necrosis factor inhibitor (TNFi), whereas about 20% of women received two or more antirheumatic drugs.
In the group of women treated during pregnancy (256 women), 153 did not receive bDMARDs; of these, 41.8% had monotherapy with either a csDMARD or corticosteroids, whereas the group treated with bDMARDs received TNFi monotherapy (43.7%) or TNFi with corticosteroids (35.9%), TNFi with csDMARD (9.7%), or TNFi with csDMARD plus corticosteroids (9.7%).
A majority of women in both groups (70.1%) were between ages 30 and 34 years (37.1%) or older than age 35 years (33%) and had delivered more than one child (63.2%). Women in the PsA group were more likely to be born in a Nordic country (91.8% vs. 82.8%), to have a body mass index between 30.0 and 60.0 kg/m2 (19.9% vs. 12.6%), to be a smoker (9.2% vs. 5.3%), to have hypertension (1.4% vs. 0.8%) or diabetes (1.3% vs. 0.5%) prior to pregnancy, and to have a higher level of education (>12 years; 50.1% vs. 43.3%), compared with women in the non-PsA group.
The results showed women in the PsA group were more likely to experience preterm birth (adjusted odds ratio, 1.69; 95% confidence interval, 1.27-2.24) and undergo an elective (aOR, 1.77; 95% CI, 1.43-2.20) or emergency C-section (aOR, 1.42; 95% CI, 1.10-1.84). The group at highest risk for preterm birth with regard to parity was women with PsA having their first child (aOR, 3.95; 95% CI, 1.43-10.95).
Women who received antirheumatic treatment were at greater risk for experiencing preterm birth (aOR, 2.30; 95% CI, 1.49-3.56), and this risk was even higher for treatment with bDMARDs, compared with women without PsA (aOR, 4.49; 95% CI, 2.60-7.79). Use of bDMARDs also was associated with higher risks for spontaneous preterm birth (aOR, 4.73; 95% CI, 2.53-8.87), preterm birth between 32 and 36 weeks’ gestation (aOR, 5.06; 95% CI, 2.91-8.79), elective C-section (aOR, 2.72; 95% CI, 1.61-4.59), emergency C-section (aOR, 2.06; 95% CI, 1.04-4.07), and preeclampsia (aOR, 2.88, 95% CI, 1.35-6.17).
The researchers note that women with PsA should be evaluated for preterm birth particularly if they are having their first child, and “from a clinical point of view, all women with PsA, regardless of antirheumatic treatment, should be counseled about pregnancy outcomes and receive individualized monitoring during pregnancy.”
Are adverse outcomes linked to disease activity or treatment?
Patients in the study had a higher risk of adverse outcomes when they had a PsA diagnosis, and when they received antirheumatic treatment – but were the adverse outcomes associated with a patient’s high disease activity or need for antirheumatic treatment?
“Our interpretation is that a PsA disease that requires continued antirheumatic treatment during pregnancy is more severe than PsA that does not require treatment,” Dr. Remaeus and colleagues write. “Thus, the increased risk of adverse outcomes in pregnancies with maternal antirheumatic treatment is probably attributed to disease severity rather than an effect of the medication itself.”
Anja Strangfeld, MD, PhD, of the German Rheumatism Research Centre in Berlin, told this news organization that the results of the study are important because it is one of the first to report differences in risk in pregnancy outcomes for women with and without PsA.
“The information is relevant to guide rheumatologists in advising patients with PsA when planning the first or subsequent pregnancies,” she said. “The results are reassuring in reporting that the elevated risk for PsA patients for adverse pregnancy outcomes is low in patients not in need of antirheumatic medication, presumably in low-disease activity.”
However, the study is still unclear on whether the association with adverse pregnancy outcomes in patients is the result of higher disease activity or the need for antirheumatic treatment, she explained.
“It was only hypothesized that those patients under bDMARD treatment are/were in high disease activity. There [is] no information on disease activity in the data sources, which limits the results,” she said. “The investigation still does not solve the important question – if adverse pregnancy outcomes are rather related to high disease activity or the medication to treat this situation.”
There was no specific funding for this study. The study authors and Dr. Strangfeld have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Hot temperatures in outdoor lockboxes increase sample errors
, according to results from a recent study published in the American Journal of Clinical Pathology.
“Our findings indicate that samples (centrifuged or not centrifuged) were impacted by extreme summer temperatures when stored for short periods of time inside commonly used steel lockboxes,” Joseph R. Wiencek, PhD, medical director of clinical chemistry, Vanderbilt University School of Medicine Core Laboratory in Nashville, said in an interview.
Dr. Wiencek and colleagues picked two dates during the summer of 2019 in a mid-Atlantic state to place two courier lockboxes (LabLocker-KF300) outside in hot temperatures (32º C) starting at 11 a.m., with one lockbox containing two 24-oz cold packs (Nordic NI24) and the other containing no cold packs. The researchers monitored the temperatures of each lockbox over the course of 4 hours.
Overall, eight participants had seven samples in lithium heparin drawn for two studies evaluating centrifuged or not centrifuged samples. In the first study, four participants had seven samples drawn, with one centrifuged sample serving as a control for each patient. The other six samples were wrapped in paper towels, placed in resealable plastic bags, and distributed evenly in the warm and cold lockboxes. The samples did not directly touch the cold packs in the cold lockbox. At 1 hour, 2 hours, and 4 hours, a participant’s sample was removed from each lockbox and centrifuged.
In the second study, another four participants had seven samples drawn. As in the first study, all samples were centrifuged and placed in the lockboxes. For both studies, when samples were centrifuged, plasma from samples was left on the gel barrier when analyzed for concentrations of C-reactive protein, a comprehensive metabolic panel, lactate dehydrogenase (LDH), a lipid panel, magnesium, and phosphorus (Abbott Architect c16000).
In the study of uncentrifuged samples, Dr. Wiencek and colleagues found that when the temperature outside ranged from 28.2º to 44.0º C (mean 40.4º C), the temperature of the cold lockbox was between 16.5º to 22.3º C (mean 22.3º C). The temperature ranged between 34.4º to 46.9º C (mean 42.6º C) in the warm lockbox. For centrifuged samples, the cold lockbox temperature was between 12.2º to 23.0º C (mean 18.0º C) and the warm lockbox was between 25. to 40.8º C (mean 35.2º C) when the outdoor temperature ranged from 27.2º to 46.3º C (mean 37.9º C).
The researchers also calculated the significant change limit (SCL) for each analyte in each sample, finding that aspartate aminotransferase, glucose, LDH, and potassium significantly exceeded the SCL in both the centrifuged and uncentrifuged samples, with the greatest changes seen at the 4-hour timepoint for samples in the warm lockbox (P < .05 for all).
Lockbox instructions are “consistently inconsistent”
In viewing instructions for lockboxes across institutions, Dr. Wiencek said the “outdoor courier lockbox instructions among private, academic and reference laboratories were consistently inconsistent.” For example, no laboratories cited time restrictions for samples in lockboxes, and their descriptions on the number of cold packs a laboratory should use and where the lockbox should be placed varied. The inconsistencies “highlighted the emergent need for standardization and guidance documents for institutions to implement,” Dr. Wiencek said.
One unanswered question is how widespread the problem is. It is unclear how many outdoor courier lockboxes are currently in use in the United States or globally; however, experts agreed it was a common occurrence, with some of the largest laboratory service providers offering outdoor courier lockboxes to their clients.
“Courier lockboxes are everywhere. All you need to do is walk around your clinics that are at your hospitals or clinics located around your grocery store to find them,” Dr. Wiencek said. “Some hang on doors, while others can be found on the ground in direct sunlight on a hot summer day.”
What’s more, institutions may not realize how leaving samples outdoors for extended periods can affect results. “Care teams are commonly unaware that samples placed in these poorly designed lockboxes can experience extreme summer or winter temperatures that may lead to incorrect results,” Dr. Wiencek said. “Healthcare providers need to understand the hidden dangers courier lockboxes have on the quality of their patient’s test results.”
Amy L. Pyle-Eilola, PhD, clinical chemistry director at Nationwide Children’s Hospital in Columbus, Ohio, said a major strength of the study by Dr. Wiencek and colleagues “is just that it was done at all.”
“I appreciate the real-world nature of this study and that it provides a snapshot of what conditions are really like in a lockbox in the summer,” she said in an interview.
In the clinical lab, receiving samples that had been sitting in a courier lockbox “is not uncommon,” Dr. Pyle-Eilola said.
“When I have encountered these situations, I have struggled to decide if it is still appropriate to run the tests. I always look to the medical literature for assistance with these situations, but there has been a paucity of information available on the impact of lockbox storage,” she explained.
The study by Dr. Wiencek and colleagues “provides some much-needed evidence for what is acceptable for lockbox storage conditions,” she said.
Areas of future research
Rodney E. Rohde, PhD, university distinguished chair and professor of the Clinical Laboratory Science (CLS) Program at Texas State University in San Marcos, said in an interview that the study “does a nice job of looking at multiple analytes and controlling for several variables,” but the sample size is small and the results may be difficult to generalize.
Dr. Pyle-Eilola highlighted another limitation — “a common shortcoming of these kinds of studies” — in the use of healthy donors for patient samples, which narrows the range of assay results.
“It is possible that more significant variation in results may be observed in additional analytes if the samples had higher concentrations of those analytes,” she said. “Moreover, this is clinically relevant as the samples stored in such lockboxes are not always from healthy individuals and have abnormal concentrations of analytes.”
Mario Plebani, MD, professor of clinical biochemistry and clinical molecular biology and chief of the department of laboratory medicine at University Hospital of Padova in Padova, Italy, agreed with that assessment.
“[T]he risks for errors and patient safety are higher for values near to the upper or lower reference value, and in general for samples collected in patients with particular diseases and clinical conditions,” he said in an interview.
“This paper deserves a commenting editorial to better highlight the urgent need for further studies on the same issue and in general on the risk in the pre-pre-analytical phase, including sample storage and transportation,” he noted.
Another area of future research is studying patient samples exposed to hotter or colder temperatures in outdoor courier lockboxes outside the mid-Atlantic area. “Here in Texas, temperatures can reach extreme heat levels,” Dr. Rohde said, who added that use of outdoor lockboxes is “very common in my region.”
Dr. Wiencek disclosed he has been a consultant on this research topic for Roche Diagnostics and received an honorarium for speaking on the subject from the American Association for Clinical Chemistry and American Society of Clinical Pathology. The other authors have no relevant conflict of interest. Dr. Pyle-Eilola, Dr. Rohde, and Dr. Plebani have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, according to results from a recent study published in the American Journal of Clinical Pathology.
“Our findings indicate that samples (centrifuged or not centrifuged) were impacted by extreme summer temperatures when stored for short periods of time inside commonly used steel lockboxes,” Joseph R. Wiencek, PhD, medical director of clinical chemistry, Vanderbilt University School of Medicine Core Laboratory in Nashville, said in an interview.
Dr. Wiencek and colleagues picked two dates during the summer of 2019 in a mid-Atlantic state to place two courier lockboxes (LabLocker-KF300) outside in hot temperatures (32º C) starting at 11 a.m., with one lockbox containing two 24-oz cold packs (Nordic NI24) and the other containing no cold packs. The researchers monitored the temperatures of each lockbox over the course of 4 hours.
Overall, eight participants had seven samples in lithium heparin drawn for two studies evaluating centrifuged or not centrifuged samples. In the first study, four participants had seven samples drawn, with one centrifuged sample serving as a control for each patient. The other six samples were wrapped in paper towels, placed in resealable plastic bags, and distributed evenly in the warm and cold lockboxes. The samples did not directly touch the cold packs in the cold lockbox. At 1 hour, 2 hours, and 4 hours, a participant’s sample was removed from each lockbox and centrifuged.
In the second study, another four participants had seven samples drawn. As in the first study, all samples were centrifuged and placed in the lockboxes. For both studies, when samples were centrifuged, plasma from samples was left on the gel barrier when analyzed for concentrations of C-reactive protein, a comprehensive metabolic panel, lactate dehydrogenase (LDH), a lipid panel, magnesium, and phosphorus (Abbott Architect c16000).
In the study of uncentrifuged samples, Dr. Wiencek and colleagues found that when the temperature outside ranged from 28.2º to 44.0º C (mean 40.4º C), the temperature of the cold lockbox was between 16.5º to 22.3º C (mean 22.3º C). The temperature ranged between 34.4º to 46.9º C (mean 42.6º C) in the warm lockbox. For centrifuged samples, the cold lockbox temperature was between 12.2º to 23.0º C (mean 18.0º C) and the warm lockbox was between 25. to 40.8º C (mean 35.2º C) when the outdoor temperature ranged from 27.2º to 46.3º C (mean 37.9º C).
The researchers also calculated the significant change limit (SCL) for each analyte in each sample, finding that aspartate aminotransferase, glucose, LDH, and potassium significantly exceeded the SCL in both the centrifuged and uncentrifuged samples, with the greatest changes seen at the 4-hour timepoint for samples in the warm lockbox (P < .05 for all).
Lockbox instructions are “consistently inconsistent”
In viewing instructions for lockboxes across institutions, Dr. Wiencek said the “outdoor courier lockbox instructions among private, academic and reference laboratories were consistently inconsistent.” For example, no laboratories cited time restrictions for samples in lockboxes, and their descriptions on the number of cold packs a laboratory should use and where the lockbox should be placed varied. The inconsistencies “highlighted the emergent need for standardization and guidance documents for institutions to implement,” Dr. Wiencek said.
One unanswered question is how widespread the problem is. It is unclear how many outdoor courier lockboxes are currently in use in the United States or globally; however, experts agreed it was a common occurrence, with some of the largest laboratory service providers offering outdoor courier lockboxes to their clients.
“Courier lockboxes are everywhere. All you need to do is walk around your clinics that are at your hospitals or clinics located around your grocery store to find them,” Dr. Wiencek said. “Some hang on doors, while others can be found on the ground in direct sunlight on a hot summer day.”
What’s more, institutions may not realize how leaving samples outdoors for extended periods can affect results. “Care teams are commonly unaware that samples placed in these poorly designed lockboxes can experience extreme summer or winter temperatures that may lead to incorrect results,” Dr. Wiencek said. “Healthcare providers need to understand the hidden dangers courier lockboxes have on the quality of their patient’s test results.”
Amy L. Pyle-Eilola, PhD, clinical chemistry director at Nationwide Children’s Hospital in Columbus, Ohio, said a major strength of the study by Dr. Wiencek and colleagues “is just that it was done at all.”
“I appreciate the real-world nature of this study and that it provides a snapshot of what conditions are really like in a lockbox in the summer,” she said in an interview.
In the clinical lab, receiving samples that had been sitting in a courier lockbox “is not uncommon,” Dr. Pyle-Eilola said.
“When I have encountered these situations, I have struggled to decide if it is still appropriate to run the tests. I always look to the medical literature for assistance with these situations, but there has been a paucity of information available on the impact of lockbox storage,” she explained.
The study by Dr. Wiencek and colleagues “provides some much-needed evidence for what is acceptable for lockbox storage conditions,” she said.
Areas of future research
Rodney E. Rohde, PhD, university distinguished chair and professor of the Clinical Laboratory Science (CLS) Program at Texas State University in San Marcos, said in an interview that the study “does a nice job of looking at multiple analytes and controlling for several variables,” but the sample size is small and the results may be difficult to generalize.
Dr. Pyle-Eilola highlighted another limitation — “a common shortcoming of these kinds of studies” — in the use of healthy donors for patient samples, which narrows the range of assay results.
“It is possible that more significant variation in results may be observed in additional analytes if the samples had higher concentrations of those analytes,” she said. “Moreover, this is clinically relevant as the samples stored in such lockboxes are not always from healthy individuals and have abnormal concentrations of analytes.”
Mario Plebani, MD, professor of clinical biochemistry and clinical molecular biology and chief of the department of laboratory medicine at University Hospital of Padova in Padova, Italy, agreed with that assessment.
“[T]he risks for errors and patient safety are higher for values near to the upper or lower reference value, and in general for samples collected in patients with particular diseases and clinical conditions,” he said in an interview.
“This paper deserves a commenting editorial to better highlight the urgent need for further studies on the same issue and in general on the risk in the pre-pre-analytical phase, including sample storage and transportation,” he noted.
Another area of future research is studying patient samples exposed to hotter or colder temperatures in outdoor courier lockboxes outside the mid-Atlantic area. “Here in Texas, temperatures can reach extreme heat levels,” Dr. Rohde said, who added that use of outdoor lockboxes is “very common in my region.”
Dr. Wiencek disclosed he has been a consultant on this research topic for Roche Diagnostics and received an honorarium for speaking on the subject from the American Association for Clinical Chemistry and American Society of Clinical Pathology. The other authors have no relevant conflict of interest. Dr. Pyle-Eilola, Dr. Rohde, and Dr. Plebani have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, according to results from a recent study published in the American Journal of Clinical Pathology.
“Our findings indicate that samples (centrifuged or not centrifuged) were impacted by extreme summer temperatures when stored for short periods of time inside commonly used steel lockboxes,” Joseph R. Wiencek, PhD, medical director of clinical chemistry, Vanderbilt University School of Medicine Core Laboratory in Nashville, said in an interview.
Dr. Wiencek and colleagues picked two dates during the summer of 2019 in a mid-Atlantic state to place two courier lockboxes (LabLocker-KF300) outside in hot temperatures (32º C) starting at 11 a.m., with one lockbox containing two 24-oz cold packs (Nordic NI24) and the other containing no cold packs. The researchers monitored the temperatures of each lockbox over the course of 4 hours.
Overall, eight participants had seven samples in lithium heparin drawn for two studies evaluating centrifuged or not centrifuged samples. In the first study, four participants had seven samples drawn, with one centrifuged sample serving as a control for each patient. The other six samples were wrapped in paper towels, placed in resealable plastic bags, and distributed evenly in the warm and cold lockboxes. The samples did not directly touch the cold packs in the cold lockbox. At 1 hour, 2 hours, and 4 hours, a participant’s sample was removed from each lockbox and centrifuged.
In the second study, another four participants had seven samples drawn. As in the first study, all samples were centrifuged and placed in the lockboxes. For both studies, when samples were centrifuged, plasma from samples was left on the gel barrier when analyzed for concentrations of C-reactive protein, a comprehensive metabolic panel, lactate dehydrogenase (LDH), a lipid panel, magnesium, and phosphorus (Abbott Architect c16000).
In the study of uncentrifuged samples, Dr. Wiencek and colleagues found that when the temperature outside ranged from 28.2º to 44.0º C (mean 40.4º C), the temperature of the cold lockbox was between 16.5º to 22.3º C (mean 22.3º C). The temperature ranged between 34.4º to 46.9º C (mean 42.6º C) in the warm lockbox. For centrifuged samples, the cold lockbox temperature was between 12.2º to 23.0º C (mean 18.0º C) and the warm lockbox was between 25. to 40.8º C (mean 35.2º C) when the outdoor temperature ranged from 27.2º to 46.3º C (mean 37.9º C).
The researchers also calculated the significant change limit (SCL) for each analyte in each sample, finding that aspartate aminotransferase, glucose, LDH, and potassium significantly exceeded the SCL in both the centrifuged and uncentrifuged samples, with the greatest changes seen at the 4-hour timepoint for samples in the warm lockbox (P < .05 for all).
Lockbox instructions are “consistently inconsistent”
In viewing instructions for lockboxes across institutions, Dr. Wiencek said the “outdoor courier lockbox instructions among private, academic and reference laboratories were consistently inconsistent.” For example, no laboratories cited time restrictions for samples in lockboxes, and their descriptions on the number of cold packs a laboratory should use and where the lockbox should be placed varied. The inconsistencies “highlighted the emergent need for standardization and guidance documents for institutions to implement,” Dr. Wiencek said.
One unanswered question is how widespread the problem is. It is unclear how many outdoor courier lockboxes are currently in use in the United States or globally; however, experts agreed it was a common occurrence, with some of the largest laboratory service providers offering outdoor courier lockboxes to their clients.
“Courier lockboxes are everywhere. All you need to do is walk around your clinics that are at your hospitals or clinics located around your grocery store to find them,” Dr. Wiencek said. “Some hang on doors, while others can be found on the ground in direct sunlight on a hot summer day.”
What’s more, institutions may not realize how leaving samples outdoors for extended periods can affect results. “Care teams are commonly unaware that samples placed in these poorly designed lockboxes can experience extreme summer or winter temperatures that may lead to incorrect results,” Dr. Wiencek said. “Healthcare providers need to understand the hidden dangers courier lockboxes have on the quality of their patient’s test results.”
Amy L. Pyle-Eilola, PhD, clinical chemistry director at Nationwide Children’s Hospital in Columbus, Ohio, said a major strength of the study by Dr. Wiencek and colleagues “is just that it was done at all.”
“I appreciate the real-world nature of this study and that it provides a snapshot of what conditions are really like in a lockbox in the summer,” she said in an interview.
In the clinical lab, receiving samples that had been sitting in a courier lockbox “is not uncommon,” Dr. Pyle-Eilola said.
“When I have encountered these situations, I have struggled to decide if it is still appropriate to run the tests. I always look to the medical literature for assistance with these situations, but there has been a paucity of information available on the impact of lockbox storage,” she explained.
The study by Dr. Wiencek and colleagues “provides some much-needed evidence for what is acceptable for lockbox storage conditions,” she said.
Areas of future research
Rodney E. Rohde, PhD, university distinguished chair and professor of the Clinical Laboratory Science (CLS) Program at Texas State University in San Marcos, said in an interview that the study “does a nice job of looking at multiple analytes and controlling for several variables,” but the sample size is small and the results may be difficult to generalize.
Dr. Pyle-Eilola highlighted another limitation — “a common shortcoming of these kinds of studies” — in the use of healthy donors for patient samples, which narrows the range of assay results.
“It is possible that more significant variation in results may be observed in additional analytes if the samples had higher concentrations of those analytes,” she said. “Moreover, this is clinically relevant as the samples stored in such lockboxes are not always from healthy individuals and have abnormal concentrations of analytes.”
Mario Plebani, MD, professor of clinical biochemistry and clinical molecular biology and chief of the department of laboratory medicine at University Hospital of Padova in Padova, Italy, agreed with that assessment.
“[T]he risks for errors and patient safety are higher for values near to the upper or lower reference value, and in general for samples collected in patients with particular diseases and clinical conditions,” he said in an interview.
“This paper deserves a commenting editorial to better highlight the urgent need for further studies on the same issue and in general on the risk in the pre-pre-analytical phase, including sample storage and transportation,” he noted.
Another area of future research is studying patient samples exposed to hotter or colder temperatures in outdoor courier lockboxes outside the mid-Atlantic area. “Here in Texas, temperatures can reach extreme heat levels,” Dr. Rohde said, who added that use of outdoor lockboxes is “very common in my region.”
Dr. Wiencek disclosed he has been a consultant on this research topic for Roche Diagnostics and received an honorarium for speaking on the subject from the American Association for Clinical Chemistry and American Society of Clinical Pathology. The other authors have no relevant conflict of interest. Dr. Pyle-Eilola, Dr. Rohde, and Dr. Plebani have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
How an ‘ad hoc’ hospitalist model evolved during India’s COVID surge
Hospital administrators recognize the efficiencies
A year after the start of the COVID-19 pandemic, as the United States was getting a reprieve in new cases from its winter surge, the opposite was happening in the rest of the world. In India, a deadly second wave hit, crippling the health care system in the country for months.
Yugandhar Bhatt, MBBS, MD, a consultant pulmonologist with Yashoda Hospital–Malakpet in Hyderabad, India, told this news organization that someone looking at his hospital before the pandemic – a 400-bed multispecialty care unit – would see patients being treated for respiratory failure secondary to exacerbation of chronic obstructive pulmonary disease, bronchial asthma, community-acquired pneumonia, and heart failure. About 30-40 patients per day were treated on an outpatient basis, and more than 30 people were admitted as inpatients.
“After [the] COVID-19 surge, our hospital totally divided into COVID and non-COVID [wards], in which COVID patients occupied 70% of [the] total,” he said. About half of COVID-19 patients were in the ICU, with half of those patients requiring supplemental oxygen.
During the first wave in India, which lasted from May to December 2020, 50% of patients who were intubated were discharged. The percentage of extubated patients decreased to 20% in the second wave, Dr. Bhatt said.
The death toll during the second wave of COVID-19 cases was unlike anything India has seen previously. Between March 1 and June 29, 2021, an estimated 19.24 million individuals were newly infected with COVID-19 and 241,206 patients died, according to Our World in Data, a project of the Global Change Data Lab. When the second wave peaked on May 22, more than 4,000 people were dying each day.
“All hospitals [in India] were treating COVID-19 more than any other acute or chronic disease,” Ramesh Adhikari, MD, MS, SFHM, a hospitalist with Franciscan Health in Lafayette, Ind., said in an interview.
Challenges arose in treating COVID-19 in India that ran counter to how medicine was usually performed. Physicians were seeing more inpatient cases than usual – and more patients in general. The change, Dr. Adhikari said, forced health care providers to think outside the box.
An ‘on-the-fly’ hospitalist model
Patients in India access health care by visiting a hospital or primary health center and then are referred out to consultants – specialist doctors – if needed. While India has universal health coverage, it is a multi-payer system that includes approximately 37% of the population covered under the government plan, a large number of private health care facilities and no caps on cost-sharing for the patient. Initiatives like Rashtriya Swasthya Bima Yojana in 2008 and Ayushman Bharat-Pradhan Mantri Jan Arogya Yojana in 2018 have attempted to close the gap and raise the number of lower-income individuals in India covered under the government plan and reduce out-of-pocket spending. Out-of-pocket payments still consist of about 70% of total health expenditures, according to the Commonwealth Fund.
“There is not much scope for a hospitalist because it’s so cash driven,” Shyam Odeti, MD, SFHM, section chief, hospital medicine, at the Carilion Clinic in Roanoke, Va., said in an interview. “For a hospitalist, there is no urgency in getting them out of the hospital. There was no need for much efficiency before.”
The first issue during the second wave was figuring out which consultants would care for COVID-19 patients. As there is no dedicated specialty for infectious disease in India, the responsibilities fell to internists and critical care medicine consultants who volunteered. Both are considered small specialties in India. They became “makeshift hospitalists” who learned as they went and became the experts in COVID-19 care, treating their own patients while making themselves available for consultations, Dr. Odeti said.
While no official hospital medicine model in India exists like in the United States, the second COVID-19 surge caused these consultants to begin thinking like hospitalists. Tenets of hospital medicine – like team-based treatment across specialties – arose out of necessity during the crisis. “They were trying to implement a hospitalist model because that’s the only way they could treat COVID-19,” said Dr. Adhikari, an editorial advisory board member for the Hospitalist.
“Even in the U.S. when we started the hospitalist model, it started out of necessity. It’s a combination of creating efficiencies and improving quality,” Dr. Odeti said. “It’s the same thing in India. It’s borne of necessity, but it was [done] at a rapid pace.”
Problems with patient flow
The next issue was triaging patients in the hospital based on COVID-19 severity. When the second wave began, hospitals in India ran out of beds and experienced staff shortages like in many countries. But this situation “was unusual for the health system,” according to Dr. Odeti, who is also an editorial board member for the Hospitalist.
“We never had that issue. There were so many patients wanting to come to the hospital, and so there was this rush.” There was no process to triage patients to determine who needed to stay. “Everybody got put into the hospital,” he said.
Once it was determined who would take care of patients with COVID-19, access to supplies became the primary problem, Dr. Adhikari explained. Lack of oxygen, ventilators, and critical medicines like the antiviral drug remdesivir were and continue to be in short supply. “I had friends who [said] they could not admit patients because they were worried if their oxygen supply [went] low in the middle of the night. They will treat the patients who were already admitted versus taking new patients. That had caused problems for the administrators,” Dr. Adhikari added.
It is also a source of additional stress for the physicians. Where patients flow through a hospital medicine model in the United States, a system that might include case managers, social workers, pharmacists, physician advocates, and other professionals to keep a patient’s care on track, the physician is the go-to person in India for patient care. While physicians provide access to medications and remain available to a patient’s family, those duties become much harder when caring for a greater number of patients during the pandemic. “That has led to some unrealistic expectations among the patients,” Dr. Adhikari said.
Dr. Bhatt said “more than half” of a physician’s time in India is spent counseling patients on concerns about COVID-19. “Awareness about the disease is limited from the patient and patient’s family perspective, as [there is] too much apprehension toward the nature of [the] disease,” he added. “Theoretical discussions collected from social media” obstruct the physician from executing his or her duties.
Physicians in India have had to contend with physical violence from patients and individuals on the street, Dr. Adhikari added. Workplace violence was already a concern – for years, the Indian Medical Association has cited a statistic that 75% of doctors in India have experienced violence at work (Indian J Psychiatry. 2019 Apr;61[Suppl 4]:S782-5). But the threat of violence against physicians has sharply increased during the COVID-19 pandemic. Disruptions to daily life through lockdowns “made people fearful, anxious, and sometimes they have found it difficult to access emergency treatment,” according to a letter published by Karthikeyan Iyengar and colleagues in the Postgraduate Medical Journal. In response to the restlessness, irritation, and despair resulting from hospitals closing their doors, “people have shown their frustration by verbally abusing and threatening to physically assault doctors and other health care workers,” the authors wrote.
A telemedicine boon in India
Back in the United States, hospitalists with family and friends in India were trying to figure out how to help. Some were working through the day, only to answer calls and WhatsApp messages from loved ones at night. “Everyone knows a physician or someone who’s your colleague, who owns a hospital or runs a hospital, or one of the family members is sick,” Dr. Adhikari said.
These U.S.-based hospitalists were burning the candle at both ends, helping with the pandemic in both countries. Physicians in India were posing questions to U.S. colleagues who they saw as having the most recent evidence for COVID-19 treatment. Out of the 180 physicians he trained with in India, Dr. Odeti said 110 of the physicians were in a large WhatsApp group chat that was constantly exchanging messages and serving as “kind of a friendly support group.”
In Dr. Odeti’s group chat, physicians helped one another find hospital beds for patients who reached out to them. “The first couple of weeks, there was no proper way for people to know where [patients] were based. There was no way to find if this hospital had a bed, so they reached out to any doctors they knew,” he said.
While he said it was emotionally draining, “at the same time, we felt a responsibility toward colleagues in India,” Dr. Odeti said, noting that as COVID-19 cases have decreased in India, the requests have been less frequent.
Because of concerns about traveling to India during the pandemic while on a J-1, H-1B, or other visa with the United States, directly helping friends and family in India seemed out of reach. But many hospitalists of Indian origin instead turned to telemedicine to help their colleagues. Telemedicine had already been steadily growing in India, but was accelerated by the pandemic. The current ratio of doctors to patients in India is 0.62 to 1,000 – lower than recommendations from the World Health Organization. That makes telemedicine a unique opportunity for one physician in India to reach many patients regardless of location.
Dr. Adhikari said he helped out his colleagues in India by performing consults for their patients. “They were just worried because they did not ‘know where to go, or what to get,” he said. “I was treating more patients in India than I was actually treating here.”
In March 2020, the Indian Ministry of Health and Family Welfare released telemedicine practice guidelines for the country, which relaxed regulations on privacy requirements and has been credited in part for giving telemedicine an additional boost during the pandemic. “That makes it easy for people to reach out but also has its own problems,” Dr. Adhikari said.
Monitoring of milder COVID-19 cases that don’t require hospitalization can be performed by a nurse who calls every few hours to check on a patient, make recommendations, and text treatment plans. “The telemedicine platforms are being adopted really fast,” Dr. Adhikari said. “The platforms were built in no time.”
According to NewZoo, a games market data analytics company, India has 345.9 million smartphone users as of 2019 – the second highest number of users in the world after China. Dr. Odeti said he believes telemedicine will be widely adopted.
“In India, they are very proactive in accepting these kinds of methods, so I’m sure they will,” he said. “Governments were trying to do it before the pandemic, because access to care is a problem in India. There are villages which are very, very remote.”
Reversion to old systems
After the peak in late May, new COVID-19 cases in India began to decrease, and the second wave waned on a national level. Hospitals began to get the supplies they needed, beds are available, and patients aren’t as sick as before, according to Dr. Adhikari. The federal government has begun issuing supplies to patients in each state, including COVID-19 vaccines. “The peak for the second wave is gone,” he said.
What remains is a group of physicians trained in how to triage patients and create efficiencies in a hospital setting. Could those skills be put to use elsewhere in India after the pandemic?
According to Dr. Bhatt, the patient care model is likely to revert to the system that existed before. “Whatever the changes, interims of bed occupancy, cost of ICU will be temporary [and] will change to normal,” he said. “But awareness about masks [and] sanitizing methods will be permanent.”
Dr. Adhikari believes that not utilizing the skills of newly minted hospitalists in India would be a missed opportunity. “This is a silver lining from COVID-19, that hospital medicine plays a vital role in the sickest patients, whether it is in India or the U.S. or anywhere,” he said. “I think the model of hospital medicine should be adopted. It’s not: ‘Should it really be adopted or not?’ It should be. There is a huge potential in doing inpatient coordinated [care], having people dedicated in the hospital.”
There are tangible benefits to creating efficiencies in India’s health system, Dr. Odeti said. Length of stay for sicker patients “was much longer” at 10-14 days during the second wave, compared with the United States, before lowering to around 5 days. “These hospitals right now are learning the efficient ways of doing it: when to send [patients] out, how to send them out, how to [perform] service-based practices, creating processes which were nonexistent before.”
While he doesn’t personally believe physicians will adopt a full-fledged hospitalist model unless the payer structure in India changes, “these people are at an advantage with this extra set of skills,” he said. “I think all the knowledge that these people have are going to come in handy.”
Opportunities for growth
Dr. Odeti sees the potential for the hospitalist model to grow in India – if not into its own specialty, then in how critical care consultants handle sicker patients and handoffs.
“The critical care clinician cannot keep the patient from the time they are admitted to the ICU until the discharge, so there will be a need for the transition,” Dr. Odeti said. “In the past, there were not many capabilities in Indian health systems to take care of these extremely sick patients, and now it is evolving. I think that is one more thing that will help.”
Dr. Adhikari said hospital systems in India are beginning to realize how having dedicated hospital physicians could benefit them. In India, “if you’re sick, you go to your doctor, you get treated and you disappear,” he said. The next time, you may see the same doctor or a completely different doctor. “There’s no system there, so it’s really hard for hospital medicine as such because patients, when they are very sick, they just come to the ER. They’re not followed by their primary care.”
Anecdotally, Dr. Odeti sees patients already adapting to having access to a physician for asking questions normally answered by primary care physicians. “I think primary care will come into play,” he said. “When I was doing a Zoom call for patients, they were asking me questions about sciatica. I think they are getting comfortable with this technology.”
A hospitalist model could even be applied to specific diseases with a large population of patients. Hospital administrators “have seen this for the first time, how efficient it could be if they had their own hospitalists and actually run it. So that’s the part that has crossed their minds,” Dr. Adhikari said. “How they will apply it going forward, other than during the COVID-19 pandemic, depends on the size of the hospital and the volume of the patients for a particular disease.”
“You can see in certain areas there is large growth for hospital medicine. But to rise to the level of the United States and how we do it, India needs bigger health systems to adopt the model,” Dr. Adhikari said.
Hospital administrators recognize the efficiencies
Hospital administrators recognize the efficiencies
A year after the start of the COVID-19 pandemic, as the United States was getting a reprieve in new cases from its winter surge, the opposite was happening in the rest of the world. In India, a deadly second wave hit, crippling the health care system in the country for months.
Yugandhar Bhatt, MBBS, MD, a consultant pulmonologist with Yashoda Hospital–Malakpet in Hyderabad, India, told this news organization that someone looking at his hospital before the pandemic – a 400-bed multispecialty care unit – would see patients being treated for respiratory failure secondary to exacerbation of chronic obstructive pulmonary disease, bronchial asthma, community-acquired pneumonia, and heart failure. About 30-40 patients per day were treated on an outpatient basis, and more than 30 people were admitted as inpatients.
“After [the] COVID-19 surge, our hospital totally divided into COVID and non-COVID [wards], in which COVID patients occupied 70% of [the] total,” he said. About half of COVID-19 patients were in the ICU, with half of those patients requiring supplemental oxygen.
During the first wave in India, which lasted from May to December 2020, 50% of patients who were intubated were discharged. The percentage of extubated patients decreased to 20% in the second wave, Dr. Bhatt said.
The death toll during the second wave of COVID-19 cases was unlike anything India has seen previously. Between March 1 and June 29, 2021, an estimated 19.24 million individuals were newly infected with COVID-19 and 241,206 patients died, according to Our World in Data, a project of the Global Change Data Lab. When the second wave peaked on May 22, more than 4,000 people were dying each day.
“All hospitals [in India] were treating COVID-19 more than any other acute or chronic disease,” Ramesh Adhikari, MD, MS, SFHM, a hospitalist with Franciscan Health in Lafayette, Ind., said in an interview.
Challenges arose in treating COVID-19 in India that ran counter to how medicine was usually performed. Physicians were seeing more inpatient cases than usual – and more patients in general. The change, Dr. Adhikari said, forced health care providers to think outside the box.
An ‘on-the-fly’ hospitalist model
Patients in India access health care by visiting a hospital or primary health center and then are referred out to consultants – specialist doctors – if needed. While India has universal health coverage, it is a multi-payer system that includes approximately 37% of the population covered under the government plan, a large number of private health care facilities and no caps on cost-sharing for the patient. Initiatives like Rashtriya Swasthya Bima Yojana in 2008 and Ayushman Bharat-Pradhan Mantri Jan Arogya Yojana in 2018 have attempted to close the gap and raise the number of lower-income individuals in India covered under the government plan and reduce out-of-pocket spending. Out-of-pocket payments still consist of about 70% of total health expenditures, according to the Commonwealth Fund.
“There is not much scope for a hospitalist because it’s so cash driven,” Shyam Odeti, MD, SFHM, section chief, hospital medicine, at the Carilion Clinic in Roanoke, Va., said in an interview. “For a hospitalist, there is no urgency in getting them out of the hospital. There was no need for much efficiency before.”
The first issue during the second wave was figuring out which consultants would care for COVID-19 patients. As there is no dedicated specialty for infectious disease in India, the responsibilities fell to internists and critical care medicine consultants who volunteered. Both are considered small specialties in India. They became “makeshift hospitalists” who learned as they went and became the experts in COVID-19 care, treating their own patients while making themselves available for consultations, Dr. Odeti said.
While no official hospital medicine model in India exists like in the United States, the second COVID-19 surge caused these consultants to begin thinking like hospitalists. Tenets of hospital medicine – like team-based treatment across specialties – arose out of necessity during the crisis. “They were trying to implement a hospitalist model because that’s the only way they could treat COVID-19,” said Dr. Adhikari, an editorial advisory board member for the Hospitalist.
“Even in the U.S. when we started the hospitalist model, it started out of necessity. It’s a combination of creating efficiencies and improving quality,” Dr. Odeti said. “It’s the same thing in India. It’s borne of necessity, but it was [done] at a rapid pace.”
Problems with patient flow
The next issue was triaging patients in the hospital based on COVID-19 severity. When the second wave began, hospitals in India ran out of beds and experienced staff shortages like in many countries. But this situation “was unusual for the health system,” according to Dr. Odeti, who is also an editorial board member for the Hospitalist.
“We never had that issue. There were so many patients wanting to come to the hospital, and so there was this rush.” There was no process to triage patients to determine who needed to stay. “Everybody got put into the hospital,” he said.
Once it was determined who would take care of patients with COVID-19, access to supplies became the primary problem, Dr. Adhikari explained. Lack of oxygen, ventilators, and critical medicines like the antiviral drug remdesivir were and continue to be in short supply. “I had friends who [said] they could not admit patients because they were worried if their oxygen supply [went] low in the middle of the night. They will treat the patients who were already admitted versus taking new patients. That had caused problems for the administrators,” Dr. Adhikari added.
It is also a source of additional stress for the physicians. Where patients flow through a hospital medicine model in the United States, a system that might include case managers, social workers, pharmacists, physician advocates, and other professionals to keep a patient’s care on track, the physician is the go-to person in India for patient care. While physicians provide access to medications and remain available to a patient’s family, those duties become much harder when caring for a greater number of patients during the pandemic. “That has led to some unrealistic expectations among the patients,” Dr. Adhikari said.
Dr. Bhatt said “more than half” of a physician’s time in India is spent counseling patients on concerns about COVID-19. “Awareness about the disease is limited from the patient and patient’s family perspective, as [there is] too much apprehension toward the nature of [the] disease,” he added. “Theoretical discussions collected from social media” obstruct the physician from executing his or her duties.
Physicians in India have had to contend with physical violence from patients and individuals on the street, Dr. Adhikari added. Workplace violence was already a concern – for years, the Indian Medical Association has cited a statistic that 75% of doctors in India have experienced violence at work (Indian J Psychiatry. 2019 Apr;61[Suppl 4]:S782-5). But the threat of violence against physicians has sharply increased during the COVID-19 pandemic. Disruptions to daily life through lockdowns “made people fearful, anxious, and sometimes they have found it difficult to access emergency treatment,” according to a letter published by Karthikeyan Iyengar and colleagues in the Postgraduate Medical Journal. In response to the restlessness, irritation, and despair resulting from hospitals closing their doors, “people have shown their frustration by verbally abusing and threatening to physically assault doctors and other health care workers,” the authors wrote.
A telemedicine boon in India
Back in the United States, hospitalists with family and friends in India were trying to figure out how to help. Some were working through the day, only to answer calls and WhatsApp messages from loved ones at night. “Everyone knows a physician or someone who’s your colleague, who owns a hospital or runs a hospital, or one of the family members is sick,” Dr. Adhikari said.
These U.S.-based hospitalists were burning the candle at both ends, helping with the pandemic in both countries. Physicians in India were posing questions to U.S. colleagues who they saw as having the most recent evidence for COVID-19 treatment. Out of the 180 physicians he trained with in India, Dr. Odeti said 110 of the physicians were in a large WhatsApp group chat that was constantly exchanging messages and serving as “kind of a friendly support group.”
In Dr. Odeti’s group chat, physicians helped one another find hospital beds for patients who reached out to them. “The first couple of weeks, there was no proper way for people to know where [patients] were based. There was no way to find if this hospital had a bed, so they reached out to any doctors they knew,” he said.
While he said it was emotionally draining, “at the same time, we felt a responsibility toward colleagues in India,” Dr. Odeti said, noting that as COVID-19 cases have decreased in India, the requests have been less frequent.
Because of concerns about traveling to India during the pandemic while on a J-1, H-1B, or other visa with the United States, directly helping friends and family in India seemed out of reach. But many hospitalists of Indian origin instead turned to telemedicine to help their colleagues. Telemedicine had already been steadily growing in India, but was accelerated by the pandemic. The current ratio of doctors to patients in India is 0.62 to 1,000 – lower than recommendations from the World Health Organization. That makes telemedicine a unique opportunity for one physician in India to reach many patients regardless of location.
Dr. Adhikari said he helped out his colleagues in India by performing consults for their patients. “They were just worried because they did not ‘know where to go, or what to get,” he said. “I was treating more patients in India than I was actually treating here.”
In March 2020, the Indian Ministry of Health and Family Welfare released telemedicine practice guidelines for the country, which relaxed regulations on privacy requirements and has been credited in part for giving telemedicine an additional boost during the pandemic. “That makes it easy for people to reach out but also has its own problems,” Dr. Adhikari said.
Monitoring of milder COVID-19 cases that don’t require hospitalization can be performed by a nurse who calls every few hours to check on a patient, make recommendations, and text treatment plans. “The telemedicine platforms are being adopted really fast,” Dr. Adhikari said. “The platforms were built in no time.”
According to NewZoo, a games market data analytics company, India has 345.9 million smartphone users as of 2019 – the second highest number of users in the world after China. Dr. Odeti said he believes telemedicine will be widely adopted.
“In India, they are very proactive in accepting these kinds of methods, so I’m sure they will,” he said. “Governments were trying to do it before the pandemic, because access to care is a problem in India. There are villages which are very, very remote.”
Reversion to old systems
After the peak in late May, new COVID-19 cases in India began to decrease, and the second wave waned on a national level. Hospitals began to get the supplies they needed, beds are available, and patients aren’t as sick as before, according to Dr. Adhikari. The federal government has begun issuing supplies to patients in each state, including COVID-19 vaccines. “The peak for the second wave is gone,” he said.
What remains is a group of physicians trained in how to triage patients and create efficiencies in a hospital setting. Could those skills be put to use elsewhere in India after the pandemic?
According to Dr. Bhatt, the patient care model is likely to revert to the system that existed before. “Whatever the changes, interims of bed occupancy, cost of ICU will be temporary [and] will change to normal,” he said. “But awareness about masks [and] sanitizing methods will be permanent.”
Dr. Adhikari believes that not utilizing the skills of newly minted hospitalists in India would be a missed opportunity. “This is a silver lining from COVID-19, that hospital medicine plays a vital role in the sickest patients, whether it is in India or the U.S. or anywhere,” he said. “I think the model of hospital medicine should be adopted. It’s not: ‘Should it really be adopted or not?’ It should be. There is a huge potential in doing inpatient coordinated [care], having people dedicated in the hospital.”
There are tangible benefits to creating efficiencies in India’s health system, Dr. Odeti said. Length of stay for sicker patients “was much longer” at 10-14 days during the second wave, compared with the United States, before lowering to around 5 days. “These hospitals right now are learning the efficient ways of doing it: when to send [patients] out, how to send them out, how to [perform] service-based practices, creating processes which were nonexistent before.”
While he doesn’t personally believe physicians will adopt a full-fledged hospitalist model unless the payer structure in India changes, “these people are at an advantage with this extra set of skills,” he said. “I think all the knowledge that these people have are going to come in handy.”
Opportunities for growth
Dr. Odeti sees the potential for the hospitalist model to grow in India – if not into its own specialty, then in how critical care consultants handle sicker patients and handoffs.
“The critical care clinician cannot keep the patient from the time they are admitted to the ICU until the discharge, so there will be a need for the transition,” Dr. Odeti said. “In the past, there were not many capabilities in Indian health systems to take care of these extremely sick patients, and now it is evolving. I think that is one more thing that will help.”
Dr. Adhikari said hospital systems in India are beginning to realize how having dedicated hospital physicians could benefit them. In India, “if you’re sick, you go to your doctor, you get treated and you disappear,” he said. The next time, you may see the same doctor or a completely different doctor. “There’s no system there, so it’s really hard for hospital medicine as such because patients, when they are very sick, they just come to the ER. They’re not followed by their primary care.”
Anecdotally, Dr. Odeti sees patients already adapting to having access to a physician for asking questions normally answered by primary care physicians. “I think primary care will come into play,” he said. “When I was doing a Zoom call for patients, they were asking me questions about sciatica. I think they are getting comfortable with this technology.”
A hospitalist model could even be applied to specific diseases with a large population of patients. Hospital administrators “have seen this for the first time, how efficient it could be if they had their own hospitalists and actually run it. So that’s the part that has crossed their minds,” Dr. Adhikari said. “How they will apply it going forward, other than during the COVID-19 pandemic, depends on the size of the hospital and the volume of the patients for a particular disease.”
“You can see in certain areas there is large growth for hospital medicine. But to rise to the level of the United States and how we do it, India needs bigger health systems to adopt the model,” Dr. Adhikari said.
A year after the start of the COVID-19 pandemic, as the United States was getting a reprieve in new cases from its winter surge, the opposite was happening in the rest of the world. In India, a deadly second wave hit, crippling the health care system in the country for months.
Yugandhar Bhatt, MBBS, MD, a consultant pulmonologist with Yashoda Hospital–Malakpet in Hyderabad, India, told this news organization that someone looking at his hospital before the pandemic – a 400-bed multispecialty care unit – would see patients being treated for respiratory failure secondary to exacerbation of chronic obstructive pulmonary disease, bronchial asthma, community-acquired pneumonia, and heart failure. About 30-40 patients per day were treated on an outpatient basis, and more than 30 people were admitted as inpatients.
“After [the] COVID-19 surge, our hospital totally divided into COVID and non-COVID [wards], in which COVID patients occupied 70% of [the] total,” he said. About half of COVID-19 patients were in the ICU, with half of those patients requiring supplemental oxygen.
During the first wave in India, which lasted from May to December 2020, 50% of patients who were intubated were discharged. The percentage of extubated patients decreased to 20% in the second wave, Dr. Bhatt said.
The death toll during the second wave of COVID-19 cases was unlike anything India has seen previously. Between March 1 and June 29, 2021, an estimated 19.24 million individuals were newly infected with COVID-19 and 241,206 patients died, according to Our World in Data, a project of the Global Change Data Lab. When the second wave peaked on May 22, more than 4,000 people were dying each day.
“All hospitals [in India] were treating COVID-19 more than any other acute or chronic disease,” Ramesh Adhikari, MD, MS, SFHM, a hospitalist with Franciscan Health in Lafayette, Ind., said in an interview.
Challenges arose in treating COVID-19 in India that ran counter to how medicine was usually performed. Physicians were seeing more inpatient cases than usual – and more patients in general. The change, Dr. Adhikari said, forced health care providers to think outside the box.
An ‘on-the-fly’ hospitalist model
Patients in India access health care by visiting a hospital or primary health center and then are referred out to consultants – specialist doctors – if needed. While India has universal health coverage, it is a multi-payer system that includes approximately 37% of the population covered under the government plan, a large number of private health care facilities and no caps on cost-sharing for the patient. Initiatives like Rashtriya Swasthya Bima Yojana in 2008 and Ayushman Bharat-Pradhan Mantri Jan Arogya Yojana in 2018 have attempted to close the gap and raise the number of lower-income individuals in India covered under the government plan and reduce out-of-pocket spending. Out-of-pocket payments still consist of about 70% of total health expenditures, according to the Commonwealth Fund.
“There is not much scope for a hospitalist because it’s so cash driven,” Shyam Odeti, MD, SFHM, section chief, hospital medicine, at the Carilion Clinic in Roanoke, Va., said in an interview. “For a hospitalist, there is no urgency in getting them out of the hospital. There was no need for much efficiency before.”
The first issue during the second wave was figuring out which consultants would care for COVID-19 patients. As there is no dedicated specialty for infectious disease in India, the responsibilities fell to internists and critical care medicine consultants who volunteered. Both are considered small specialties in India. They became “makeshift hospitalists” who learned as they went and became the experts in COVID-19 care, treating their own patients while making themselves available for consultations, Dr. Odeti said.
While no official hospital medicine model in India exists like in the United States, the second COVID-19 surge caused these consultants to begin thinking like hospitalists. Tenets of hospital medicine – like team-based treatment across specialties – arose out of necessity during the crisis. “They were trying to implement a hospitalist model because that’s the only way they could treat COVID-19,” said Dr. Adhikari, an editorial advisory board member for the Hospitalist.
“Even in the U.S. when we started the hospitalist model, it started out of necessity. It’s a combination of creating efficiencies and improving quality,” Dr. Odeti said. “It’s the same thing in India. It’s borne of necessity, but it was [done] at a rapid pace.”
Problems with patient flow
The next issue was triaging patients in the hospital based on COVID-19 severity. When the second wave began, hospitals in India ran out of beds and experienced staff shortages like in many countries. But this situation “was unusual for the health system,” according to Dr. Odeti, who is also an editorial board member for the Hospitalist.
“We never had that issue. There were so many patients wanting to come to the hospital, and so there was this rush.” There was no process to triage patients to determine who needed to stay. “Everybody got put into the hospital,” he said.
Once it was determined who would take care of patients with COVID-19, access to supplies became the primary problem, Dr. Adhikari explained. Lack of oxygen, ventilators, and critical medicines like the antiviral drug remdesivir were and continue to be in short supply. “I had friends who [said] they could not admit patients because they were worried if their oxygen supply [went] low in the middle of the night. They will treat the patients who were already admitted versus taking new patients. That had caused problems for the administrators,” Dr. Adhikari added.
It is also a source of additional stress for the physicians. Where patients flow through a hospital medicine model in the United States, a system that might include case managers, social workers, pharmacists, physician advocates, and other professionals to keep a patient’s care on track, the physician is the go-to person in India for patient care. While physicians provide access to medications and remain available to a patient’s family, those duties become much harder when caring for a greater number of patients during the pandemic. “That has led to some unrealistic expectations among the patients,” Dr. Adhikari said.
Dr. Bhatt said “more than half” of a physician’s time in India is spent counseling patients on concerns about COVID-19. “Awareness about the disease is limited from the patient and patient’s family perspective, as [there is] too much apprehension toward the nature of [the] disease,” he added. “Theoretical discussions collected from social media” obstruct the physician from executing his or her duties.
Physicians in India have had to contend with physical violence from patients and individuals on the street, Dr. Adhikari added. Workplace violence was already a concern – for years, the Indian Medical Association has cited a statistic that 75% of doctors in India have experienced violence at work (Indian J Psychiatry. 2019 Apr;61[Suppl 4]:S782-5). But the threat of violence against physicians has sharply increased during the COVID-19 pandemic. Disruptions to daily life through lockdowns “made people fearful, anxious, and sometimes they have found it difficult to access emergency treatment,” according to a letter published by Karthikeyan Iyengar and colleagues in the Postgraduate Medical Journal. In response to the restlessness, irritation, and despair resulting from hospitals closing their doors, “people have shown their frustration by verbally abusing and threatening to physically assault doctors and other health care workers,” the authors wrote.
A telemedicine boon in India
Back in the United States, hospitalists with family and friends in India were trying to figure out how to help. Some were working through the day, only to answer calls and WhatsApp messages from loved ones at night. “Everyone knows a physician or someone who’s your colleague, who owns a hospital or runs a hospital, or one of the family members is sick,” Dr. Adhikari said.
These U.S.-based hospitalists were burning the candle at both ends, helping with the pandemic in both countries. Physicians in India were posing questions to U.S. colleagues who they saw as having the most recent evidence for COVID-19 treatment. Out of the 180 physicians he trained with in India, Dr. Odeti said 110 of the physicians were in a large WhatsApp group chat that was constantly exchanging messages and serving as “kind of a friendly support group.”
In Dr. Odeti’s group chat, physicians helped one another find hospital beds for patients who reached out to them. “The first couple of weeks, there was no proper way for people to know where [patients] were based. There was no way to find if this hospital had a bed, so they reached out to any doctors they knew,” he said.
While he said it was emotionally draining, “at the same time, we felt a responsibility toward colleagues in India,” Dr. Odeti said, noting that as COVID-19 cases have decreased in India, the requests have been less frequent.
Because of concerns about traveling to India during the pandemic while on a J-1, H-1B, or other visa with the United States, directly helping friends and family in India seemed out of reach. But many hospitalists of Indian origin instead turned to telemedicine to help their colleagues. Telemedicine had already been steadily growing in India, but was accelerated by the pandemic. The current ratio of doctors to patients in India is 0.62 to 1,000 – lower than recommendations from the World Health Organization. That makes telemedicine a unique opportunity for one physician in India to reach many patients regardless of location.
Dr. Adhikari said he helped out his colleagues in India by performing consults for their patients. “They were just worried because they did not ‘know where to go, or what to get,” he said. “I was treating more patients in India than I was actually treating here.”
In March 2020, the Indian Ministry of Health and Family Welfare released telemedicine practice guidelines for the country, which relaxed regulations on privacy requirements and has been credited in part for giving telemedicine an additional boost during the pandemic. “That makes it easy for people to reach out but also has its own problems,” Dr. Adhikari said.
Monitoring of milder COVID-19 cases that don’t require hospitalization can be performed by a nurse who calls every few hours to check on a patient, make recommendations, and text treatment plans. “The telemedicine platforms are being adopted really fast,” Dr. Adhikari said. “The platforms were built in no time.”
According to NewZoo, a games market data analytics company, India has 345.9 million smartphone users as of 2019 – the second highest number of users in the world after China. Dr. Odeti said he believes telemedicine will be widely adopted.
“In India, they are very proactive in accepting these kinds of methods, so I’m sure they will,” he said. “Governments were trying to do it before the pandemic, because access to care is a problem in India. There are villages which are very, very remote.”
Reversion to old systems
After the peak in late May, new COVID-19 cases in India began to decrease, and the second wave waned on a national level. Hospitals began to get the supplies they needed, beds are available, and patients aren’t as sick as before, according to Dr. Adhikari. The federal government has begun issuing supplies to patients in each state, including COVID-19 vaccines. “The peak for the second wave is gone,” he said.
What remains is a group of physicians trained in how to triage patients and create efficiencies in a hospital setting. Could those skills be put to use elsewhere in India after the pandemic?
According to Dr. Bhatt, the patient care model is likely to revert to the system that existed before. “Whatever the changes, interims of bed occupancy, cost of ICU will be temporary [and] will change to normal,” he said. “But awareness about masks [and] sanitizing methods will be permanent.”
Dr. Adhikari believes that not utilizing the skills of newly minted hospitalists in India would be a missed opportunity. “This is a silver lining from COVID-19, that hospital medicine plays a vital role in the sickest patients, whether it is in India or the U.S. or anywhere,” he said. “I think the model of hospital medicine should be adopted. It’s not: ‘Should it really be adopted or not?’ It should be. There is a huge potential in doing inpatient coordinated [care], having people dedicated in the hospital.”
There are tangible benefits to creating efficiencies in India’s health system, Dr. Odeti said. Length of stay for sicker patients “was much longer” at 10-14 days during the second wave, compared with the United States, before lowering to around 5 days. “These hospitals right now are learning the efficient ways of doing it: when to send [patients] out, how to send them out, how to [perform] service-based practices, creating processes which were nonexistent before.”
While he doesn’t personally believe physicians will adopt a full-fledged hospitalist model unless the payer structure in India changes, “these people are at an advantage with this extra set of skills,” he said. “I think all the knowledge that these people have are going to come in handy.”
Opportunities for growth
Dr. Odeti sees the potential for the hospitalist model to grow in India – if not into its own specialty, then in how critical care consultants handle sicker patients and handoffs.
“The critical care clinician cannot keep the patient from the time they are admitted to the ICU until the discharge, so there will be a need for the transition,” Dr. Odeti said. “In the past, there were not many capabilities in Indian health systems to take care of these extremely sick patients, and now it is evolving. I think that is one more thing that will help.”
Dr. Adhikari said hospital systems in India are beginning to realize how having dedicated hospital physicians could benefit them. In India, “if you’re sick, you go to your doctor, you get treated and you disappear,” he said. The next time, you may see the same doctor or a completely different doctor. “There’s no system there, so it’s really hard for hospital medicine as such because patients, when they are very sick, they just come to the ER. They’re not followed by their primary care.”
Anecdotally, Dr. Odeti sees patients already adapting to having access to a physician for asking questions normally answered by primary care physicians. “I think primary care will come into play,” he said. “When I was doing a Zoom call for patients, they were asking me questions about sciatica. I think they are getting comfortable with this technology.”
A hospitalist model could even be applied to specific diseases with a large population of patients. Hospital administrators “have seen this for the first time, how efficient it could be if they had their own hospitalists and actually run it. So that’s the part that has crossed their minds,” Dr. Adhikari said. “How they will apply it going forward, other than during the COVID-19 pandemic, depends on the size of the hospital and the volume of the patients for a particular disease.”
“You can see in certain areas there is large growth for hospital medicine. But to rise to the level of the United States and how we do it, India needs bigger health systems to adopt the model,” Dr. Adhikari said.
Microbiome: Gut dysbiosis linked to development of alopecia areata
presented at the annual meeting of the Society for Investigative Dermatology.
There have been reports of gut microbiome dysbiosis associated with autoimmune diseases such as rheumatoid arthritis, diabetes, and celiac disease. “It is now clear that these events not just shape the immune response in the gut, but also distant sites and immune-privileged organs,” Tanya Sezin, a doctor of natural science from the University of Lübeck (Germany) and Columbia University, New York, said in her presentation.
Whether the gut microbiome may also play a role as an environmental factor in alopecia areata, another T-cell–mediated autoimmune disease for which there are few available treatment options, is being evaluated at the Christiano Laboratory at Columbia University, Dr. Sezin noted. “Much of the difficulty underlying the lack of an effective treatment has been the incomplete understanding of the pathogenesis of AA.”
She also referred to several case reports describing hair growth in patients who received fecal microbiota transplantation (FMT), including a 20-year-old with alopecia universalis, who experienced hair growth after receiving FMT for Crohn’s disease.
Dr. Sezin and colleagues at the lab first performed a study in mice to test whether the gut microbiome was involved in the pathogenesis of AA. Mice given an antibiotic cocktail of ampicillin, neomycin, and vancomycin prior to or at the time of a skin graft taken from a mouse model of AA to induce AA were protected from hair loss, while mice given the antibiotic cocktail after skin grafting were not protected from hair loss.
“16S rRNA sequencing analysis of the gut microbiota revealed a significant shift in gut microbiome composition in animals treated with antibiotics and protected from hair loss, as reflected by significant changes in alpha and beta diversity,” Dr. Sezin explained. “In AA mice, we also observed differential abundance of families from the Bacteroidetes and Firmicutes phyla.” Specifically, Lactobacillus murinus and Muribaculum intestinale were overrepresented in mice with AA.
The investigators then performed 16S rRNA sequencing on 26 patients with AA, who stopped treatment for 30 days beforehand, and 9 participants who did not have AA as controls. “Though we did not observe difference in alpha and beta diversity, we see changes in the relative abundance of several families belonging to the Firmicutes phyla,” in patients with AA, Dr. Sezin said.
In another cohort of 30 patients with AA and 20 participants without AA, who stopped treatment before the study, Dr. Sezin and colleagues found “differences in the relative abundance of members of the Firmicutes and Bacteroides phyla,” including Bacteroides caccae, Prevotella copri, Syntrophomonas wolfei, Blautia wexlerae, and Eubacterium eligens, she said. “Consistent with our findings, there are previous reports in the literature showing gut dysbiosis in several other autoimmune diseases associated with differential regulation of some of the top species we have identified.”
Dr. Sezin said her group is recruiting patients for a clinical trial evaluating FMT in patients with AA. “We plan to study the association between changes in the gut microbiome and immune cell composition in AA patients undergoing FMT,” she said. “Additionally, functional studies in mice are also currently [being conducted] to further pinpoint the contribution of gut microbiome to the pathogenesis of AA.”
When asked during the discussion session if there was any relationship between the skin microbiome and AA, Dr. Sezin said there was no connection found in mice studies, which she and her colleagues are investigating further. “In the human samples, we are currently recruiting more patients and healthy controls to try to get a better understanding of whether we see differences in the skin microbiome,” she added.
Dr. Sezin explained that how the gut microbiota “is really remediated in alopecia areata” is not well understood. “We think that it is possible that we see intestinal permeability in the gut due to the gut dysbiosis that we see in alopecia areata patients, and this might lead to systemic distribution of bacteria, which might cross-react or present cross reactivity with the antigens” identified in AA, which is also being investigated, she said.
FMT not a ‘simple fix’ for AA
Leslie Castelo-Soccio, MD, PhD, a dermatologist at the Children’s Hospital of Philadelphia, who was not involved with the research, said in an interview that the findings presented by Dr. Sezin show how AA shares similarities with other autoimmune diseases. “It does highlight how important the gut microbiome is to human disease, and that differences in relative abundance of bacteria play one part as a trigger in a genetically susceptible person.”
However, while some autoimmune diseases have a big difference in alpha and beta diversity, for example, “this has not been seen in people with alopecia areata,” Dr. Castelo-Soccio pointed out. “The differences are more subtle in terms of amounts of certain bacteria,” she said, noting that, in this study, the biggest differences were seen in the studies of mice.
Dr. Castelo-Soccio also said there may be also be differences in the gut microbiome in children and adults. “The gut microbiome shifts in very early childhood from a very diverse microbiome to a more ‘adult microbiome’ around age 4, which is the age we see the first peak of many autoimmune diseases, including alopecia areata. I think microbiome work in humans needs to focus on this transition point.”
As for the clinical trial at Columbia that is evaluating FMT in patients with AA, Dr. Castelo-Soccio said she is excited. “There is much to learn about fecal transplant for all diseases and about the role of the gut microbiome and environment. Most of what we know for fecal transplant centers on its use for Clostridium difficile infections.”
Patients and their families have been asking about the potential for FMT in alopecia area, Dr. Castelo-Soccio said, but some believe it is a “simple fix” when the reality is much more complex.
“When I speak to patients and families about this, I explain that currently the ‘active ingredient’ in fecal transplants is not definitively established. In any one donor, the community of bacteria is highly variable and can be from batch to batch. While the short-term risks are relatively low – cramping, diarrhea, discomfort, mode of delivery – there are reports of transmission of infectious bacteria from donors like [Escherichia] coli, which have led to severe infections.”
Long-term safety and durability of effects are also unclear, “so we do not know if a patient receiving one [FMT] will need many in the future. We do not know how changing the microbiome could affect the transplant recipient in terms of noninfectious diseases/disorders. We are learning about the role of microbiome in obesity, insulin resistance, mood disorders. We could be ‘fixing’ one trigger of alopecia but setting up [the] patient for other noninfectious conditions,” Dr. Castelo-Soccio said.
Dr. Sezin and Dr. Castelo-Soccio reported no relevant financial disclosures.
presented at the annual meeting of the Society for Investigative Dermatology.
There have been reports of gut microbiome dysbiosis associated with autoimmune diseases such as rheumatoid arthritis, diabetes, and celiac disease. “It is now clear that these events not just shape the immune response in the gut, but also distant sites and immune-privileged organs,” Tanya Sezin, a doctor of natural science from the University of Lübeck (Germany) and Columbia University, New York, said in her presentation.
Whether the gut microbiome may also play a role as an environmental factor in alopecia areata, another T-cell–mediated autoimmune disease for which there are few available treatment options, is being evaluated at the Christiano Laboratory at Columbia University, Dr. Sezin noted. “Much of the difficulty underlying the lack of an effective treatment has been the incomplete understanding of the pathogenesis of AA.”
She also referred to several case reports describing hair growth in patients who received fecal microbiota transplantation (FMT), including a 20-year-old with alopecia universalis, who experienced hair growth after receiving FMT for Crohn’s disease.
Dr. Sezin and colleagues at the lab first performed a study in mice to test whether the gut microbiome was involved in the pathogenesis of AA. Mice given an antibiotic cocktail of ampicillin, neomycin, and vancomycin prior to or at the time of a skin graft taken from a mouse model of AA to induce AA were protected from hair loss, while mice given the antibiotic cocktail after skin grafting were not protected from hair loss.
“16S rRNA sequencing analysis of the gut microbiota revealed a significant shift in gut microbiome composition in animals treated with antibiotics and protected from hair loss, as reflected by significant changes in alpha and beta diversity,” Dr. Sezin explained. “In AA mice, we also observed differential abundance of families from the Bacteroidetes and Firmicutes phyla.” Specifically, Lactobacillus murinus and Muribaculum intestinale were overrepresented in mice with AA.
The investigators then performed 16S rRNA sequencing on 26 patients with AA, who stopped treatment for 30 days beforehand, and 9 participants who did not have AA as controls. “Though we did not observe difference in alpha and beta diversity, we see changes in the relative abundance of several families belonging to the Firmicutes phyla,” in patients with AA, Dr. Sezin said.
In another cohort of 30 patients with AA and 20 participants without AA, who stopped treatment before the study, Dr. Sezin and colleagues found “differences in the relative abundance of members of the Firmicutes and Bacteroides phyla,” including Bacteroides caccae, Prevotella copri, Syntrophomonas wolfei, Blautia wexlerae, and Eubacterium eligens, she said. “Consistent with our findings, there are previous reports in the literature showing gut dysbiosis in several other autoimmune diseases associated with differential regulation of some of the top species we have identified.”
Dr. Sezin said her group is recruiting patients for a clinical trial evaluating FMT in patients with AA. “We plan to study the association between changes in the gut microbiome and immune cell composition in AA patients undergoing FMT,” she said. “Additionally, functional studies in mice are also currently [being conducted] to further pinpoint the contribution of gut microbiome to the pathogenesis of AA.”
When asked during the discussion session if there was any relationship between the skin microbiome and AA, Dr. Sezin said there was no connection found in mice studies, which she and her colleagues are investigating further. “In the human samples, we are currently recruiting more patients and healthy controls to try to get a better understanding of whether we see differences in the skin microbiome,” she added.
Dr. Sezin explained that how the gut microbiota “is really remediated in alopecia areata” is not well understood. “We think that it is possible that we see intestinal permeability in the gut due to the gut dysbiosis that we see in alopecia areata patients, and this might lead to systemic distribution of bacteria, which might cross-react or present cross reactivity with the antigens” identified in AA, which is also being investigated, she said.
FMT not a ‘simple fix’ for AA
Leslie Castelo-Soccio, MD, PhD, a dermatologist at the Children’s Hospital of Philadelphia, who was not involved with the research, said in an interview that the findings presented by Dr. Sezin show how AA shares similarities with other autoimmune diseases. “It does highlight how important the gut microbiome is to human disease, and that differences in relative abundance of bacteria play one part as a trigger in a genetically susceptible person.”
However, while some autoimmune diseases have a big difference in alpha and beta diversity, for example, “this has not been seen in people with alopecia areata,” Dr. Castelo-Soccio pointed out. “The differences are more subtle in terms of amounts of certain bacteria,” she said, noting that, in this study, the biggest differences were seen in the studies of mice.
Dr. Castelo-Soccio also said there may be also be differences in the gut microbiome in children and adults. “The gut microbiome shifts in very early childhood from a very diverse microbiome to a more ‘adult microbiome’ around age 4, which is the age we see the first peak of many autoimmune diseases, including alopecia areata. I think microbiome work in humans needs to focus on this transition point.”
As for the clinical trial at Columbia that is evaluating FMT in patients with AA, Dr. Castelo-Soccio said she is excited. “There is much to learn about fecal transplant for all diseases and about the role of the gut microbiome and environment. Most of what we know for fecal transplant centers on its use for Clostridium difficile infections.”
Patients and their families have been asking about the potential for FMT in alopecia area, Dr. Castelo-Soccio said, but some believe it is a “simple fix” when the reality is much more complex.
“When I speak to patients and families about this, I explain that currently the ‘active ingredient’ in fecal transplants is not definitively established. In any one donor, the community of bacteria is highly variable and can be from batch to batch. While the short-term risks are relatively low – cramping, diarrhea, discomfort, mode of delivery – there are reports of transmission of infectious bacteria from donors like [Escherichia] coli, which have led to severe infections.”
Long-term safety and durability of effects are also unclear, “so we do not know if a patient receiving one [FMT] will need many in the future. We do not know how changing the microbiome could affect the transplant recipient in terms of noninfectious diseases/disorders. We are learning about the role of microbiome in obesity, insulin resistance, mood disorders. We could be ‘fixing’ one trigger of alopecia but setting up [the] patient for other noninfectious conditions,” Dr. Castelo-Soccio said.
Dr. Sezin and Dr. Castelo-Soccio reported no relevant financial disclosures.
presented at the annual meeting of the Society for Investigative Dermatology.
There have been reports of gut microbiome dysbiosis associated with autoimmune diseases such as rheumatoid arthritis, diabetes, and celiac disease. “It is now clear that these events not just shape the immune response in the gut, but also distant sites and immune-privileged organs,” Tanya Sezin, a doctor of natural science from the University of Lübeck (Germany) and Columbia University, New York, said in her presentation.
Whether the gut microbiome may also play a role as an environmental factor in alopecia areata, another T-cell–mediated autoimmune disease for which there are few available treatment options, is being evaluated at the Christiano Laboratory at Columbia University, Dr. Sezin noted. “Much of the difficulty underlying the lack of an effective treatment has been the incomplete understanding of the pathogenesis of AA.”
She also referred to several case reports describing hair growth in patients who received fecal microbiota transplantation (FMT), including a 20-year-old with alopecia universalis, who experienced hair growth after receiving FMT for Crohn’s disease.
Dr. Sezin and colleagues at the lab first performed a study in mice to test whether the gut microbiome was involved in the pathogenesis of AA. Mice given an antibiotic cocktail of ampicillin, neomycin, and vancomycin prior to or at the time of a skin graft taken from a mouse model of AA to induce AA were protected from hair loss, while mice given the antibiotic cocktail after skin grafting were not protected from hair loss.
“16S rRNA sequencing analysis of the gut microbiota revealed a significant shift in gut microbiome composition in animals treated with antibiotics and protected from hair loss, as reflected by significant changes in alpha and beta diversity,” Dr. Sezin explained. “In AA mice, we also observed differential abundance of families from the Bacteroidetes and Firmicutes phyla.” Specifically, Lactobacillus murinus and Muribaculum intestinale were overrepresented in mice with AA.
The investigators then performed 16S rRNA sequencing on 26 patients with AA, who stopped treatment for 30 days beforehand, and 9 participants who did not have AA as controls. “Though we did not observe difference in alpha and beta diversity, we see changes in the relative abundance of several families belonging to the Firmicutes phyla,” in patients with AA, Dr. Sezin said.
In another cohort of 30 patients with AA and 20 participants without AA, who stopped treatment before the study, Dr. Sezin and colleagues found “differences in the relative abundance of members of the Firmicutes and Bacteroides phyla,” including Bacteroides caccae, Prevotella copri, Syntrophomonas wolfei, Blautia wexlerae, and Eubacterium eligens, she said. “Consistent with our findings, there are previous reports in the literature showing gut dysbiosis in several other autoimmune diseases associated with differential regulation of some of the top species we have identified.”
Dr. Sezin said her group is recruiting patients for a clinical trial evaluating FMT in patients with AA. “We plan to study the association between changes in the gut microbiome and immune cell composition in AA patients undergoing FMT,” she said. “Additionally, functional studies in mice are also currently [being conducted] to further pinpoint the contribution of gut microbiome to the pathogenesis of AA.”
When asked during the discussion session if there was any relationship between the skin microbiome and AA, Dr. Sezin said there was no connection found in mice studies, which she and her colleagues are investigating further. “In the human samples, we are currently recruiting more patients and healthy controls to try to get a better understanding of whether we see differences in the skin microbiome,” she added.
Dr. Sezin explained that how the gut microbiota “is really remediated in alopecia areata” is not well understood. “We think that it is possible that we see intestinal permeability in the gut due to the gut dysbiosis that we see in alopecia areata patients, and this might lead to systemic distribution of bacteria, which might cross-react or present cross reactivity with the antigens” identified in AA, which is also being investigated, she said.
FMT not a ‘simple fix’ for AA
Leslie Castelo-Soccio, MD, PhD, a dermatologist at the Children’s Hospital of Philadelphia, who was not involved with the research, said in an interview that the findings presented by Dr. Sezin show how AA shares similarities with other autoimmune diseases. “It does highlight how important the gut microbiome is to human disease, and that differences in relative abundance of bacteria play one part as a trigger in a genetically susceptible person.”
However, while some autoimmune diseases have a big difference in alpha and beta diversity, for example, “this has not been seen in people with alopecia areata,” Dr. Castelo-Soccio pointed out. “The differences are more subtle in terms of amounts of certain bacteria,” she said, noting that, in this study, the biggest differences were seen in the studies of mice.
Dr. Castelo-Soccio also said there may be also be differences in the gut microbiome in children and adults. “The gut microbiome shifts in very early childhood from a very diverse microbiome to a more ‘adult microbiome’ around age 4, which is the age we see the first peak of many autoimmune diseases, including alopecia areata. I think microbiome work in humans needs to focus on this transition point.”
As for the clinical trial at Columbia that is evaluating FMT in patients with AA, Dr. Castelo-Soccio said she is excited. “There is much to learn about fecal transplant for all diseases and about the role of the gut microbiome and environment. Most of what we know for fecal transplant centers on its use for Clostridium difficile infections.”
Patients and their families have been asking about the potential for FMT in alopecia area, Dr. Castelo-Soccio said, but some believe it is a “simple fix” when the reality is much more complex.
“When I speak to patients and families about this, I explain that currently the ‘active ingredient’ in fecal transplants is not definitively established. In any one donor, the community of bacteria is highly variable and can be from batch to batch. While the short-term risks are relatively low – cramping, diarrhea, discomfort, mode of delivery – there are reports of transmission of infectious bacteria from donors like [Escherichia] coli, which have led to severe infections.”
Long-term safety and durability of effects are also unclear, “so we do not know if a patient receiving one [FMT] will need many in the future. We do not know how changing the microbiome could affect the transplant recipient in terms of noninfectious diseases/disorders. We are learning about the role of microbiome in obesity, insulin resistance, mood disorders. We could be ‘fixing’ one trigger of alopecia but setting up [the] patient for other noninfectious conditions,” Dr. Castelo-Soccio said.
Dr. Sezin and Dr. Castelo-Soccio reported no relevant financial disclosures.
FROM SID 2021
Some patients with more severe PH in COPD may respond to treatment
Patients with pulmonary hypertension (PH) as a complication of chronic obstructive pulmonary disease (COPD) have worse functional impairment and higher mortality, compared with patients who have idiopathic pulmonary arterial hypertension (IPAH).
Despite these factors, some patients with more severe PH in COPD may respond to treatment and show clinical improvement after treatment, according to recent research published in the journal CHEST®.
Carmine Dario Vizza, MD, of the pulmonary hypertension unit, department of cardiovascular and respiratory diseases at Sapienza University of Rome, and colleagues evaluated patients in the Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension (COMPERA) database, enrolled up to August 2020, identifying 68 patients with moderate PH and COPD and 307 patients with severe PH and COPD. The researchers compared the PH and COPD groups with 307 patients who had idiopathic pulmonary arterial hypertension.
Overall, mostly older men made up the group of patients with moderate (50%; mean, 68.5 years) and severe PH in COPD (61%; mean 68.4 years), compared with those who had IPAH (37%; mean 61.7 years. Oral monotherapy for patients with PH and COPD was the main treatment, consisting of phosphodiesterase-5 inhibitors, while most patients with IPAH received endothelin receptor antagonists.
On functional tests, patients in the PH and COPD group tended to perform poorer on the 6-minute walking distance (6MWD) and World Health Organization functional class (WHO FC) than patients with IPAH. Specifically, among 42.7% of patients in both group for whom follow-up data were available, there was a similar frequency of improvement for 6MWD of 30 meters or more from baseline for both PH and COPD and IPAH groups (46.9% vs. 52.6%; P = .294), but there were significant differences between 6MWD between patients with moderate and severe PH and COPD (51.6% vs. 31.6%; P = .04). There was a nonsignificant improvement in WHO FC improvement of one or more classes for 65.6% of patients with PH and COPD and 58.3% of patients with IPAH with follow-up data available, with 28.5% of patients with PH in COPD improving compared with 35.8% of patients with IPAH (P = .078) and nonsignificant differences between moderate and severe PH and COPD (19.0% vs. 30.4%; P = .188).
Comparing outcomes
Follow-up data were available for 84% of patients with IPAH and 94% of patients with PH and COPD. Dr. Dario Vizza and colleagues found 45.7% of patients in the PH and COPD group and 24.9% of patients in the IPAH group died during follow-up, while 1.1% in the PH and COPD group and 1.5% of patients in the IPAH group underwent lung transplantations. For patients with moderate PH and COPD, 31.3% died and none underwent lung transplantation, while 49.0% of patients in the severe PH and COPD group died and 1.4% underwent lung transplantations.
Patients in the moderate PH and COPD group were more likely to discontinue treatment (10.9%), compared with patients with IPAH (6.6%) and patients with severe PH and COPD (5.2%). The most common reasons for discontinuations were tolerability and efficacy failure; the IPAH group had 63% of patients discontinue because of tolerability and 7% for efficacy failure, 47% of patients in the severe PH and COPD group discontinued because of tolerability and efficacy, and 29% discontinued treatment for tolerability and 57% for efficacy failure in the moderate and COPD group.
The researchers said male sex, low 6MWD, and high pulmonary vascular resistance at baseline were predictive of poorer outcomes for PH and COPD, but patients with more severe PH and COPD had better outcomes if they improved by 30 meters or more in 6MWD, or improved in WHO FC after receiving medical therapy. For patients with IPAH response to therapy was better among patients who were younger, had higher WHO FC, had high diffusing capacity of the lung for carbon monoxide, had high mean pulmonary artery pressure, and had low PCO2.
“Our data suggest that PH-targeted drug therapy in patients with COPD and severe PH may improve exercise tolerance and WHO FC in a subgroup of patients and that patients with COPD and PH who respond to therapy may have a better prognosis than patients who do not show clinical improvement. These findings need to be explored further in prospective, randomized controlled clinical studies,” the authors concluded.
More research needed
In a related editorial, James R. Klinger, MD, a pulmonologist with Brown University, Providence, R.I., and the director of the Rhode Island Hospital Pulmonary Hypertension Center in East Providence, said there is a “keen interest” in treating PH in COPD despite a lack of consistency on whether treatment is effective in this patient population. About 80% of PH centers in the United States treat PH in COPD when they treat conditions like lung disease with PAH medication, he pointed out. However, he questioned whether current medications designed for PAH could improve pulmonary hemodynamics for PH in COPD.
“Reasons that the pathobiologic condition of PH-COPD may differ from PAH include the likely exposure of the pulmonary circulation to greater degrees of hypoxia and hypercapnia and the greater loss of alveolar capillaries associated with emphysema,” he said.
The study by Dr. Dario Vizza and colleagues is an attempt to evaluate treatment response for patients with PH and COPD “in a way that allows comparison with patients who have been treated with similar drugs for PAH,” Dr. Klinger said. He noted the study’s retrospective nature, lack of control group, and lack of information on lung disease severity could limit the findings.
“These limitations preclude recommendations for the routine treatment of patients with PH-COPD, but the findings suggest that, despite greater morbidity at baseline, patients with PH-COPD may be nearly as likely to benefit from PAH medications as patients with IPAH,” he said.
“What is needed now is well-designed randomized controlled studies to determine whether improved outcomes can be achieved in this population and which patients are most likely to benefit,” he concluded. “Simply put: How bad does PH need to be in patients with COPD before treatment is helpful, and how severe does COPD need to be before PH treatment is futile?”
The authors reported personal and institutional relationships in the form of grants, consultancies, advisory board memberships, speakers bureau appointments, honoraria, patents, grant and research funding, lectures, travel compensation, and steering committee positions for a variety of pharmaceutical companies, agencies, societies, journals, medical publishing companies, and other organizations. Dr. Klinger reported his institution receives grant support from Acceleron and United Therapeutics in the area of PH, and he has been an unpaid consultant for Bayer.
Patients with pulmonary hypertension (PH) as a complication of chronic obstructive pulmonary disease (COPD) have worse functional impairment and higher mortality, compared with patients who have idiopathic pulmonary arterial hypertension (IPAH).
Despite these factors, some patients with more severe PH in COPD may respond to treatment and show clinical improvement after treatment, according to recent research published in the journal CHEST®.
Carmine Dario Vizza, MD, of the pulmonary hypertension unit, department of cardiovascular and respiratory diseases at Sapienza University of Rome, and colleagues evaluated patients in the Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension (COMPERA) database, enrolled up to August 2020, identifying 68 patients with moderate PH and COPD and 307 patients with severe PH and COPD. The researchers compared the PH and COPD groups with 307 patients who had idiopathic pulmonary arterial hypertension.
Overall, mostly older men made up the group of patients with moderate (50%; mean, 68.5 years) and severe PH in COPD (61%; mean 68.4 years), compared with those who had IPAH (37%; mean 61.7 years. Oral monotherapy for patients with PH and COPD was the main treatment, consisting of phosphodiesterase-5 inhibitors, while most patients with IPAH received endothelin receptor antagonists.
On functional tests, patients in the PH and COPD group tended to perform poorer on the 6-minute walking distance (6MWD) and World Health Organization functional class (WHO FC) than patients with IPAH. Specifically, among 42.7% of patients in both group for whom follow-up data were available, there was a similar frequency of improvement for 6MWD of 30 meters or more from baseline for both PH and COPD and IPAH groups (46.9% vs. 52.6%; P = .294), but there were significant differences between 6MWD between patients with moderate and severe PH and COPD (51.6% vs. 31.6%; P = .04). There was a nonsignificant improvement in WHO FC improvement of one or more classes for 65.6% of patients with PH and COPD and 58.3% of patients with IPAH with follow-up data available, with 28.5% of patients with PH in COPD improving compared with 35.8% of patients with IPAH (P = .078) and nonsignificant differences between moderate and severe PH and COPD (19.0% vs. 30.4%; P = .188).
Comparing outcomes
Follow-up data were available for 84% of patients with IPAH and 94% of patients with PH and COPD. Dr. Dario Vizza and colleagues found 45.7% of patients in the PH and COPD group and 24.9% of patients in the IPAH group died during follow-up, while 1.1% in the PH and COPD group and 1.5% of patients in the IPAH group underwent lung transplantations. For patients with moderate PH and COPD, 31.3% died and none underwent lung transplantation, while 49.0% of patients in the severe PH and COPD group died and 1.4% underwent lung transplantations.
Patients in the moderate PH and COPD group were more likely to discontinue treatment (10.9%), compared with patients with IPAH (6.6%) and patients with severe PH and COPD (5.2%). The most common reasons for discontinuations were tolerability and efficacy failure; the IPAH group had 63% of patients discontinue because of tolerability and 7% for efficacy failure, 47% of patients in the severe PH and COPD group discontinued because of tolerability and efficacy, and 29% discontinued treatment for tolerability and 57% for efficacy failure in the moderate and COPD group.
The researchers said male sex, low 6MWD, and high pulmonary vascular resistance at baseline were predictive of poorer outcomes for PH and COPD, but patients with more severe PH and COPD had better outcomes if they improved by 30 meters or more in 6MWD, or improved in WHO FC after receiving medical therapy. For patients with IPAH response to therapy was better among patients who were younger, had higher WHO FC, had high diffusing capacity of the lung for carbon monoxide, had high mean pulmonary artery pressure, and had low PCO2.
“Our data suggest that PH-targeted drug therapy in patients with COPD and severe PH may improve exercise tolerance and WHO FC in a subgroup of patients and that patients with COPD and PH who respond to therapy may have a better prognosis than patients who do not show clinical improvement. These findings need to be explored further in prospective, randomized controlled clinical studies,” the authors concluded.
More research needed
In a related editorial, James R. Klinger, MD, a pulmonologist with Brown University, Providence, R.I., and the director of the Rhode Island Hospital Pulmonary Hypertension Center in East Providence, said there is a “keen interest” in treating PH in COPD despite a lack of consistency on whether treatment is effective in this patient population. About 80% of PH centers in the United States treat PH in COPD when they treat conditions like lung disease with PAH medication, he pointed out. However, he questioned whether current medications designed for PAH could improve pulmonary hemodynamics for PH in COPD.
“Reasons that the pathobiologic condition of PH-COPD may differ from PAH include the likely exposure of the pulmonary circulation to greater degrees of hypoxia and hypercapnia and the greater loss of alveolar capillaries associated with emphysema,” he said.
The study by Dr. Dario Vizza and colleagues is an attempt to evaluate treatment response for patients with PH and COPD “in a way that allows comparison with patients who have been treated with similar drugs for PAH,” Dr. Klinger said. He noted the study’s retrospective nature, lack of control group, and lack of information on lung disease severity could limit the findings.
“These limitations preclude recommendations for the routine treatment of patients with PH-COPD, but the findings suggest that, despite greater morbidity at baseline, patients with PH-COPD may be nearly as likely to benefit from PAH medications as patients with IPAH,” he said.
“What is needed now is well-designed randomized controlled studies to determine whether improved outcomes can be achieved in this population and which patients are most likely to benefit,” he concluded. “Simply put: How bad does PH need to be in patients with COPD before treatment is helpful, and how severe does COPD need to be before PH treatment is futile?”
The authors reported personal and institutional relationships in the form of grants, consultancies, advisory board memberships, speakers bureau appointments, honoraria, patents, grant and research funding, lectures, travel compensation, and steering committee positions for a variety of pharmaceutical companies, agencies, societies, journals, medical publishing companies, and other organizations. Dr. Klinger reported his institution receives grant support from Acceleron and United Therapeutics in the area of PH, and he has been an unpaid consultant for Bayer.
Patients with pulmonary hypertension (PH) as a complication of chronic obstructive pulmonary disease (COPD) have worse functional impairment and higher mortality, compared with patients who have idiopathic pulmonary arterial hypertension (IPAH).
Despite these factors, some patients with more severe PH in COPD may respond to treatment and show clinical improvement after treatment, according to recent research published in the journal CHEST®.
Carmine Dario Vizza, MD, of the pulmonary hypertension unit, department of cardiovascular and respiratory diseases at Sapienza University of Rome, and colleagues evaluated patients in the Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension (COMPERA) database, enrolled up to August 2020, identifying 68 patients with moderate PH and COPD and 307 patients with severe PH and COPD. The researchers compared the PH and COPD groups with 307 patients who had idiopathic pulmonary arterial hypertension.
Overall, mostly older men made up the group of patients with moderate (50%; mean, 68.5 years) and severe PH in COPD (61%; mean 68.4 years), compared with those who had IPAH (37%; mean 61.7 years. Oral monotherapy for patients with PH and COPD was the main treatment, consisting of phosphodiesterase-5 inhibitors, while most patients with IPAH received endothelin receptor antagonists.
On functional tests, patients in the PH and COPD group tended to perform poorer on the 6-minute walking distance (6MWD) and World Health Organization functional class (WHO FC) than patients with IPAH. Specifically, among 42.7% of patients in both group for whom follow-up data were available, there was a similar frequency of improvement for 6MWD of 30 meters or more from baseline for both PH and COPD and IPAH groups (46.9% vs. 52.6%; P = .294), but there were significant differences between 6MWD between patients with moderate and severe PH and COPD (51.6% vs. 31.6%; P = .04). There was a nonsignificant improvement in WHO FC improvement of one or more classes for 65.6% of patients with PH and COPD and 58.3% of patients with IPAH with follow-up data available, with 28.5% of patients with PH in COPD improving compared with 35.8% of patients with IPAH (P = .078) and nonsignificant differences between moderate and severe PH and COPD (19.0% vs. 30.4%; P = .188).
Comparing outcomes
Follow-up data were available for 84% of patients with IPAH and 94% of patients with PH and COPD. Dr. Dario Vizza and colleagues found 45.7% of patients in the PH and COPD group and 24.9% of patients in the IPAH group died during follow-up, while 1.1% in the PH and COPD group and 1.5% of patients in the IPAH group underwent lung transplantations. For patients with moderate PH and COPD, 31.3% died and none underwent lung transplantation, while 49.0% of patients in the severe PH and COPD group died and 1.4% underwent lung transplantations.
Patients in the moderate PH and COPD group were more likely to discontinue treatment (10.9%), compared with patients with IPAH (6.6%) and patients with severe PH and COPD (5.2%). The most common reasons for discontinuations were tolerability and efficacy failure; the IPAH group had 63% of patients discontinue because of tolerability and 7% for efficacy failure, 47% of patients in the severe PH and COPD group discontinued because of tolerability and efficacy, and 29% discontinued treatment for tolerability and 57% for efficacy failure in the moderate and COPD group.
The researchers said male sex, low 6MWD, and high pulmonary vascular resistance at baseline were predictive of poorer outcomes for PH and COPD, but patients with more severe PH and COPD had better outcomes if they improved by 30 meters or more in 6MWD, or improved in WHO FC after receiving medical therapy. For patients with IPAH response to therapy was better among patients who were younger, had higher WHO FC, had high diffusing capacity of the lung for carbon monoxide, had high mean pulmonary artery pressure, and had low PCO2.
“Our data suggest that PH-targeted drug therapy in patients with COPD and severe PH may improve exercise tolerance and WHO FC in a subgroup of patients and that patients with COPD and PH who respond to therapy may have a better prognosis than patients who do not show clinical improvement. These findings need to be explored further in prospective, randomized controlled clinical studies,” the authors concluded.
More research needed
In a related editorial, James R. Klinger, MD, a pulmonologist with Brown University, Providence, R.I., and the director of the Rhode Island Hospital Pulmonary Hypertension Center in East Providence, said there is a “keen interest” in treating PH in COPD despite a lack of consistency on whether treatment is effective in this patient population. About 80% of PH centers in the United States treat PH in COPD when they treat conditions like lung disease with PAH medication, he pointed out. However, he questioned whether current medications designed for PAH could improve pulmonary hemodynamics for PH in COPD.
“Reasons that the pathobiologic condition of PH-COPD may differ from PAH include the likely exposure of the pulmonary circulation to greater degrees of hypoxia and hypercapnia and the greater loss of alveolar capillaries associated with emphysema,” he said.
The study by Dr. Dario Vizza and colleagues is an attempt to evaluate treatment response for patients with PH and COPD “in a way that allows comparison with patients who have been treated with similar drugs for PAH,” Dr. Klinger said. He noted the study’s retrospective nature, lack of control group, and lack of information on lung disease severity could limit the findings.
“These limitations preclude recommendations for the routine treatment of patients with PH-COPD, but the findings suggest that, despite greater morbidity at baseline, patients with PH-COPD may be nearly as likely to benefit from PAH medications as patients with IPAH,” he said.
“What is needed now is well-designed randomized controlled studies to determine whether improved outcomes can be achieved in this population and which patients are most likely to benefit,” he concluded. “Simply put: How bad does PH need to be in patients with COPD before treatment is helpful, and how severe does COPD need to be before PH treatment is futile?”
The authors reported personal and institutional relationships in the form of grants, consultancies, advisory board memberships, speakers bureau appointments, honoraria, patents, grant and research funding, lectures, travel compensation, and steering committee positions for a variety of pharmaceutical companies, agencies, societies, journals, medical publishing companies, and other organizations. Dr. Klinger reported his institution receives grant support from Acceleron and United Therapeutics in the area of PH, and he has been an unpaid consultant for Bayer.
FROM THE JOURNAL CHEST®
Indoor tanning ICD-10 codes may be underused, study finds
according to a study presented at the annual meeting of the Society for Investigative Dermatology.
“Since indoor tanning ICD-10 codes were only recently universally implemented in 2015, and providers may still be using other codes that cover similar services, we think our data likely underestimate the number of encounters and sequelae associated with indoor tanning,” Alexandria M. Brown, BSA, of Baylor College of Medicine, Houston, said in her presentation. “We think increased usage of these indoor tanning exposure codes in coming years will strengthen this body of indoor tanning literature and data.”
Using insurance claims data on about 43 million patients from Truven Health MarketScan, Ms. Brown and colleagues analyzed patient encounters with ICD-10 indoor tanning codes W89.1, W89.1XXA, W89.1XXD, and W89.1XXS between 2016 and 2018 for about 43 million patients. Overall, there were 4,550 patient encounters where these codes had been recorded, with most (99%) occurring in an outpatient setting. The majority of providers at these encounters were dermatologists (72%). Patients were mostly women (85%); and most were ages 25-34 years (19.4%), 35-44 years (20.6%), 45-54 years (22.7%), and 55-64 years (19%). Almost 5% were 65 and over, 11.7% were ages 18-24, and 1.6% were under age 18.
The use of indoor tanning codes were most common in the Midwest (55 per 100,000 encounters with dermatologists), compared with 16 per 100,000 in the Northeast, 21 per 100,000 in the West, and 28 per 100,000 in the South. CPT codes for “destruction of a premalignant lesion” and “biopsy” were the most frequently used codes entered at visits where indoor tanning codes were also entered, and were present in 15.1% of encounters and 18.4% of encounters, respectively.
“This suggests that many of these encounters may have been for skin cancer surveillance and that indoor tanning exposure may have been coded as part of a patient’s skin cancer risk profile,” Ms. Brown noted.
The study shows how these codes are being used and could help determine health care use patterns for these patients as well as their comorbidities, behaviors, and risk factors, according to the authors, who believe this is the first study to look at the use of ICD-10 indoor tanning codes.
“Any effort to reduce indoor tanning requires knowledge of the population at risk. It has been shown that the ability to recognize and provide counseling to at-risk patients can improve sun protective behaviors and reduce indoor tanning,” Ms. Brown said. Claims databases can be a “valuable tool to better understand patients who have been exposed to indoor tanning and their associated risk factors, comorbidities, behaviors, and health care utilization.”
In an interview, Adam Friedman, MD, professor and chair of dermatology at George Washington University, Washington, said the study was interesting and “provides some guidance with respect to who, when, and where in the U.S. to target educational initiatives on the harms of tanning beds.”
Dr. Friedman, who was not involved with the research, agreed with the authors’ assertion that their study was underestimating the use of indoor tanning beds. “Using a large database provides the means to better generalize one’s dataset; however in this case, it relies on proper coding by the practitioner,” or even using the code for tanning bed use at all.
“There also could be some inherent bias given most of the cases for which the code was used was for skin cancer surveillance, and therefore tanning bed use was top of mind,” he said.
While he believes this study may not be most efficient way of determining demographics of at-risk individuals using tanning beds, Dr. Friedman said the results “should serve as the impetus to develop public health campaigns around this information, following which research can be conducted to evaluate if the intervention had an impact.”
Ms. Brown and Dr. Friedman reported no relevant financial disclosures.
according to a study presented at the annual meeting of the Society for Investigative Dermatology.
“Since indoor tanning ICD-10 codes were only recently universally implemented in 2015, and providers may still be using other codes that cover similar services, we think our data likely underestimate the number of encounters and sequelae associated with indoor tanning,” Alexandria M. Brown, BSA, of Baylor College of Medicine, Houston, said in her presentation. “We think increased usage of these indoor tanning exposure codes in coming years will strengthen this body of indoor tanning literature and data.”
Using insurance claims data on about 43 million patients from Truven Health MarketScan, Ms. Brown and colleagues analyzed patient encounters with ICD-10 indoor tanning codes W89.1, W89.1XXA, W89.1XXD, and W89.1XXS between 2016 and 2018 for about 43 million patients. Overall, there were 4,550 patient encounters where these codes had been recorded, with most (99%) occurring in an outpatient setting. The majority of providers at these encounters were dermatologists (72%). Patients were mostly women (85%); and most were ages 25-34 years (19.4%), 35-44 years (20.6%), 45-54 years (22.7%), and 55-64 years (19%). Almost 5% were 65 and over, 11.7% were ages 18-24, and 1.6% were under age 18.
The use of indoor tanning codes were most common in the Midwest (55 per 100,000 encounters with dermatologists), compared with 16 per 100,000 in the Northeast, 21 per 100,000 in the West, and 28 per 100,000 in the South. CPT codes for “destruction of a premalignant lesion” and “biopsy” were the most frequently used codes entered at visits where indoor tanning codes were also entered, and were present in 15.1% of encounters and 18.4% of encounters, respectively.
“This suggests that many of these encounters may have been for skin cancer surveillance and that indoor tanning exposure may have been coded as part of a patient’s skin cancer risk profile,” Ms. Brown noted.
The study shows how these codes are being used and could help determine health care use patterns for these patients as well as their comorbidities, behaviors, and risk factors, according to the authors, who believe this is the first study to look at the use of ICD-10 indoor tanning codes.
“Any effort to reduce indoor tanning requires knowledge of the population at risk. It has been shown that the ability to recognize and provide counseling to at-risk patients can improve sun protective behaviors and reduce indoor tanning,” Ms. Brown said. Claims databases can be a “valuable tool to better understand patients who have been exposed to indoor tanning and their associated risk factors, comorbidities, behaviors, and health care utilization.”
In an interview, Adam Friedman, MD, professor and chair of dermatology at George Washington University, Washington, said the study was interesting and “provides some guidance with respect to who, when, and where in the U.S. to target educational initiatives on the harms of tanning beds.”
Dr. Friedman, who was not involved with the research, agreed with the authors’ assertion that their study was underestimating the use of indoor tanning beds. “Using a large database provides the means to better generalize one’s dataset; however in this case, it relies on proper coding by the practitioner,” or even using the code for tanning bed use at all.
“There also could be some inherent bias given most of the cases for which the code was used was for skin cancer surveillance, and therefore tanning bed use was top of mind,” he said.
While he believes this study may not be most efficient way of determining demographics of at-risk individuals using tanning beds, Dr. Friedman said the results “should serve as the impetus to develop public health campaigns around this information, following which research can be conducted to evaluate if the intervention had an impact.”
Ms. Brown and Dr. Friedman reported no relevant financial disclosures.
according to a study presented at the annual meeting of the Society for Investigative Dermatology.
“Since indoor tanning ICD-10 codes were only recently universally implemented in 2015, and providers may still be using other codes that cover similar services, we think our data likely underestimate the number of encounters and sequelae associated with indoor tanning,” Alexandria M. Brown, BSA, of Baylor College of Medicine, Houston, said in her presentation. “We think increased usage of these indoor tanning exposure codes in coming years will strengthen this body of indoor tanning literature and data.”
Using insurance claims data on about 43 million patients from Truven Health MarketScan, Ms. Brown and colleagues analyzed patient encounters with ICD-10 indoor tanning codes W89.1, W89.1XXA, W89.1XXD, and W89.1XXS between 2016 and 2018 for about 43 million patients. Overall, there were 4,550 patient encounters where these codes had been recorded, with most (99%) occurring in an outpatient setting. The majority of providers at these encounters were dermatologists (72%). Patients were mostly women (85%); and most were ages 25-34 years (19.4%), 35-44 years (20.6%), 45-54 years (22.7%), and 55-64 years (19%). Almost 5% were 65 and over, 11.7% were ages 18-24, and 1.6% were under age 18.
The use of indoor tanning codes were most common in the Midwest (55 per 100,000 encounters with dermatologists), compared with 16 per 100,000 in the Northeast, 21 per 100,000 in the West, and 28 per 100,000 in the South. CPT codes for “destruction of a premalignant lesion” and “biopsy” were the most frequently used codes entered at visits where indoor tanning codes were also entered, and were present in 15.1% of encounters and 18.4% of encounters, respectively.
“This suggests that many of these encounters may have been for skin cancer surveillance and that indoor tanning exposure may have been coded as part of a patient’s skin cancer risk profile,” Ms. Brown noted.
The study shows how these codes are being used and could help determine health care use patterns for these patients as well as their comorbidities, behaviors, and risk factors, according to the authors, who believe this is the first study to look at the use of ICD-10 indoor tanning codes.
“Any effort to reduce indoor tanning requires knowledge of the population at risk. It has been shown that the ability to recognize and provide counseling to at-risk patients can improve sun protective behaviors and reduce indoor tanning,” Ms. Brown said. Claims databases can be a “valuable tool to better understand patients who have been exposed to indoor tanning and their associated risk factors, comorbidities, behaviors, and health care utilization.”
In an interview, Adam Friedman, MD, professor and chair of dermatology at George Washington University, Washington, said the study was interesting and “provides some guidance with respect to who, when, and where in the U.S. to target educational initiatives on the harms of tanning beds.”
Dr. Friedman, who was not involved with the research, agreed with the authors’ assertion that their study was underestimating the use of indoor tanning beds. “Using a large database provides the means to better generalize one’s dataset; however in this case, it relies on proper coding by the practitioner,” or even using the code for tanning bed use at all.
“There also could be some inherent bias given most of the cases for which the code was used was for skin cancer surveillance, and therefore tanning bed use was top of mind,” he said.
While he believes this study may not be most efficient way of determining demographics of at-risk individuals using tanning beds, Dr. Friedman said the results “should serve as the impetus to develop public health campaigns around this information, following which research can be conducted to evaluate if the intervention had an impact.”
Ms. Brown and Dr. Friedman reported no relevant financial disclosures.
FROM SID 2021
Rate of cutaneous toxicities from ICIs may be lower than previously reported
A , according to research presented at the annual meeting of the Society for Investigative Dermatology, held virtually.
What’s more, many of the cutaneous immune-related adverse events (irAEs) from immune checkpoint inhibitors (ICIs) observed in the study may be unreported in clinical trial settings and by providers, according to one of the investigators, Yevgeniy Semenov, MD, MA, a dermatologist at Massachusetts General Hospital, Boston.
“Most cutaneous irAEs are low grade and might go unreported outside of clinical trial settings, as patients might not seek medical care, or when they do, providers might not report them in patient charts. As a result, the diagnoses identified in this study likely represent the most clinically relevant cutaneous events in the ICI population,” said Dr. Semenov, who presented the results at the meeting.
In the study, he said that one of the first issues he and his colleagues encountered was how to classify cutaneous irAEs, as they “can vary widely in morphology and severity.” Immune-related adverse events from ICIs are a “unique constellation of inflammatory toxicities,” affecting nearly every organ system, and may require treatment with immunosuppressive agents that can impact the effectiveness of the ICI. The matter is further complicated by a “lack of definitional standards of what constitutes a cutaneous immune-related adverse event, which greatly limits the research in this area,” Dr. Semenov said. There is also potential for misdiagnosis of irAEs as cutaneous eruptions occurring in patients receiving ICI therapy because of failure to account for the presence of skin disease at baseline, he pointed out.
Dr. Semenov noted that more than 40 cutaneous eruptions have been associated with ICI treatment. “Much of the observational data on cutaneous immune-related adverse events has been riddled with case reports and case series of cutaneous events that happen to be occurring in the setting of ICI therapy. These lack rigorous control groups and often associate events with little to no relationship to the actual ICI, which may have instead occurred in the setting of a competing medication,” he explained.
Real-world data
The researchers thus sought to identify the real-world incidence of cutaneous irAEs with population-level data. Using data from a national claims insurance database from January 2011 through 2019, they compared 8,637 of patients with cancer, treated with an ICI (who had not been treated with other cancer treatments within 6 months of starting an ICI) with 8,637 patients with cancer who were not treated with an ICI, matched for demographics, primary cancer type, and Charlson Comorbidity Index (CCI) score.
In both groups, the mean age of the patients was 67.5 years, 59.2% were men, and 93% had a severe CCI score. The most common cancer types were lung cancer (40%), melanoma (26.6%), and renal cell carcinoma (12.3%). The median follow-up time was 1.9 years, and the median treatment duration was 2.0 years.
Dr. Semenov and colleagues selected 42 dermatoses reported in the literature to evaluate and found an overall incidence of 25% within 2 years of starting ICI therapy. Of those 42 dermatoses, there were 10 with a significantly higher incidence among patients receiving ICIs, compared with controls: drug eruption or other nonspecific eruption (4.2%; incidence rate ratio, 5.00), bullous pemphigoid (0.3%; IRR, 4.91), maculopapular eruption (0.9%; IRR, 4.75), vitiligo (0.7%; IRR, 3.79), Grover’s disease (0.2%; IRR, 3.43), rash and other nonspecific eruption (9.0%; IRR, 2.34), mucositis (1.5%; IRR, 2.33), pruritus (4.8%; IRR, 1.92), lichen planus (0.5%; IRR, 1.75), and erythroderma (1.1%; IRR, 1.70).
After adjusting for a baseline history of squamous cell carcinoma and actinic keratosis, the researchers found that both were significantly less likely in patients receiving ICIs.
A delay in presentation of any cutaneous irAE after starting ICI therapy was also observed (a median of 16.1 weeks), which Dr. Semenov noted was longer than the 5 weeks reported in clinical trials. This delay in presentation increased to a median of 37.5 weeks for the 10 dermatoses with a significantly higher incidence among patients receiving ICIs, with 17.6% of patients presenting in the first month, 63.1% presenting by 6 months, and 84.6% presenting by 1 year.
Use of immunosuppressive treatment
The researchers also examined use of systemic immunosuppression for treating cutaneous toxicities, defined as “a new prescription for systemic glucocorticoids greater than 10 mg per day, prednisone equivalent, or nonsteroidal systemic immunosuppression,” administered within 7 days of the diagnosis of the cutaneous event. They found that 5% of patients overall received systemic immunosuppressive treatment within 7 days of a cutaneous event, which was “at the higher end of what was reported in clinical trials for the treatment of cutaneous toxicities,” Dr. Semenov noted.
“This is likely the result of the delays in diagnosis in nonclinical trial settings ... allowing more time for these events to progress to a higher grade. Also, there may be a greater willingness by providers to initiate systemic immunosuppression due to less stringent treatment protocols in real-world clinical settings,” he said.
Using a multivariable risk prediction model for cutaneous toxicities, the researchers identified use of ipilimumab, a CTLA-4-blocking antibody, as having a protective effect for not developing a cutaneous irAE, compared with the PD-1 blocker pembrolizumab (odds ratio, 0.78; 95% confidence interval, 0.62-0.98; P < .01). But combination ICI therapy (OR, 1.53; 95% CI, 1.25-1.88; P < .001), a melanoma diagnosis (OR, 2.47; 95% CI, 2.11-2.89; P < .001), and a renal cell carcinoma diagnosis (OR, 1.65; 95% CI, 1.36-2.00; P < .001) were found to be risk factors for developing cutaneous irAEs.
“The protective effect of ipilimumab identified in the study is interesting, as historically ipilimumab has been more likely to cause cutaneous toxicities,” Dr. Semenov said. “However, we believe that the majority of this association is mediated by the melanoma, for which ipilimumab was primarily used since its introduction. Independent of this relationship, it seems to be less likely to cause cutaneous toxicity than PD-1 inhibition, according to this data.”
Based on their findings, he said, “dermatologists can utilize this information to facilitate evaluations of high-risk patients so they can take steps to prevent progression to more severe toxicities and reduce reliance or systemic immunosuppression.”
The 25% real-world incidence of cutaneous irAEs observed in the study, Dr. Semenov said, is “somewhat lower than previous clinical trial estimates of over one-third of patients presenting with cutaneous toxicities” but he added that previous estimates were based primarily on studies of patients with melanoma.
That some patients delayed presentation with these conditions “should revise clinicians’ understanding of when to expect patients to present with these toxicities, and not to rule out a delayed onset of symptoms as being unrelated to immunotherapy,” Dr. Semenov said.
Most cutaneous irAEs are ‘manageable’
In an interview, Naiara Braghiroli, MD, PhD, a dermatologist at Baptist Health’s Miami Cancer Institute, Plantation, Fla., who was not an investigator in the study, noted that over the last decade, ICIs have “revolutionized the treatment of metastatic melanoma” and, more recently, the treatment of nonmelanoma skin cancers, with regard to survival rates and side effects.
She said that the results of the study show that “most of the cutaneous side effects are manageable with very few exceptions, like the cutaneous bullous disorders and rarely, more serious reactions [such as] Stevens-Johnson syndrome.”
The majority of the side effects are treatable “and when well controlled, the patient can have a good quality of life” during treatment, she added.
For future research, Dr. Braghiroli noted, it would be interesting to know more about whether the development of any specific cutaneous reaction associated with ICIs “is associated with a higher chance of good antitumor response,” as seen with other anticancer therapies such as epidermal growth factor receptor inhibitors.
Dr. Semenov and Dr. Braghiroli report having no relevant financial disclosures.
A , according to research presented at the annual meeting of the Society for Investigative Dermatology, held virtually.
What’s more, many of the cutaneous immune-related adverse events (irAEs) from immune checkpoint inhibitors (ICIs) observed in the study may be unreported in clinical trial settings and by providers, according to one of the investigators, Yevgeniy Semenov, MD, MA, a dermatologist at Massachusetts General Hospital, Boston.
“Most cutaneous irAEs are low grade and might go unreported outside of clinical trial settings, as patients might not seek medical care, or when they do, providers might not report them in patient charts. As a result, the diagnoses identified in this study likely represent the most clinically relevant cutaneous events in the ICI population,” said Dr. Semenov, who presented the results at the meeting.
In the study, he said that one of the first issues he and his colleagues encountered was how to classify cutaneous irAEs, as they “can vary widely in morphology and severity.” Immune-related adverse events from ICIs are a “unique constellation of inflammatory toxicities,” affecting nearly every organ system, and may require treatment with immunosuppressive agents that can impact the effectiveness of the ICI. The matter is further complicated by a “lack of definitional standards of what constitutes a cutaneous immune-related adverse event, which greatly limits the research in this area,” Dr. Semenov said. There is also potential for misdiagnosis of irAEs as cutaneous eruptions occurring in patients receiving ICI therapy because of failure to account for the presence of skin disease at baseline, he pointed out.
Dr. Semenov noted that more than 40 cutaneous eruptions have been associated with ICI treatment. “Much of the observational data on cutaneous immune-related adverse events has been riddled with case reports and case series of cutaneous events that happen to be occurring in the setting of ICI therapy. These lack rigorous control groups and often associate events with little to no relationship to the actual ICI, which may have instead occurred in the setting of a competing medication,” he explained.
Real-world data
The researchers thus sought to identify the real-world incidence of cutaneous irAEs with population-level data. Using data from a national claims insurance database from January 2011 through 2019, they compared 8,637 of patients with cancer, treated with an ICI (who had not been treated with other cancer treatments within 6 months of starting an ICI) with 8,637 patients with cancer who were not treated with an ICI, matched for demographics, primary cancer type, and Charlson Comorbidity Index (CCI) score.
In both groups, the mean age of the patients was 67.5 years, 59.2% were men, and 93% had a severe CCI score. The most common cancer types were lung cancer (40%), melanoma (26.6%), and renal cell carcinoma (12.3%). The median follow-up time was 1.9 years, and the median treatment duration was 2.0 years.
Dr. Semenov and colleagues selected 42 dermatoses reported in the literature to evaluate and found an overall incidence of 25% within 2 years of starting ICI therapy. Of those 42 dermatoses, there were 10 with a significantly higher incidence among patients receiving ICIs, compared with controls: drug eruption or other nonspecific eruption (4.2%; incidence rate ratio, 5.00), bullous pemphigoid (0.3%; IRR, 4.91), maculopapular eruption (0.9%; IRR, 4.75), vitiligo (0.7%; IRR, 3.79), Grover’s disease (0.2%; IRR, 3.43), rash and other nonspecific eruption (9.0%; IRR, 2.34), mucositis (1.5%; IRR, 2.33), pruritus (4.8%; IRR, 1.92), lichen planus (0.5%; IRR, 1.75), and erythroderma (1.1%; IRR, 1.70).
After adjusting for a baseline history of squamous cell carcinoma and actinic keratosis, the researchers found that both were significantly less likely in patients receiving ICIs.
A delay in presentation of any cutaneous irAE after starting ICI therapy was also observed (a median of 16.1 weeks), which Dr. Semenov noted was longer than the 5 weeks reported in clinical trials. This delay in presentation increased to a median of 37.5 weeks for the 10 dermatoses with a significantly higher incidence among patients receiving ICIs, with 17.6% of patients presenting in the first month, 63.1% presenting by 6 months, and 84.6% presenting by 1 year.
Use of immunosuppressive treatment
The researchers also examined use of systemic immunosuppression for treating cutaneous toxicities, defined as “a new prescription for systemic glucocorticoids greater than 10 mg per day, prednisone equivalent, or nonsteroidal systemic immunosuppression,” administered within 7 days of the diagnosis of the cutaneous event. They found that 5% of patients overall received systemic immunosuppressive treatment within 7 days of a cutaneous event, which was “at the higher end of what was reported in clinical trials for the treatment of cutaneous toxicities,” Dr. Semenov noted.
“This is likely the result of the delays in diagnosis in nonclinical trial settings ... allowing more time for these events to progress to a higher grade. Also, there may be a greater willingness by providers to initiate systemic immunosuppression due to less stringent treatment protocols in real-world clinical settings,” he said.
Using a multivariable risk prediction model for cutaneous toxicities, the researchers identified use of ipilimumab, a CTLA-4-blocking antibody, as having a protective effect for not developing a cutaneous irAE, compared with the PD-1 blocker pembrolizumab (odds ratio, 0.78; 95% confidence interval, 0.62-0.98; P < .01). But combination ICI therapy (OR, 1.53; 95% CI, 1.25-1.88; P < .001), a melanoma diagnosis (OR, 2.47; 95% CI, 2.11-2.89; P < .001), and a renal cell carcinoma diagnosis (OR, 1.65; 95% CI, 1.36-2.00; P < .001) were found to be risk factors for developing cutaneous irAEs.
“The protective effect of ipilimumab identified in the study is interesting, as historically ipilimumab has been more likely to cause cutaneous toxicities,” Dr. Semenov said. “However, we believe that the majority of this association is mediated by the melanoma, for which ipilimumab was primarily used since its introduction. Independent of this relationship, it seems to be less likely to cause cutaneous toxicity than PD-1 inhibition, according to this data.”
Based on their findings, he said, “dermatologists can utilize this information to facilitate evaluations of high-risk patients so they can take steps to prevent progression to more severe toxicities and reduce reliance or systemic immunosuppression.”
The 25% real-world incidence of cutaneous irAEs observed in the study, Dr. Semenov said, is “somewhat lower than previous clinical trial estimates of over one-third of patients presenting with cutaneous toxicities” but he added that previous estimates were based primarily on studies of patients with melanoma.
That some patients delayed presentation with these conditions “should revise clinicians’ understanding of when to expect patients to present with these toxicities, and not to rule out a delayed onset of symptoms as being unrelated to immunotherapy,” Dr. Semenov said.
Most cutaneous irAEs are ‘manageable’
In an interview, Naiara Braghiroli, MD, PhD, a dermatologist at Baptist Health’s Miami Cancer Institute, Plantation, Fla., who was not an investigator in the study, noted that over the last decade, ICIs have “revolutionized the treatment of metastatic melanoma” and, more recently, the treatment of nonmelanoma skin cancers, with regard to survival rates and side effects.
She said that the results of the study show that “most of the cutaneous side effects are manageable with very few exceptions, like the cutaneous bullous disorders and rarely, more serious reactions [such as] Stevens-Johnson syndrome.”
The majority of the side effects are treatable “and when well controlled, the patient can have a good quality of life” during treatment, she added.
For future research, Dr. Braghiroli noted, it would be interesting to know more about whether the development of any specific cutaneous reaction associated with ICIs “is associated with a higher chance of good antitumor response,” as seen with other anticancer therapies such as epidermal growth factor receptor inhibitors.
Dr. Semenov and Dr. Braghiroli report having no relevant financial disclosures.
A , according to research presented at the annual meeting of the Society for Investigative Dermatology, held virtually.
What’s more, many of the cutaneous immune-related adverse events (irAEs) from immune checkpoint inhibitors (ICIs) observed in the study may be unreported in clinical trial settings and by providers, according to one of the investigators, Yevgeniy Semenov, MD, MA, a dermatologist at Massachusetts General Hospital, Boston.
“Most cutaneous irAEs are low grade and might go unreported outside of clinical trial settings, as patients might not seek medical care, or when they do, providers might not report them in patient charts. As a result, the diagnoses identified in this study likely represent the most clinically relevant cutaneous events in the ICI population,” said Dr. Semenov, who presented the results at the meeting.
In the study, he said that one of the first issues he and his colleagues encountered was how to classify cutaneous irAEs, as they “can vary widely in morphology and severity.” Immune-related adverse events from ICIs are a “unique constellation of inflammatory toxicities,” affecting nearly every organ system, and may require treatment with immunosuppressive agents that can impact the effectiveness of the ICI. The matter is further complicated by a “lack of definitional standards of what constitutes a cutaneous immune-related adverse event, which greatly limits the research in this area,” Dr. Semenov said. There is also potential for misdiagnosis of irAEs as cutaneous eruptions occurring in patients receiving ICI therapy because of failure to account for the presence of skin disease at baseline, he pointed out.
Dr. Semenov noted that more than 40 cutaneous eruptions have been associated with ICI treatment. “Much of the observational data on cutaneous immune-related adverse events has been riddled with case reports and case series of cutaneous events that happen to be occurring in the setting of ICI therapy. These lack rigorous control groups and often associate events with little to no relationship to the actual ICI, which may have instead occurred in the setting of a competing medication,” he explained.
Real-world data
The researchers thus sought to identify the real-world incidence of cutaneous irAEs with population-level data. Using data from a national claims insurance database from January 2011 through 2019, they compared 8,637 of patients with cancer, treated with an ICI (who had not been treated with other cancer treatments within 6 months of starting an ICI) with 8,637 patients with cancer who were not treated with an ICI, matched for demographics, primary cancer type, and Charlson Comorbidity Index (CCI) score.
In both groups, the mean age of the patients was 67.5 years, 59.2% were men, and 93% had a severe CCI score. The most common cancer types were lung cancer (40%), melanoma (26.6%), and renal cell carcinoma (12.3%). The median follow-up time was 1.9 years, and the median treatment duration was 2.0 years.
Dr. Semenov and colleagues selected 42 dermatoses reported in the literature to evaluate and found an overall incidence of 25% within 2 years of starting ICI therapy. Of those 42 dermatoses, there were 10 with a significantly higher incidence among patients receiving ICIs, compared with controls: drug eruption or other nonspecific eruption (4.2%; incidence rate ratio, 5.00), bullous pemphigoid (0.3%; IRR, 4.91), maculopapular eruption (0.9%; IRR, 4.75), vitiligo (0.7%; IRR, 3.79), Grover’s disease (0.2%; IRR, 3.43), rash and other nonspecific eruption (9.0%; IRR, 2.34), mucositis (1.5%; IRR, 2.33), pruritus (4.8%; IRR, 1.92), lichen planus (0.5%; IRR, 1.75), and erythroderma (1.1%; IRR, 1.70).
After adjusting for a baseline history of squamous cell carcinoma and actinic keratosis, the researchers found that both were significantly less likely in patients receiving ICIs.
A delay in presentation of any cutaneous irAE after starting ICI therapy was also observed (a median of 16.1 weeks), which Dr. Semenov noted was longer than the 5 weeks reported in clinical trials. This delay in presentation increased to a median of 37.5 weeks for the 10 dermatoses with a significantly higher incidence among patients receiving ICIs, with 17.6% of patients presenting in the first month, 63.1% presenting by 6 months, and 84.6% presenting by 1 year.
Use of immunosuppressive treatment
The researchers also examined use of systemic immunosuppression for treating cutaneous toxicities, defined as “a new prescription for systemic glucocorticoids greater than 10 mg per day, prednisone equivalent, or nonsteroidal systemic immunosuppression,” administered within 7 days of the diagnosis of the cutaneous event. They found that 5% of patients overall received systemic immunosuppressive treatment within 7 days of a cutaneous event, which was “at the higher end of what was reported in clinical trials for the treatment of cutaneous toxicities,” Dr. Semenov noted.
“This is likely the result of the delays in diagnosis in nonclinical trial settings ... allowing more time for these events to progress to a higher grade. Also, there may be a greater willingness by providers to initiate systemic immunosuppression due to less stringent treatment protocols in real-world clinical settings,” he said.
Using a multivariable risk prediction model for cutaneous toxicities, the researchers identified use of ipilimumab, a CTLA-4-blocking antibody, as having a protective effect for not developing a cutaneous irAE, compared with the PD-1 blocker pembrolizumab (odds ratio, 0.78; 95% confidence interval, 0.62-0.98; P < .01). But combination ICI therapy (OR, 1.53; 95% CI, 1.25-1.88; P < .001), a melanoma diagnosis (OR, 2.47; 95% CI, 2.11-2.89; P < .001), and a renal cell carcinoma diagnosis (OR, 1.65; 95% CI, 1.36-2.00; P < .001) were found to be risk factors for developing cutaneous irAEs.
“The protective effect of ipilimumab identified in the study is interesting, as historically ipilimumab has been more likely to cause cutaneous toxicities,” Dr. Semenov said. “However, we believe that the majority of this association is mediated by the melanoma, for which ipilimumab was primarily used since its introduction. Independent of this relationship, it seems to be less likely to cause cutaneous toxicity than PD-1 inhibition, according to this data.”
Based on their findings, he said, “dermatologists can utilize this information to facilitate evaluations of high-risk patients so they can take steps to prevent progression to more severe toxicities and reduce reliance or systemic immunosuppression.”
The 25% real-world incidence of cutaneous irAEs observed in the study, Dr. Semenov said, is “somewhat lower than previous clinical trial estimates of over one-third of patients presenting with cutaneous toxicities” but he added that previous estimates were based primarily on studies of patients with melanoma.
That some patients delayed presentation with these conditions “should revise clinicians’ understanding of when to expect patients to present with these toxicities, and not to rule out a delayed onset of symptoms as being unrelated to immunotherapy,” Dr. Semenov said.
Most cutaneous irAEs are ‘manageable’
In an interview, Naiara Braghiroli, MD, PhD, a dermatologist at Baptist Health’s Miami Cancer Institute, Plantation, Fla., who was not an investigator in the study, noted that over the last decade, ICIs have “revolutionized the treatment of metastatic melanoma” and, more recently, the treatment of nonmelanoma skin cancers, with regard to survival rates and side effects.
She said that the results of the study show that “most of the cutaneous side effects are manageable with very few exceptions, like the cutaneous bullous disorders and rarely, more serious reactions [such as] Stevens-Johnson syndrome.”
The majority of the side effects are treatable “and when well controlled, the patient can have a good quality of life” during treatment, she added.
For future research, Dr. Braghiroli noted, it would be interesting to know more about whether the development of any specific cutaneous reaction associated with ICIs “is associated with a higher chance of good antitumor response,” as seen with other anticancer therapies such as epidermal growth factor receptor inhibitors.
Dr. Semenov and Dr. Braghiroli report having no relevant financial disclosures.
FROM SID 2021
Topical histone deacetylase inhibitor reduced BCC size in phase 2 study
according to research presented at the annual meeting of the Society for Investigative Dermatology.
“Our results demonstrate a clinically significant decrease in tumor size in response to 6 weeks of topical 1% remetinostat therapy in 70% of per-protocol tumors, with 55% reaching complete pathological resolution,” James M. Kilgour, MD, a postdoctoral research fellow at the Sarin Lab at Stanford (Calif.) University, said at the meeting.
Surgical excision is the preferred treatment for BCC, but there is still a need for noninvasive treatment options, Dr. Kilgour said. “Given the potential morbidity associated with excision, particularly for patients experiencing multiple or recurrent tumors, such as the immunosuppressed or patients with Gorlin syndrome, an effective and tolerable topical therapy would be a significant benefit,” he noted.
Previously, in an in silico screen experiment, Dr. Kilgour and colleagues identified HDAC inhibitors as a “top predicted therapeutic” for BCC treatment, and found that in mice studies, HDAC inhibitors were able to suppress the growth of BCC cell lines and BCC allografts.
Remetinostat, a pan-HDAC inhibitor, is being investigated as a treatment for cutaneous T-cell lymphoma.
HDAC inhibitors are thought to “alter expression of key oncogenes and tumor suppressors through epigenetic modification of histone and nonhistone proteins,” he noted.
To evaluate the efficacy of topical remetinostat for BCC, the investigators enrolled 30 patients with 49 BCC tumors in a phase 2, open-label, single-arm trial. Participants had tumors that were greater than 5 mm in diameter and had been referred to surgery at Stanford before enrollment. Patients were a mean of 59 years old, 63% were men, and 90% were White; 59.2% of participants had tumors with a diameter greater than 10 mm, the rest had tumors with a diameter of 10 mm or less.
After the tumors were photographed and measured, participants received 6 weeks of topical remetinostat therapy, followed by final measurement and photography of the tumors at 8 weeks and surgical excision. Topical remetinostat 1% gel was applied three times per day under bandage occlusion.
Overall, 25 participants with 33 tumors were included in the per-protocol analysis. At 8 weeks, there was at least a 30% decrease in diameter from baseline for 69.7% of tumors in these patients, with 17 of 33 tumors showing a complete response by week 8.
Regarding tumor subtypes, there was a 100% overall response rate for the 6 superficial BCC tumors (1 partial response, 5 complete responses), a 68.2% ORR for the 22 nodular tumors (5 partial responses, 10 complete responses), and a 66.7% ORR for the 3 infiltrative tumors (no partial responses, 2 complete responses). There were no partial or complete responses for the two micronodular tumors.
Most adverse events in the study were localized drug reactions, with no serious or systemic adverse events, Dr. Kilgour noted, with 10 tumors demonstrating either no reaction or a grade 1 reaction, and 23 tumors having a grade 2 or grade 3 response.
The investigators also used imaging (ImageJ) software to evaluate the average decrease in cross-sectional tumor area. The results of the analysis showed an average decrease at 8 weeks from baseline of 71.5%. In addition, histological assessment at 8 weeks demonstrated that 54.8% of tumors had complete pathological resolution.
“In the future, we advocate for a follow-up blinded, randomized, controlled trial of remetinostat with greater participant diversity,” Dr. Kilgour said. “Specifically, greater power is needed to understand which histological subtypes of BCC will respond best to the treatment and we need to understand the long-term durability of tumor resolution.”
Remetinostat promising as topical BCC therapy
In an interview, Beth G. Goldstein, MD, a dermatologist and Mohs surgeon in Chapel Hill, N.C., noted that the preliminary study was “an exciting report of a safe, well-tolerated nonsurgical option for patients with superficial BCCs on the trunk and extremities,” which has potential to be used in the future for nonsuperficial BCCs. The study shows that superficial BCCs can respond at a rate of 100% on nonfacial areas, said Dr. Goldstein, who was not involved in the research. “These lesions can be quite large with higher chances of recurrence and difficulty with wound care.
“This type of directed therapy hopefully continues to be perfected for treatment of BCC that avoids scarring and is well tolerated,” she added.
Dr. Goldstein commented that complete pathological resolution of 54.8% “was still unacceptably low for the remaining tumor types.” For those cases, she said remetinostat could possibly “provide a topical option as an adjunctive treatment for potentially reducing the size of the BCC prior to surgical removal,” as an alternative to a systemic therapy like vismodegib (Erivedge).
Dr. Goldstein said the strengths of the study were in the variety of tumors, close follow-up with histologic evaluation and safety signals. In terms of limitations, she said whether there were any cases of Gorlin syndrome was not clear. In addition, at least 30% of BCCs have a mixed tumor type on Mohs surgery that differs from the original biopsy, and “there was no mention if the residual tumor remained with the same histology,” she said.
In the future, a large, randomized trial is warranted to stratify for Gorlin syndrome, patients who are immunosuppressed, and additional tumor types that were underrepresented in this study, such as micronodular tumors, Dr. Goldstein said. Future studies also should examine how remetinostat impacts BCC in facial areas, the effect of multiple applications, and how the therapy performs as an adjunctive treatment before surgery.
This study was funded by Medivir, the Damon Runyon Foundation, National Cancer Institute, an American Skin Association Hambrick Medical Student grant, and Stanford Medical Scholars. Dr. Kilgour and Dr. Goldstein reported no relevant financial disclosures.
according to research presented at the annual meeting of the Society for Investigative Dermatology.
“Our results demonstrate a clinically significant decrease in tumor size in response to 6 weeks of topical 1% remetinostat therapy in 70% of per-protocol tumors, with 55% reaching complete pathological resolution,” James M. Kilgour, MD, a postdoctoral research fellow at the Sarin Lab at Stanford (Calif.) University, said at the meeting.
Surgical excision is the preferred treatment for BCC, but there is still a need for noninvasive treatment options, Dr. Kilgour said. “Given the potential morbidity associated with excision, particularly for patients experiencing multiple or recurrent tumors, such as the immunosuppressed or patients with Gorlin syndrome, an effective and tolerable topical therapy would be a significant benefit,” he noted.
Previously, in an in silico screen experiment, Dr. Kilgour and colleagues identified HDAC inhibitors as a “top predicted therapeutic” for BCC treatment, and found that in mice studies, HDAC inhibitors were able to suppress the growth of BCC cell lines and BCC allografts.
Remetinostat, a pan-HDAC inhibitor, is being investigated as a treatment for cutaneous T-cell lymphoma.
HDAC inhibitors are thought to “alter expression of key oncogenes and tumor suppressors through epigenetic modification of histone and nonhistone proteins,” he noted.
To evaluate the efficacy of topical remetinostat for BCC, the investigators enrolled 30 patients with 49 BCC tumors in a phase 2, open-label, single-arm trial. Participants had tumors that were greater than 5 mm in diameter and had been referred to surgery at Stanford before enrollment. Patients were a mean of 59 years old, 63% were men, and 90% were White; 59.2% of participants had tumors with a diameter greater than 10 mm, the rest had tumors with a diameter of 10 mm or less.
After the tumors were photographed and measured, participants received 6 weeks of topical remetinostat therapy, followed by final measurement and photography of the tumors at 8 weeks and surgical excision. Topical remetinostat 1% gel was applied three times per day under bandage occlusion.
Overall, 25 participants with 33 tumors were included in the per-protocol analysis. At 8 weeks, there was at least a 30% decrease in diameter from baseline for 69.7% of tumors in these patients, with 17 of 33 tumors showing a complete response by week 8.
Regarding tumor subtypes, there was a 100% overall response rate for the 6 superficial BCC tumors (1 partial response, 5 complete responses), a 68.2% ORR for the 22 nodular tumors (5 partial responses, 10 complete responses), and a 66.7% ORR for the 3 infiltrative tumors (no partial responses, 2 complete responses). There were no partial or complete responses for the two micronodular tumors.
Most adverse events in the study were localized drug reactions, with no serious or systemic adverse events, Dr. Kilgour noted, with 10 tumors demonstrating either no reaction or a grade 1 reaction, and 23 tumors having a grade 2 or grade 3 response.
The investigators also used imaging (ImageJ) software to evaluate the average decrease in cross-sectional tumor area. The results of the analysis showed an average decrease at 8 weeks from baseline of 71.5%. In addition, histological assessment at 8 weeks demonstrated that 54.8% of tumors had complete pathological resolution.
“In the future, we advocate for a follow-up blinded, randomized, controlled trial of remetinostat with greater participant diversity,” Dr. Kilgour said. “Specifically, greater power is needed to understand which histological subtypes of BCC will respond best to the treatment and we need to understand the long-term durability of tumor resolution.”
Remetinostat promising as topical BCC therapy
In an interview, Beth G. Goldstein, MD, a dermatologist and Mohs surgeon in Chapel Hill, N.C., noted that the preliminary study was “an exciting report of a safe, well-tolerated nonsurgical option for patients with superficial BCCs on the trunk and extremities,” which has potential to be used in the future for nonsuperficial BCCs. The study shows that superficial BCCs can respond at a rate of 100% on nonfacial areas, said Dr. Goldstein, who was not involved in the research. “These lesions can be quite large with higher chances of recurrence and difficulty with wound care.
“This type of directed therapy hopefully continues to be perfected for treatment of BCC that avoids scarring and is well tolerated,” she added.
Dr. Goldstein commented that complete pathological resolution of 54.8% “was still unacceptably low for the remaining tumor types.” For those cases, she said remetinostat could possibly “provide a topical option as an adjunctive treatment for potentially reducing the size of the BCC prior to surgical removal,” as an alternative to a systemic therapy like vismodegib (Erivedge).
Dr. Goldstein said the strengths of the study were in the variety of tumors, close follow-up with histologic evaluation and safety signals. In terms of limitations, she said whether there were any cases of Gorlin syndrome was not clear. In addition, at least 30% of BCCs have a mixed tumor type on Mohs surgery that differs from the original biopsy, and “there was no mention if the residual tumor remained with the same histology,” she said.
In the future, a large, randomized trial is warranted to stratify for Gorlin syndrome, patients who are immunosuppressed, and additional tumor types that were underrepresented in this study, such as micronodular tumors, Dr. Goldstein said. Future studies also should examine how remetinostat impacts BCC in facial areas, the effect of multiple applications, and how the therapy performs as an adjunctive treatment before surgery.
This study was funded by Medivir, the Damon Runyon Foundation, National Cancer Institute, an American Skin Association Hambrick Medical Student grant, and Stanford Medical Scholars. Dr. Kilgour and Dr. Goldstein reported no relevant financial disclosures.
according to research presented at the annual meeting of the Society for Investigative Dermatology.
“Our results demonstrate a clinically significant decrease in tumor size in response to 6 weeks of topical 1% remetinostat therapy in 70% of per-protocol tumors, with 55% reaching complete pathological resolution,” James M. Kilgour, MD, a postdoctoral research fellow at the Sarin Lab at Stanford (Calif.) University, said at the meeting.
Surgical excision is the preferred treatment for BCC, but there is still a need for noninvasive treatment options, Dr. Kilgour said. “Given the potential morbidity associated with excision, particularly for patients experiencing multiple or recurrent tumors, such as the immunosuppressed or patients with Gorlin syndrome, an effective and tolerable topical therapy would be a significant benefit,” he noted.
Previously, in an in silico screen experiment, Dr. Kilgour and colleagues identified HDAC inhibitors as a “top predicted therapeutic” for BCC treatment, and found that in mice studies, HDAC inhibitors were able to suppress the growth of BCC cell lines and BCC allografts.
Remetinostat, a pan-HDAC inhibitor, is being investigated as a treatment for cutaneous T-cell lymphoma.
HDAC inhibitors are thought to “alter expression of key oncogenes and tumor suppressors through epigenetic modification of histone and nonhistone proteins,” he noted.
To evaluate the efficacy of topical remetinostat for BCC, the investigators enrolled 30 patients with 49 BCC tumors in a phase 2, open-label, single-arm trial. Participants had tumors that were greater than 5 mm in diameter and had been referred to surgery at Stanford before enrollment. Patients were a mean of 59 years old, 63% were men, and 90% were White; 59.2% of participants had tumors with a diameter greater than 10 mm, the rest had tumors with a diameter of 10 mm or less.
After the tumors were photographed and measured, participants received 6 weeks of topical remetinostat therapy, followed by final measurement and photography of the tumors at 8 weeks and surgical excision. Topical remetinostat 1% gel was applied three times per day under bandage occlusion.
Overall, 25 participants with 33 tumors were included in the per-protocol analysis. At 8 weeks, there was at least a 30% decrease in diameter from baseline for 69.7% of tumors in these patients, with 17 of 33 tumors showing a complete response by week 8.
Regarding tumor subtypes, there was a 100% overall response rate for the 6 superficial BCC tumors (1 partial response, 5 complete responses), a 68.2% ORR for the 22 nodular tumors (5 partial responses, 10 complete responses), and a 66.7% ORR for the 3 infiltrative tumors (no partial responses, 2 complete responses). There were no partial or complete responses for the two micronodular tumors.
Most adverse events in the study were localized drug reactions, with no serious or systemic adverse events, Dr. Kilgour noted, with 10 tumors demonstrating either no reaction or a grade 1 reaction, and 23 tumors having a grade 2 or grade 3 response.
The investigators also used imaging (ImageJ) software to evaluate the average decrease in cross-sectional tumor area. The results of the analysis showed an average decrease at 8 weeks from baseline of 71.5%. In addition, histological assessment at 8 weeks demonstrated that 54.8% of tumors had complete pathological resolution.
“In the future, we advocate for a follow-up blinded, randomized, controlled trial of remetinostat with greater participant diversity,” Dr. Kilgour said. “Specifically, greater power is needed to understand which histological subtypes of BCC will respond best to the treatment and we need to understand the long-term durability of tumor resolution.”
Remetinostat promising as topical BCC therapy
In an interview, Beth G. Goldstein, MD, a dermatologist and Mohs surgeon in Chapel Hill, N.C., noted that the preliminary study was “an exciting report of a safe, well-tolerated nonsurgical option for patients with superficial BCCs on the trunk and extremities,” which has potential to be used in the future for nonsuperficial BCCs. The study shows that superficial BCCs can respond at a rate of 100% on nonfacial areas, said Dr. Goldstein, who was not involved in the research. “These lesions can be quite large with higher chances of recurrence and difficulty with wound care.
“This type of directed therapy hopefully continues to be perfected for treatment of BCC that avoids scarring and is well tolerated,” she added.
Dr. Goldstein commented that complete pathological resolution of 54.8% “was still unacceptably low for the remaining tumor types.” For those cases, she said remetinostat could possibly “provide a topical option as an adjunctive treatment for potentially reducing the size of the BCC prior to surgical removal,” as an alternative to a systemic therapy like vismodegib (Erivedge).
Dr. Goldstein said the strengths of the study were in the variety of tumors, close follow-up with histologic evaluation and safety signals. In terms of limitations, she said whether there were any cases of Gorlin syndrome was not clear. In addition, at least 30% of BCCs have a mixed tumor type on Mohs surgery that differs from the original biopsy, and “there was no mention if the residual tumor remained with the same histology,” she said.
In the future, a large, randomized trial is warranted to stratify for Gorlin syndrome, patients who are immunosuppressed, and additional tumor types that were underrepresented in this study, such as micronodular tumors, Dr. Goldstein said. Future studies also should examine how remetinostat impacts BCC in facial areas, the effect of multiple applications, and how the therapy performs as an adjunctive treatment before surgery.
This study was funded by Medivir, the Damon Runyon Foundation, National Cancer Institute, an American Skin Association Hambrick Medical Student grant, and Stanford Medical Scholars. Dr. Kilgour and Dr. Goldstein reported no relevant financial disclosures.
FROM SID 2021
Cross-sectional study finds chronic skin conditions have highest opioid prescribing rates
at dermatology visits.
“Overall, opioid prescribing rates among dermatologists were low. However, dermatologists should remain aware of risk factors for long-term opioid use and consider using nonnarcotic or nonpharmacologic interventions when possible,” Sarah P. Pourali, a medical student at Vanderbilt University, Nashville, said at the annual meeting of the Society for Investigative Dermatology, where she presented the results.
Ms. Pourali said that although Mohs surgery and dermatologic procedures are the focus of “much of the literature” concerning opioid use in dermatology, there are limited data on medication prescribing patterns for other skin conditions treated by dermatologists.
She and her colleagues performed a cross-sectional study using data from the National Ambulatory Medical Care Survey (NAMCS) from 2009 to 2016 on 288,462,610 weighted dermatology visits. The researchers used International Classification of Diseases, Ninth Revision (ICD-9) and ICD-10 codes to identify dermatologic diseases. They also identified and grouped oral pain medication into the following categories: opiate analgesics, nonsteroidal anti-inflammatory drugs, acetaminophen, and gabapentin. A linear regression analysis was used to evaluate pain medicine prescribing each year, and the researchers used a logistic regression analysis to explore how opiate prescriptions were connected to patient clinical characteristics. The analysis was adjusted for age, gender, race, ethnicity, and region.
Overall, most dermatology visits were for patients older than 65 years (36.2%) and 45-64 years old (32.1%). Over half of the dermatologist visits were for women (56.4%) and most (92.2%) visits were for patients who were White (5.1 % were for patients who were Black); most were non-Hispanic or Latino (93.5%). Most dermatology visits were in the South (35.4%) and West (25.2%), followed by the Northeast (21.9%) and Midwest (17.5%).
Opioids were prescribed in 1.3% of the visits, Ms. Pourali said. In addition, 4.7% of visits included an NSAID prescription, 0.7% an acetaminophen prescription, and 0.6% a gabapentin prescription.
Dermatologic procedure visits accounted for 43.1% of opioid prescriptions, she noted. The most common skin conditions for which opioids were prescribed included vitiligo (10.3%), hemangioma (3.8%), pemphigus (3.6%), atopic dermatitis (3.4%), and psoriasis (2.5%).
Although patients older than 65 years accounted for 36.2% of visits to dermatologists, 58.5% of opioids prescribed by dermatologists were for patients in this age group. “We hypothesize that this may be due to a higher proportion of older patients requiring skin cancer surgeries where a lot of opioids are prescribed within dermatology,” Ms. Pourali said.
The highest population-adjusted prescription rates for opiates were in the Northeast and Western regions of the United States, which “partially corroborates” previous studies that have found “higher rates of opioid prescribing in the southern and western U.S.,” she noted.
When evaluating risk-factors for long-term opiate use, Ms. Pourali and colleagues found opioids were also prescribed in 13.2% of visits where a benzodiazepine was prescribed (adjusted odds ratio, 8.17; 95% confidence interval, 5.3-12.7), 8.4% of visits where the patient had a substance abuse disorder (adjusted OR, 9.40; 95% CI, 2.0-44.4), 5.2% of visits with a patient who had depression (adjusted OR, 3.28; 95% CI, 2.0-5.4), and 2.4% of visits with a patient who used tobacco (adjusted OR, 1.09; 95% CI, 1.0-1.1).
Consider nonopioid postoperative pain management options
In an interview, Sailesh Konda, MD, associate clinical professor of dermatology and director of Mohs surgery and surgical dermatology at the University of Florida, Gainesville, who was not involved with the research, noted the finding in the study that vitiligo, hemangioma, pemphigus, AD, and psoriasis were diagnoses with the highest rates of opioid prescription was surprising. “In general, these are conditions that are not routinely managed with opioids,” he said.
NAMCS contains a primary diagnosis field and space for four additional diagnoses such as chronic conditions, as well as thirty fields for medications. “If an opioid was prescribed at a visit, it could have been prescribed for any of the diagnoses related to the visit,” Dr. Konda said. “Additionally, for those opioid prescriptions associated with dermatologic procedures, it would have been helpful to have a breakdown of the specific procedures.”
Dr. Konda compared these results to a recent study of opioid prescribing patterns in the dermatology Medicare population, which found that 93.9% of the top 1% of opioid prescribers were dermatologists working in a surgical practice.
He said that recommendations for opioid prescribing should be developed for general dermatology as they have been for Mohs surgery and dermatologic surgery. For dermatologists currently prescribing opioids, he recommended monitoring prescribing patterns and to “consider nonopioid interventions, such as acetaminophen plus ibuprofen, which has been found to effectively control postoperative pain with fewer complications.”
Ms. Pourali reports no relevant financial disclosures. Her coauthors included the principal investigator, April Armstrong, MD, MPH, professor of dermatology, University of Southern California, Los Angeles. Dr. Konda reports no relevant financial disclosures.
at dermatology visits.
“Overall, opioid prescribing rates among dermatologists were low. However, dermatologists should remain aware of risk factors for long-term opioid use and consider using nonnarcotic or nonpharmacologic interventions when possible,” Sarah P. Pourali, a medical student at Vanderbilt University, Nashville, said at the annual meeting of the Society for Investigative Dermatology, where she presented the results.
Ms. Pourali said that although Mohs surgery and dermatologic procedures are the focus of “much of the literature” concerning opioid use in dermatology, there are limited data on medication prescribing patterns for other skin conditions treated by dermatologists.
She and her colleagues performed a cross-sectional study using data from the National Ambulatory Medical Care Survey (NAMCS) from 2009 to 2016 on 288,462,610 weighted dermatology visits. The researchers used International Classification of Diseases, Ninth Revision (ICD-9) and ICD-10 codes to identify dermatologic diseases. They also identified and grouped oral pain medication into the following categories: opiate analgesics, nonsteroidal anti-inflammatory drugs, acetaminophen, and gabapentin. A linear regression analysis was used to evaluate pain medicine prescribing each year, and the researchers used a logistic regression analysis to explore how opiate prescriptions were connected to patient clinical characteristics. The analysis was adjusted for age, gender, race, ethnicity, and region.
Overall, most dermatology visits were for patients older than 65 years (36.2%) and 45-64 years old (32.1%). Over half of the dermatologist visits were for women (56.4%) and most (92.2%) visits were for patients who were White (5.1 % were for patients who were Black); most were non-Hispanic or Latino (93.5%). Most dermatology visits were in the South (35.4%) and West (25.2%), followed by the Northeast (21.9%) and Midwest (17.5%).
Opioids were prescribed in 1.3% of the visits, Ms. Pourali said. In addition, 4.7% of visits included an NSAID prescription, 0.7% an acetaminophen prescription, and 0.6% a gabapentin prescription.
Dermatologic procedure visits accounted for 43.1% of opioid prescriptions, she noted. The most common skin conditions for which opioids were prescribed included vitiligo (10.3%), hemangioma (3.8%), pemphigus (3.6%), atopic dermatitis (3.4%), and psoriasis (2.5%).
Although patients older than 65 years accounted for 36.2% of visits to dermatologists, 58.5% of opioids prescribed by dermatologists were for patients in this age group. “We hypothesize that this may be due to a higher proportion of older patients requiring skin cancer surgeries where a lot of opioids are prescribed within dermatology,” Ms. Pourali said.
The highest population-adjusted prescription rates for opiates were in the Northeast and Western regions of the United States, which “partially corroborates” previous studies that have found “higher rates of opioid prescribing in the southern and western U.S.,” she noted.
When evaluating risk-factors for long-term opiate use, Ms. Pourali and colleagues found opioids were also prescribed in 13.2% of visits where a benzodiazepine was prescribed (adjusted odds ratio, 8.17; 95% confidence interval, 5.3-12.7), 8.4% of visits where the patient had a substance abuse disorder (adjusted OR, 9.40; 95% CI, 2.0-44.4), 5.2% of visits with a patient who had depression (adjusted OR, 3.28; 95% CI, 2.0-5.4), and 2.4% of visits with a patient who used tobacco (adjusted OR, 1.09; 95% CI, 1.0-1.1).
Consider nonopioid postoperative pain management options
In an interview, Sailesh Konda, MD, associate clinical professor of dermatology and director of Mohs surgery and surgical dermatology at the University of Florida, Gainesville, who was not involved with the research, noted the finding in the study that vitiligo, hemangioma, pemphigus, AD, and psoriasis were diagnoses with the highest rates of opioid prescription was surprising. “In general, these are conditions that are not routinely managed with opioids,” he said.
NAMCS contains a primary diagnosis field and space for four additional diagnoses such as chronic conditions, as well as thirty fields for medications. “If an opioid was prescribed at a visit, it could have been prescribed for any of the diagnoses related to the visit,” Dr. Konda said. “Additionally, for those opioid prescriptions associated with dermatologic procedures, it would have been helpful to have a breakdown of the specific procedures.”
Dr. Konda compared these results to a recent study of opioid prescribing patterns in the dermatology Medicare population, which found that 93.9% of the top 1% of opioid prescribers were dermatologists working in a surgical practice.
He said that recommendations for opioid prescribing should be developed for general dermatology as they have been for Mohs surgery and dermatologic surgery. For dermatologists currently prescribing opioids, he recommended monitoring prescribing patterns and to “consider nonopioid interventions, such as acetaminophen plus ibuprofen, which has been found to effectively control postoperative pain with fewer complications.”
Ms. Pourali reports no relevant financial disclosures. Her coauthors included the principal investigator, April Armstrong, MD, MPH, professor of dermatology, University of Southern California, Los Angeles. Dr. Konda reports no relevant financial disclosures.
at dermatology visits.
“Overall, opioid prescribing rates among dermatologists were low. However, dermatologists should remain aware of risk factors for long-term opioid use and consider using nonnarcotic or nonpharmacologic interventions when possible,” Sarah P. Pourali, a medical student at Vanderbilt University, Nashville, said at the annual meeting of the Society for Investigative Dermatology, where she presented the results.
Ms. Pourali said that although Mohs surgery and dermatologic procedures are the focus of “much of the literature” concerning opioid use in dermatology, there are limited data on medication prescribing patterns for other skin conditions treated by dermatologists.
She and her colleagues performed a cross-sectional study using data from the National Ambulatory Medical Care Survey (NAMCS) from 2009 to 2016 on 288,462,610 weighted dermatology visits. The researchers used International Classification of Diseases, Ninth Revision (ICD-9) and ICD-10 codes to identify dermatologic diseases. They also identified and grouped oral pain medication into the following categories: opiate analgesics, nonsteroidal anti-inflammatory drugs, acetaminophen, and gabapentin. A linear regression analysis was used to evaluate pain medicine prescribing each year, and the researchers used a logistic regression analysis to explore how opiate prescriptions were connected to patient clinical characteristics. The analysis was adjusted for age, gender, race, ethnicity, and region.
Overall, most dermatology visits were for patients older than 65 years (36.2%) and 45-64 years old (32.1%). Over half of the dermatologist visits were for women (56.4%) and most (92.2%) visits were for patients who were White (5.1 % were for patients who were Black); most were non-Hispanic or Latino (93.5%). Most dermatology visits were in the South (35.4%) and West (25.2%), followed by the Northeast (21.9%) and Midwest (17.5%).
Opioids were prescribed in 1.3% of the visits, Ms. Pourali said. In addition, 4.7% of visits included an NSAID prescription, 0.7% an acetaminophen prescription, and 0.6% a gabapentin prescription.
Dermatologic procedure visits accounted for 43.1% of opioid prescriptions, she noted. The most common skin conditions for which opioids were prescribed included vitiligo (10.3%), hemangioma (3.8%), pemphigus (3.6%), atopic dermatitis (3.4%), and psoriasis (2.5%).
Although patients older than 65 years accounted for 36.2% of visits to dermatologists, 58.5% of opioids prescribed by dermatologists were for patients in this age group. “We hypothesize that this may be due to a higher proportion of older patients requiring skin cancer surgeries where a lot of opioids are prescribed within dermatology,” Ms. Pourali said.
The highest population-adjusted prescription rates for opiates were in the Northeast and Western regions of the United States, which “partially corroborates” previous studies that have found “higher rates of opioid prescribing in the southern and western U.S.,” she noted.
When evaluating risk-factors for long-term opiate use, Ms. Pourali and colleagues found opioids were also prescribed in 13.2% of visits where a benzodiazepine was prescribed (adjusted odds ratio, 8.17; 95% confidence interval, 5.3-12.7), 8.4% of visits where the patient had a substance abuse disorder (adjusted OR, 9.40; 95% CI, 2.0-44.4), 5.2% of visits with a patient who had depression (adjusted OR, 3.28; 95% CI, 2.0-5.4), and 2.4% of visits with a patient who used tobacco (adjusted OR, 1.09; 95% CI, 1.0-1.1).
Consider nonopioid postoperative pain management options
In an interview, Sailesh Konda, MD, associate clinical professor of dermatology and director of Mohs surgery and surgical dermatology at the University of Florida, Gainesville, who was not involved with the research, noted the finding in the study that vitiligo, hemangioma, pemphigus, AD, and psoriasis were diagnoses with the highest rates of opioid prescription was surprising. “In general, these are conditions that are not routinely managed with opioids,” he said.
NAMCS contains a primary diagnosis field and space for four additional diagnoses such as chronic conditions, as well as thirty fields for medications. “If an opioid was prescribed at a visit, it could have been prescribed for any of the diagnoses related to the visit,” Dr. Konda said. “Additionally, for those opioid prescriptions associated with dermatologic procedures, it would have been helpful to have a breakdown of the specific procedures.”
Dr. Konda compared these results to a recent study of opioid prescribing patterns in the dermatology Medicare population, which found that 93.9% of the top 1% of opioid prescribers were dermatologists working in a surgical practice.
He said that recommendations for opioid prescribing should be developed for general dermatology as they have been for Mohs surgery and dermatologic surgery. For dermatologists currently prescribing opioids, he recommended monitoring prescribing patterns and to “consider nonopioid interventions, such as acetaminophen plus ibuprofen, which has been found to effectively control postoperative pain with fewer complications.”
Ms. Pourali reports no relevant financial disclosures. Her coauthors included the principal investigator, April Armstrong, MD, MPH, professor of dermatology, University of Southern California, Los Angeles. Dr. Konda reports no relevant financial disclosures.
FROM SID 2021