Over the past 20 years, patients with asthma and chronic obstructive pulmonary disease (COPD) have seen next to no improvement in problems of delayed care because of cost or unaffordable medications, despite wider insurance coverage since the passage of the Affordable Care Act, a new analysis shows.

The long-view analysis illuminates the ongoing problem for people with these chronic diseases despite health care legislation that was considered historic.

“That long-term scope puts recent improvements in better context – whereas we have made improvements in coverage in recent years due to the Affordable Care Act, the longer-term picture is that people with asthma and COPD are struggling to obtain needed medical care and medications despite a substantial reduction in the uninsurance rate,” said Adam Gaffney, MD, MPH, assistant professor of medicine at Harvard Medical School, Boston who authored the paper with David Himmelstein, MD, professor of public health at City University of New York–Hunter College. The findings were published in Chest.

Researchers examined data from 1997 to 2018 for 76,843 adults with asthma and 30,548 adults with COPD, from the National Health Interview Survey, an annual survey by the Centers for Disease Control that is based on in-person interviews and health questionnaires completed by an adult in each family.
 

Insurance coverage up, patients losing ground

During 1997 and 2018, there was an overall 9.3% decrease in the rate of adults with asthma who were uninsured, a significant improvement (P < .001). Between the pre- and post-ACA years, there was modest improvement in those putting off care because of cost, a drop of 3.8%, or going without prescriptions, a drop of 4.0%. But those improvements didn’t correspond to the 7.2% drop in the uninsured rate after the AC , contributing to the finding that there was no significant improvement over the 20 years.

For adults with COPD, it was a slightly different story. Over those 2 decades, the uninsured rate dropped by 9.5%. But the number of patients foregoing care due to cost actually rose by 3.4%, which wasn’t statistically significant, but the rate of those unable to afford needed medications rose significantly by 7.8%.

Researchers found there was improvement between the pre- and post-ACA years among COPD patients putting off care and going without medications (decreases of 6.9% and 4.5%, respectively). That adhered fairly closely with the improvement in the uninsured rate, which fell by 7.1%. But over the 20-year study period, the percentage of those needing medications they couldn’t afford increased significantly by 7.8%. The rate of those delaying or foregoing care also increased, though this amount was not statistically significant.

After the ACA was created, Blacks and Hispanics with asthma had greater improvement in obtaining insurance, compared with other racial and ethnic groups. But over the 20 years, like all racial and ethnic groups, they saw no statistically significant improvement in rates of “inadequate coverage,” defined in this study as either being uninsured, having to delay care because of cost, or being unable to afford needed medications.

For those with COPD, only Whites had statistically significant improvement in the number of patients with inadequate coverage after the ACA, researchers found.

So despite obtaining insurance, patients lost ground in managing their disease because of the growing cost of care and medication.

“Medication affordability has actually worsened for those with COPD – a worrisome development given that medication nonadherence worsens outcomes for these vulnerable patients,” Dr. Gaffney said. “Policy makers should return to the issue of national health care reform. Both uninsurance and underinsurance undermines pulmonologists’ ability to care for their patients with chronic disease. A health care system without financial barriers, in contrast, might well improve these patients’ outcomes, and advance health equity.”
 

Insurance is no guarantee to access

Daniel Ouellette, MD, FCCP, a pulmonary and critical care specialist at Henry Ford Health System in Detroit, said it’s not surprising that access to care remains a problem despite the Affordable Care Act.

“It covers the hospitalizations and ER visits – patients in this segment of society were getting cared for there anyway,” he said. “And what the ACA didn’t always do was provide adequate prescription coverage or cover these outpatient gaps. So even though the patients have the ACA they still have unaffordable prescriptions, they still can’t buy them, and they still can’t pay for their outpatient clinic if they have a $500 or $1,000 deductible.” These patients also continue to struggle with more fundamental issues that affect access to care, such as lack of transportation and poor health literacy.

At Henry Ford, pharmacists work with patients to identify medications covered by their insurance and work to find discounts and coupons, he said. As for the ACA, “it’s a good first start, but we really need to identify what its limitations are.” Locally driven, less expensive solutions might be a better way forward than costly federal initiatives.

Brandon M. Seay, MD, a pediatric pulmonologist and sleep specialist at Children’s Healthcare of Atlanta, said the findings dovetail with what he has seen in the pediatric population.

“From my experience, the ACA has helped patients get their foot in the door and has helped patients decrease the possibility of serious financial burden in emergency situations, but the ability to afford medications has not changed very much,” he said. When patients struggle with sufficient prescription coverage, he helps patients fight for coverage and connects them with prescription assistance programs such as GoodRx.

“Instead of focusing on the access of insurance to patients, the goal of the system should be to make care as affordable as possible,” Dr. Seay said. “Access does not meet the needs of a patient if they cannot afford what they have access to. Transition to a nationalized health system where there is no question of access could help to drive down prescription drug prices by allowing the government to negotiate with pharmaceutical companies more adequately by removing the ‘middle man’ of the private insurance industry.”

The investigators reported no financial conflicts. Dr. Ouellette and Dr. Seay reported no financial conflicts.

Over the past 20 years, patients with asthma and chronic obstructive pulmonary disease (COPD) have seen next to no improvement in problems of delayed care because of cost or unaffordable medications, despite wider insurance coverage since the passage of the Affordable Care Act, a new analysis shows.

The long-view analysis illuminates the ongoing problem for people with these chronic diseases despite health care legislation that was considered historic.

“That long-term scope puts recent improvements in better context – whereas we have made improvements in coverage in recent years due to the Affordable Care Act, the longer-term picture is that people with asthma and COPD are struggling to obtain needed medical care and medications despite a substantial reduction in the uninsurance rate,” said Adam Gaffney, MD, MPH, assistant professor of medicine at Harvard Medical School, Boston who authored the paper with David Himmelstein, MD, professor of public health at City University of New York–Hunter College. The findings were published in Chest.

Researchers examined data from 1997 to 2018 for 76,843 adults with asthma and 30,548 adults with COPD, from the National Health Interview Survey, an annual survey by the Centers for Disease Control that is based on in-person interviews and health questionnaires completed by an adult in each family.
 

Insurance coverage up, patients losing ground

During 1997 and 2018, there was an overall 9.3% decrease in the rate of adults with asthma who were uninsured, a significant improvement (P < .001). Between the pre- and post-ACA years, there was modest improvement in those putting off care because of cost, a drop of 3.8%, or going without prescriptions, a drop of 4.0%. But those improvements didn’t correspond to the 7.2% drop in the uninsured rate after the AC , contributing to the finding that there was no significant improvement over the 20 years.

For adults with COPD, it was a slightly different story. Over those 2 decades, the uninsured rate dropped by 9.5%. But the number of patients foregoing care due to cost actually rose by 3.4%, which wasn’t statistically significant, but the rate of those unable to afford needed medications rose significantly by 7.8%.

Researchers found there was improvement between the pre- and post-ACA years among COPD patients putting off care and going without medications (decreases of 6.9% and 4.5%, respectively). That adhered fairly closely with the improvement in the uninsured rate, which fell by 7.1%. But over the 20-year study period, the percentage of those needing medications they couldn’t afford increased significantly by 7.8%. The rate of those delaying or foregoing care also increased, though this amount was not statistically significant.

After the ACA was created, Blacks and Hispanics with asthma had greater improvement in obtaining insurance, compared with other racial and ethnic groups. But over the 20 years, like all racial and ethnic groups, they saw no statistically significant improvement in rates of “inadequate coverage,” defined in this study as either being uninsured, having to delay care because of cost, or being unable to afford needed medications.

For those with COPD, only Whites had statistically significant improvement in the number of patients with inadequate coverage after the ACA, researchers found.

So despite obtaining insurance, patients lost ground in managing their disease because of the growing cost of care and medication.

“Medication affordability has actually worsened for those with COPD – a worrisome development given that medication nonadherence worsens outcomes for these vulnerable patients,” Dr. Gaffney said. “Policy makers should return to the issue of national health care reform. Both uninsurance and underinsurance undermines pulmonologists’ ability to care for their patients with chronic disease. A health care system without financial barriers, in contrast, might well improve these patients’ outcomes, and advance health equity.”
 

Insurance is no guarantee to access

Daniel Ouellette, MD, FCCP, a pulmonary and critical care specialist at Henry Ford Health System in Detroit, said it’s not surprising that access to care remains a problem despite the Affordable Care Act.

“It covers the hospitalizations and ER visits – patients in this segment of society were getting cared for there anyway,” he said. “And what the ACA didn’t always do was provide adequate prescription coverage or cover these outpatient gaps. So even though the patients have the ACA they still have unaffordable prescriptions, they still can’t buy them, and they still can’t pay for their outpatient clinic if they have a $500 or $1,000 deductible.” These patients also continue to struggle with more fundamental issues that affect access to care, such as lack of transportation and poor health literacy.

At Henry Ford, pharmacists work with patients to identify medications covered by their insurance and work to find discounts and coupons, he said. As for the ACA, “it’s a good first start, but we really need to identify what its limitations are.” Locally driven, less expensive solutions might be a better way forward than costly federal initiatives.

Brandon M. Seay, MD, a pediatric pulmonologist and sleep specialist at Children’s Healthcare of Atlanta, said the findings dovetail with what he has seen in the pediatric population.

“From my experience, the ACA has helped patients get their foot in the door and has helped patients decrease the possibility of serious financial burden in emergency situations, but the ability to afford medications has not changed very much,” he said. When patients struggle with sufficient prescription coverage, he helps patients fight for coverage and connects them with prescription assistance programs such as GoodRx.

“Instead of focusing on the access of insurance to patients, the goal of the system should be to make care as affordable as possible,” Dr. Seay said. “Access does not meet the needs of a patient if they cannot afford what they have access to. Transition to a nationalized health system where there is no question of access could help to drive down prescription drug prices by allowing the government to negotiate with pharmaceutical companies more adequately by removing the ‘middle man’ of the private insurance industry.”

The investigators reported no financial conflicts. Dr. Ouellette and Dr. Seay reported no financial conflicts.

Over the past 20 years, patients with asthma and chronic obstructive pulmonary disease (COPD) have seen next to no improvement in problems of delayed care because of cost or unaffordable medications, despite wider insurance coverage since the passage of the Affordable Care Act, a new analysis shows.

The long-view analysis illuminates the ongoing problem for people with these chronic diseases despite health care legislation that was considered historic.

“That long-term scope puts recent improvements in better context – whereas we have made improvements in coverage in recent years due to the Affordable Care Act, the longer-term picture is that people with asthma and COPD are struggling to obtain needed medical care and medications despite a substantial reduction in the uninsurance rate,” said Adam Gaffney, MD, MPH, assistant professor of medicine at Harvard Medical School, Boston who authored the paper with David Himmelstein, MD, professor of public health at City University of New York–Hunter College. The findings were published in Chest.

Researchers examined data from 1997 to 2018 for 76,843 adults with asthma and 30,548 adults with COPD, from the National Health Interview Survey, an annual survey by the Centers for Disease Control that is based on in-person interviews and health questionnaires completed by an adult in each family.
 

Insurance coverage up, patients losing ground

During 1997 and 2018, there was an overall 9.3% decrease in the rate of adults with asthma who were uninsured, a significant improvement (P < .001). Between the pre- and post-ACA years, there was modest improvement in those putting off care because of cost, a drop of 3.8%, or going without prescriptions, a drop of 4.0%. But those improvements didn’t correspond to the 7.2% drop in the uninsured rate after the AC , contributing to the finding that there was no significant improvement over the 20 years.

For adults with COPD, it was a slightly different story. Over those 2 decades, the uninsured rate dropped by 9.5%. But the number of patients foregoing care due to cost actually rose by 3.4%, which wasn’t statistically significant, but the rate of those unable to afford needed medications rose significantly by 7.8%.

Researchers found there was improvement between the pre- and post-ACA years among COPD patients putting off care and going without medications (decreases of 6.9% and 4.5%, respectively). That adhered fairly closely with the improvement in the uninsured rate, which fell by 7.1%. But over the 20-year study period, the percentage of those needing medications they couldn’t afford increased significantly by 7.8%. The rate of those delaying or foregoing care also increased, though this amount was not statistically significant.

After the ACA was created, Blacks and Hispanics with asthma had greater improvement in obtaining insurance, compared with other racial and ethnic groups. But over the 20 years, like all racial and ethnic groups, they saw no statistically significant improvement in rates of “inadequate coverage,” defined in this study as either being uninsured, having to delay care because of cost, or being unable to afford needed medications.

For those with COPD, only Whites had statistically significant improvement in the number of patients with inadequate coverage after the ACA, researchers found.

So despite obtaining insurance, patients lost ground in managing their disease because of the growing cost of care and medication.

“Medication affordability has actually worsened for those with COPD – a worrisome development given that medication nonadherence worsens outcomes for these vulnerable patients,” Dr. Gaffney said. “Policy makers should return to the issue of national health care reform. Both uninsurance and underinsurance undermines pulmonologists’ ability to care for their patients with chronic disease. A health care system without financial barriers, in contrast, might well improve these patients’ outcomes, and advance health equity.”
 

Insurance is no guarantee to access

Daniel Ouellette, MD, FCCP, a pulmonary and critical care specialist at Henry Ford Health System in Detroit, said it’s not surprising that access to care remains a problem despite the Affordable Care Act.

“It covers the hospitalizations and ER visits – patients in this segment of society were getting cared for there anyway,” he said. “And what the ACA didn’t always do was provide adequate prescription coverage or cover these outpatient gaps. So even though the patients have the ACA they still have unaffordable prescriptions, they still can’t buy them, and they still can’t pay for their outpatient clinic if they have a $500 or $1,000 deductible.” These patients also continue to struggle with more fundamental issues that affect access to care, such as lack of transportation and poor health literacy.

At Henry Ford, pharmacists work with patients to identify medications covered by their insurance and work to find discounts and coupons, he said. As for the ACA, “it’s a good first start, but we really need to identify what its limitations are.” Locally driven, less expensive solutions might be a better way forward than costly federal initiatives.

Brandon M. Seay, MD, a pediatric pulmonologist and sleep specialist at Children’s Healthcare of Atlanta, said the findings dovetail with what he has seen in the pediatric population.

“From my experience, the ACA has helped patients get their foot in the door and has helped patients decrease the possibility of serious financial burden in emergency situations, but the ability to afford medications has not changed very much,” he said. When patients struggle with sufficient prescription coverage, he helps patients fight for coverage and connects them with prescription assistance programs such as GoodRx.

“Instead of focusing on the access of insurance to patients, the goal of the system should be to make care as affordable as possible,” Dr. Seay said. “Access does not meet the needs of a patient if they cannot afford what they have access to. Transition to a nationalized health system where there is no question of access could help to drive down prescription drug prices by allowing the government to negotiate with pharmaceutical companies more adequately by removing the ‘middle man’ of the private insurance industry.”

The investigators reported no financial conflicts. Dr. Ouellette and Dr. Seay reported no financial conflicts.

Dried blood spot testing showed sensitivity comparable to saliva as a screening method for congenital cytomegalovirus infection in newborns, based on data from more than 12,000 newborns.

Congenital cytomegalovirus (cCMV) is a common congenital virus in the United States, but remains underrecognized, wrote Sheila C. Dollard, PhD, of the Centers for Disease Control and Prevention in Atlanta, and colleagues.

“Given the burden associated with cCMV and the proven benefits of treatment and early intervention for some affected infants, there has been growing interest in universal newborn screening,” but an ideal screening strategy has yet to be determined, they said.

In a population-based cohort study published in JAMA Pediatrics, the researchers screened 12,554 newborns in Minnesota, including 56 with confirmed CMV infection. The newborns were screened for cCMV via dried blood spots (DBS) and saliva collected 1-2 days after birth. The DBS were tested for CMV DNA via polymerase chain reaction (PCR) at the University of Minnesota (UMN) and the CDC.

The overall sensitivity rate was 85.7% for a combination of laboratory results from the UMN and the CDC, which had separate sensitivities of 73.2% and 76.8%, respectively.

The specificity of the combined results was 100.0% (100% from both UMN and CDC), the combined positive predictive value was 98.0% (100.0% from UMN, 97.7% from CDC), and the combined negative predictive value was 99.9% (99.9% from both UMN and CDC).

By comparison, saliva swab test results showed sensitivity of 92.9%, specificity of 99.9%, positive predictive value of 86.7%, and negative predictive value of 100.0%.

The study findings were limited by several factors including the false-positive and false-negative results from saliva screening. Overall, the false-positive rate was 0.06%, which is comparable to rates from other screening techniques, the researchers said. “The recent Food and Drug Administration approval of a point-of-care neonatal saliva CMV test (Meridian Bioscience), underscores the importance of further clarifying the role of false-positive saliva CMV test results and underscores the requirement for urine confirmation for diagnosis of cCMV,” they added.

However, the study findings support the acceptability and feasibility of cCMV screening, as parents reported generally positive attitudes about the process, the researchers said.

The study is ongoing, and designed to follow infants with confirmed cCMV for up to age 4 years to assess clinical outcomes, they added. “Diagnostic methods are always improving, and therefore, our results show the potential of DBS to provide low-cost CMV screening with smooth integration of sample collection, laboratory testing, and follow-up,” they concluded.
 

Findings lay foundation for widespread use

“By using enhanced PCR methods, Dollard et al. have rekindled the hope that NBDBS [newborn dried blood spots] testing may be a viable method for large-scale, universal newborn screening for congenital CMV,” Gail J. Demmler-Harrison, MD, of Texas Children’s Hospital, Houston, wrote in an accompanying editorial. Congenital CMV is a common infection, but accurate prevalence remains uncertain because not all newborns are tested, she noted. Detection of CMV currently may involve urine, saliva, and blood, but challenges to the use of these methods include “a variety of constantly evolving DNA detection methods,” she said.

Although urine and saliva samples have been proposed for universal screening, they would require the creation of new sample collection and testing programs. “The routine of collecting the NBDBS samples on all newborns and the logistics of routing them to central laboratories and then reporting results to caregivers is already in place and are strengths of NBDBS samples for universal newborn screening,” but had been limited by a less sensitive platform than urine or saliva, said Dr. Demmler-Harrison.

“The results in the study by Dollard et al. may be a total game changer for the NBDBS proponents,” she emphasized. “Furthermore, scientists who have adapted even more sensitive DNA detection assays, such as the loop-mediated isothermal assay for detection of DNA in clinical samples from newborns, may be able to adapt loop-mediated isothermal assay methodology to detect CMV DNA in NBDBS,” she added.

“By adapting the collection methods, by using optimal filter paper to enhance DNA adherence, by improving DNA elution procedures, and by developing novel amplification and detection methods, NBDBS may soon meet the challenge and reach the sensitivity and specificity necessary for universal screening for congenital CMV,” she concluded.

The study was supported by the CDC, the Minnesota Department of Health, the National Vaccine Program Office (U.S. federal government), and the University of South Carolina Disability Research and Dissemination Center.

Dr. Dollard and Dr. Demmler-Harrison had no financial conflicts to disclose.

Dried blood spot testing showed sensitivity comparable to saliva as a screening method for congenital cytomegalovirus infection in newborns, based on data from more than 12,000 newborns.

Congenital cytomegalovirus (cCMV) is a common congenital virus in the United States, but remains underrecognized, wrote Sheila C. Dollard, PhD, of the Centers for Disease Control and Prevention in Atlanta, and colleagues.

“Given the burden associated with cCMV and the proven benefits of treatment and early intervention for some affected infants, there has been growing interest in universal newborn screening,” but an ideal screening strategy has yet to be determined, they said.

In a population-based cohort study published in JAMA Pediatrics, the researchers screened 12,554 newborns in Minnesota, including 56 with confirmed CMV infection. The newborns were screened for cCMV via dried blood spots (DBS) and saliva collected 1-2 days after birth. The DBS were tested for CMV DNA via polymerase chain reaction (PCR) at the University of Minnesota (UMN) and the CDC.

The overall sensitivity rate was 85.7% for a combination of laboratory results from the UMN and the CDC, which had separate sensitivities of 73.2% and 76.8%, respectively.

The specificity of the combined results was 100.0% (100% from both UMN and CDC), the combined positive predictive value was 98.0% (100.0% from UMN, 97.7% from CDC), and the combined negative predictive value was 99.9% (99.9% from both UMN and CDC).

By comparison, saliva swab test results showed sensitivity of 92.9%, specificity of 99.9%, positive predictive value of 86.7%, and negative predictive value of 100.0%.

The study findings were limited by several factors including the false-positive and false-negative results from saliva screening. Overall, the false-positive rate was 0.06%, which is comparable to rates from other screening techniques, the researchers said. “The recent Food and Drug Administration approval of a point-of-care neonatal saliva CMV test (Meridian Bioscience), underscores the importance of further clarifying the role of false-positive saliva CMV test results and underscores the requirement for urine confirmation for diagnosis of cCMV,” they added.

However, the study findings support the acceptability and feasibility of cCMV screening, as parents reported generally positive attitudes about the process, the researchers said.

The study is ongoing, and designed to follow infants with confirmed cCMV for up to age 4 years to assess clinical outcomes, they added. “Diagnostic methods are always improving, and therefore, our results show the potential of DBS to provide low-cost CMV screening with smooth integration of sample collection, laboratory testing, and follow-up,” they concluded.
 

Findings lay foundation for widespread use

“By using enhanced PCR methods, Dollard et al. have rekindled the hope that NBDBS [newborn dried blood spots] testing may be a viable method for large-scale, universal newborn screening for congenital CMV,” Gail J. Demmler-Harrison, MD, of Texas Children’s Hospital, Houston, wrote in an accompanying editorial. Congenital CMV is a common infection, but accurate prevalence remains uncertain because not all newborns are tested, she noted. Detection of CMV currently may involve urine, saliva, and blood, but challenges to the use of these methods include “a variety of constantly evolving DNA detection methods,” she said.

Although urine and saliva samples have been proposed for universal screening, they would require the creation of new sample collection and testing programs. “The routine of collecting the NBDBS samples on all newborns and the logistics of routing them to central laboratories and then reporting results to caregivers is already in place and are strengths of NBDBS samples for universal newborn screening,” but had been limited by a less sensitive platform than urine or saliva, said Dr. Demmler-Harrison.

“The results in the study by Dollard et al. may be a total game changer for the NBDBS proponents,” she emphasized. “Furthermore, scientists who have adapted even more sensitive DNA detection assays, such as the loop-mediated isothermal assay for detection of DNA in clinical samples from newborns, may be able to adapt loop-mediated isothermal assay methodology to detect CMV DNA in NBDBS,” she added.

“By adapting the collection methods, by using optimal filter paper to enhance DNA adherence, by improving DNA elution procedures, and by developing novel amplification and detection methods, NBDBS may soon meet the challenge and reach the sensitivity and specificity necessary for universal screening for congenital CMV,” she concluded.

The study was supported by the CDC, the Minnesota Department of Health, the National Vaccine Program Office (U.S. federal government), and the University of South Carolina Disability Research and Dissemination Center.

Dr. Dollard and Dr. Demmler-Harrison had no financial conflicts to disclose.

Dried blood spot testing showed sensitivity comparable to saliva as a screening method for congenital cytomegalovirus infection in newborns, based on data from more than 12,000 newborns.

Congenital cytomegalovirus (cCMV) is a common congenital virus in the United States, but remains underrecognized, wrote Sheila C. Dollard, PhD, of the Centers for Disease Control and Prevention in Atlanta, and colleagues.

“Given the burden associated with cCMV and the proven benefits of treatment and early intervention for some affected infants, there has been growing interest in universal newborn screening,” but an ideal screening strategy has yet to be determined, they said.

In a population-based cohort study published in JAMA Pediatrics, the researchers screened 12,554 newborns in Minnesota, including 56 with confirmed CMV infection. The newborns were screened for cCMV via dried blood spots (DBS) and saliva collected 1-2 days after birth. The DBS were tested for CMV DNA via polymerase chain reaction (PCR) at the University of Minnesota (UMN) and the CDC.

The overall sensitivity rate was 85.7% for a combination of laboratory results from the UMN and the CDC, which had separate sensitivities of 73.2% and 76.8%, respectively.

The specificity of the combined results was 100.0% (100% from both UMN and CDC), the combined positive predictive value was 98.0% (100.0% from UMN, 97.7% from CDC), and the combined negative predictive value was 99.9% (99.9% from both UMN and CDC).

By comparison, saliva swab test results showed sensitivity of 92.9%, specificity of 99.9%, positive predictive value of 86.7%, and negative predictive value of 100.0%.

The study findings were limited by several factors including the false-positive and false-negative results from saliva screening. Overall, the false-positive rate was 0.06%, which is comparable to rates from other screening techniques, the researchers said. “The recent Food and Drug Administration approval of a point-of-care neonatal saliva CMV test (Meridian Bioscience), underscores the importance of further clarifying the role of false-positive saliva CMV test results and underscores the requirement for urine confirmation for diagnosis of cCMV,” they added.

However, the study findings support the acceptability and feasibility of cCMV screening, as parents reported generally positive attitudes about the process, the researchers said.

The study is ongoing, and designed to follow infants with confirmed cCMV for up to age 4 years to assess clinical outcomes, they added. “Diagnostic methods are always improving, and therefore, our results show the potential of DBS to provide low-cost CMV screening with smooth integration of sample collection, laboratory testing, and follow-up,” they concluded.
 

Findings lay foundation for widespread use

“By using enhanced PCR methods, Dollard et al. have rekindled the hope that NBDBS [newborn dried blood spots] testing may be a viable method for large-scale, universal newborn screening for congenital CMV,” Gail J. Demmler-Harrison, MD, of Texas Children’s Hospital, Houston, wrote in an accompanying editorial. Congenital CMV is a common infection, but accurate prevalence remains uncertain because not all newborns are tested, she noted. Detection of CMV currently may involve urine, saliva, and blood, but challenges to the use of these methods include “a variety of constantly evolving DNA detection methods,” she said.

Although urine and saliva samples have been proposed for universal screening, they would require the creation of new sample collection and testing programs. “The routine of collecting the NBDBS samples on all newborns and the logistics of routing them to central laboratories and then reporting results to caregivers is already in place and are strengths of NBDBS samples for universal newborn screening,” but had been limited by a less sensitive platform than urine or saliva, said Dr. Demmler-Harrison.

“The results in the study by Dollard et al. may be a total game changer for the NBDBS proponents,” she emphasized. “Furthermore, scientists who have adapted even more sensitive DNA detection assays, such as the loop-mediated isothermal assay for detection of DNA in clinical samples from newborns, may be able to adapt loop-mediated isothermal assay methodology to detect CMV DNA in NBDBS,” she added.

“By adapting the collection methods, by using optimal filter paper to enhance DNA adherence, by improving DNA elution procedures, and by developing novel amplification and detection methods, NBDBS may soon meet the challenge and reach the sensitivity and specificity necessary for universal screening for congenital CMV,” she concluded.

The study was supported by the CDC, the Minnesota Department of Health, the National Vaccine Program Office (U.S. federal government), and the University of South Carolina Disability Research and Dissemination Center.

Dr. Dollard and Dr. Demmler-Harrison had no financial conflicts to disclose.

Research has shown that, compared with their urban counterparts, rural cancer patients have higher cancer-related mortality and other negative treatment outcomes.

Among other explanations, the disparity has been attributed to lower education and income levels, medical and behavioral risk factors, differences in health literacy, and lower confidence in the medical system among rural residents (JCO Oncol Pract. 2020 Jul;16(7):422-30).

The COVID-19 and Oncology Patient Experience Consortium

Ms. Daniels explained that the COVID-19 and Oncology Patient Experience (COPES) Consortium was created to investigate various aspects of the patient experience during the pandemic. Three cancer centers – Moffitt Cancer Center, Huntsman Cancer Institute, and the Sylvester Comprehensive Cancer Center – participate in COPES.

At Huntsman, investigators studied social and health behaviors of cancer patients to assess whether there was a difference between those from rural and urban areas. The researchers looked at the impact of the pandemic on psychosocial outcomes, preventive measures patients implemented, and their perceptions of the risk of SARS-CoV-2 infection.

The team’s hypothesis was that rural patients might be more vulnerable than urban patients to the effects of social isolation, emotional distress, and health-adverse behaviors, but the investigators noted that there has been no prior research on the topic.
 

Assessing behaviors, attitudes, and outcomes

Between August and September 2020, the researchers surveyed 1,328 adult cancer patients who had visited Huntsman in the previous 4 years and who were enrolled in Huntsman’s Total Cancer Care or Precision Exercise Prescription studies.

Patients completed questionnaires that encompassed demographic and clinical factors, employment status, health behaviors, and infection preventive measures. Questionnaires were provided in electronic, paper, or phone-based formats. Information regarding age, race, ethnicity, and tumor stage was abstracted from Huntsman’s electronic health record.

Modifications in daily life and social interaction were assessed on a 5-point scale. Changes in exercise habits and alcohol consumption were assessed on a 3-point scale. Infection mitigation measures (the use of face masks and hand sanitizer) and perceptions about the likelihood of SARS-CoV-2 infection were measured.

The rural-urban community area codes system, which classifies U.S. census tracts by measures of population density, urbanization, and daily commuting, was utilized to categorize patients into rural and urban residences.
 

Characteristics of urban and rural cancer patients

There were 997 urban and 331 rural participants. The mean age was 60.1 years in the urban population and 62.6 years in the rural population (P = .01). There were no urban-rural differences in sex, ethnicity, cancer stage, or body mass index.

More urban than rural participants were employed full- or part-time (45% vs. 37%; P = .045). The rural counties had more patients who were not currently employed, primarily due to retirement (77% vs. 69% urban; P < .001).

“No health insurance coverage” was reported by 2% of urban and 4% of rural participants (P = .009), and 85% of all patients reported “good” to “excellent” overall health. Cancer patients in rural counties were significantly more likely to have ever smoked (37% vs. 25% urban; P = .001). In addition, alcohol consumption in the previous year was higher in rural patients. “Every day to less than once monthly” alcohol usage was reported by 44% of urban and 60% of rural patients (P < .001).
 

Changes in daily life and health-related behavior during the pandemic

Urban patients were more likely to report changes in their daily lives due to the pandemic. Specifically, 35% of urban patients and 26% of rural patients said the pandemic had changed their daily life “a lot” (P = .001).

However, there were no major differences between urban and rural patients when it came to changes in social interaction in the past month or feeling lonely in the past month (P = .45 and P = .88, respectively). Similarly, there were no significant differences for changes in alcohol consumption between the groups (P = .90).

Changes in exercise habits due to the pandemic were more common among patients in urban counties (51% vs. 39% rural; P < .001), though similar percentages of patients reported exercising less (44% urban vs. 45% rural) or more frequently (24% urban vs. 20% rural).

In terms of infection mitigation measures, urban patients were more likely to use face masks “very often” (83% vs. 66% rural; P < .001), while hand sanitizer was used “very often” among 66% of urban and 57% of rural participants (P = .05).

Urban participants were more likely than were their rural counterparts to think themselves “somewhat” or “very” likely to develop COVID-19 (22% vs. 14%; P = .04).

It might be short-sighted for oncology and public health specialists to be dismissive of differences in infection mitigation behaviors and perceptions of vulnerability to SARS-CoV-2 infection. Those behaviors and perceptions of risk could lead to lower vaccination rates in rural areas. If that occurs, there would be major negative consequences for the long-term health of rural communities and their medically vulnerable residents.
 

Future directions

Although the first 6 months of the COVID-19 pandemic had disparate effects on cancer patients living in rural and urban counties, the reasons for the disparities are complex and not easily explained by this study.

It is possible that sequential administration of the survey during the pandemic would have uncovered greater variances in attitude and health-related behaviors.

As Ms. Daniels noted, when the survey was performed, Utah had not experienced a high frequency of COVID-19 cases. Furthermore, different levels of restrictions were implemented on a county-by-county basis, potentially influencing patients’ behaviors, psychosocial adjustment, and perceptions of risk.

In addition, there may have been differences in unmeasured endpoints (infection rates, medical care utilization via telemedicine, hospitalization rates, late effects, and mortality) between the urban and rural populations.

As the investigators concluded, further research is needed to better characterize the pandemic’s short- and long-term effects on cancer patients in rural and urban settings and appropriate interventions. Such studies may yield insights into the various facets of the well-documented “rural health gap” in cancer outcomes and interventions that could narrow the gap in spheres beyond the COVID-19 pandemic.

Ms. Daniels reported having no relevant disclosures.
 

Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers, as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.

Research has shown that, compared with their urban counterparts, rural cancer patients have higher cancer-related mortality and other negative treatment outcomes.

Among other explanations, the disparity has been attributed to lower education and income levels, medical and behavioral risk factors, differences in health literacy, and lower confidence in the medical system among rural residents (JCO Oncol Pract. 2020 Jul;16(7):422-30).

The COVID-19 and Oncology Patient Experience Consortium

Ms. Daniels explained that the COVID-19 and Oncology Patient Experience (COPES) Consortium was created to investigate various aspects of the patient experience during the pandemic. Three cancer centers – Moffitt Cancer Center, Huntsman Cancer Institute, and the Sylvester Comprehensive Cancer Center – participate in COPES.

At Huntsman, investigators studied social and health behaviors of cancer patients to assess whether there was a difference between those from rural and urban areas. The researchers looked at the impact of the pandemic on psychosocial outcomes, preventive measures patients implemented, and their perceptions of the risk of SARS-CoV-2 infection.

The team’s hypothesis was that rural patients might be more vulnerable than urban patients to the effects of social isolation, emotional distress, and health-adverse behaviors, but the investigators noted that there has been no prior research on the topic.
 

Assessing behaviors, attitudes, and outcomes

Between August and September 2020, the researchers surveyed 1,328 adult cancer patients who had visited Huntsman in the previous 4 years and who were enrolled in Huntsman’s Total Cancer Care or Precision Exercise Prescription studies.

Patients completed questionnaires that encompassed demographic and clinical factors, employment status, health behaviors, and infection preventive measures. Questionnaires were provided in electronic, paper, or phone-based formats. Information regarding age, race, ethnicity, and tumor stage was abstracted from Huntsman’s electronic health record.

Modifications in daily life and social interaction were assessed on a 5-point scale. Changes in exercise habits and alcohol consumption were assessed on a 3-point scale. Infection mitigation measures (the use of face masks and hand sanitizer) and perceptions about the likelihood of SARS-CoV-2 infection were measured.

The rural-urban community area codes system, which classifies U.S. census tracts by measures of population density, urbanization, and daily commuting, was utilized to categorize patients into rural and urban residences.
 

Characteristics of urban and rural cancer patients

There were 997 urban and 331 rural participants. The mean age was 60.1 years in the urban population and 62.6 years in the rural population (P = .01). There were no urban-rural differences in sex, ethnicity, cancer stage, or body mass index.

More urban than rural participants were employed full- or part-time (45% vs. 37%; P = .045). The rural counties had more patients who were not currently employed, primarily due to retirement (77% vs. 69% urban; P < .001).

“No health insurance coverage” was reported by 2% of urban and 4% of rural participants (P = .009), and 85% of all patients reported “good” to “excellent” overall health. Cancer patients in rural counties were significantly more likely to have ever smoked (37% vs. 25% urban; P = .001). In addition, alcohol consumption in the previous year was higher in rural patients. “Every day to less than once monthly” alcohol usage was reported by 44% of urban and 60% of rural patients (P < .001).
 

Changes in daily life and health-related behavior during the pandemic

Urban patients were more likely to report changes in their daily lives due to the pandemic. Specifically, 35% of urban patients and 26% of rural patients said the pandemic had changed their daily life “a lot” (P = .001).

However, there were no major differences between urban and rural patients when it came to changes in social interaction in the past month or feeling lonely in the past month (P = .45 and P = .88, respectively). Similarly, there were no significant differences for changes in alcohol consumption between the groups (P = .90).

Changes in exercise habits due to the pandemic were more common among patients in urban counties (51% vs. 39% rural; P < .001), though similar percentages of patients reported exercising less (44% urban vs. 45% rural) or more frequently (24% urban vs. 20% rural).

In terms of infection mitigation measures, urban patients were more likely to use face masks “very often” (83% vs. 66% rural; P < .001), while hand sanitizer was used “very often” among 66% of urban and 57% of rural participants (P = .05).

Urban participants were more likely than were their rural counterparts to think themselves “somewhat” or “very” likely to develop COVID-19 (22% vs. 14%; P = .04).

It might be short-sighted for oncology and public health specialists to be dismissive of differences in infection mitigation behaviors and perceptions of vulnerability to SARS-CoV-2 infection. Those behaviors and perceptions of risk could lead to lower vaccination rates in rural areas. If that occurs, there would be major negative consequences for the long-term health of rural communities and their medically vulnerable residents.
 

Future directions

Although the first 6 months of the COVID-19 pandemic had disparate effects on cancer patients living in rural and urban counties, the reasons for the disparities are complex and not easily explained by this study.

It is possible that sequential administration of the survey during the pandemic would have uncovered greater variances in attitude and health-related behaviors.

As Ms. Daniels noted, when the survey was performed, Utah had not experienced a high frequency of COVID-19 cases. Furthermore, different levels of restrictions were implemented on a county-by-county basis, potentially influencing patients’ behaviors, psychosocial adjustment, and perceptions of risk.

In addition, there may have been differences in unmeasured endpoints (infection rates, medical care utilization via telemedicine, hospitalization rates, late effects, and mortality) between the urban and rural populations.

As the investigators concluded, further research is needed to better characterize the pandemic’s short- and long-term effects on cancer patients in rural and urban settings and appropriate interventions. Such studies may yield insights into the various facets of the well-documented “rural health gap” in cancer outcomes and interventions that could narrow the gap in spheres beyond the COVID-19 pandemic.

Ms. Daniels reported having no relevant disclosures.
 

Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers, as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.

Research has shown that, compared with their urban counterparts, rural cancer patients have higher cancer-related mortality and other negative treatment outcomes.

Among other explanations, the disparity has been attributed to lower education and income levels, medical and behavioral risk factors, differences in health literacy, and lower confidence in the medical system among rural residents (JCO Oncol Pract. 2020 Jul;16(7):422-30).

The COVID-19 and Oncology Patient Experience Consortium

Ms. Daniels explained that the COVID-19 and Oncology Patient Experience (COPES) Consortium was created to investigate various aspects of the patient experience during the pandemic. Three cancer centers – Moffitt Cancer Center, Huntsman Cancer Institute, and the Sylvester Comprehensive Cancer Center – participate in COPES.

At Huntsman, investigators studied social and health behaviors of cancer patients to assess whether there was a difference between those from rural and urban areas. The researchers looked at the impact of the pandemic on psychosocial outcomes, preventive measures patients implemented, and their perceptions of the risk of SARS-CoV-2 infection.

The team’s hypothesis was that rural patients might be more vulnerable than urban patients to the effects of social isolation, emotional distress, and health-adverse behaviors, but the investigators noted that there has been no prior research on the topic.
 

Assessing behaviors, attitudes, and outcomes

Between August and September 2020, the researchers surveyed 1,328 adult cancer patients who had visited Huntsman in the previous 4 years and who were enrolled in Huntsman’s Total Cancer Care or Precision Exercise Prescription studies.

Patients completed questionnaires that encompassed demographic and clinical factors, employment status, health behaviors, and infection preventive measures. Questionnaires were provided in electronic, paper, or phone-based formats. Information regarding age, race, ethnicity, and tumor stage was abstracted from Huntsman’s electronic health record.

Modifications in daily life and social interaction were assessed on a 5-point scale. Changes in exercise habits and alcohol consumption were assessed on a 3-point scale. Infection mitigation measures (the use of face masks and hand sanitizer) and perceptions about the likelihood of SARS-CoV-2 infection were measured.

The rural-urban community area codes system, which classifies U.S. census tracts by measures of population density, urbanization, and daily commuting, was utilized to categorize patients into rural and urban residences.
 

Characteristics of urban and rural cancer patients

There were 997 urban and 331 rural participants. The mean age was 60.1 years in the urban population and 62.6 years in the rural population (P = .01). There were no urban-rural differences in sex, ethnicity, cancer stage, or body mass index.

More urban than rural participants were employed full- or part-time (45% vs. 37%; P = .045). The rural counties had more patients who were not currently employed, primarily due to retirement (77% vs. 69% urban; P < .001).

“No health insurance coverage” was reported by 2% of urban and 4% of rural participants (P = .009), and 85% of all patients reported “good” to “excellent” overall health. Cancer patients in rural counties were significantly more likely to have ever smoked (37% vs. 25% urban; P = .001). In addition, alcohol consumption in the previous year was higher in rural patients. “Every day to less than once monthly” alcohol usage was reported by 44% of urban and 60% of rural patients (P < .001).
 

Changes in daily life and health-related behavior during the pandemic

Urban patients were more likely to report changes in their daily lives due to the pandemic. Specifically, 35% of urban patients and 26% of rural patients said the pandemic had changed their daily life “a lot” (P = .001).

However, there were no major differences between urban and rural patients when it came to changes in social interaction in the past month or feeling lonely in the past month (P = .45 and P = .88, respectively). Similarly, there were no significant differences for changes in alcohol consumption between the groups (P = .90).

Changes in exercise habits due to the pandemic were more common among patients in urban counties (51% vs. 39% rural; P < .001), though similar percentages of patients reported exercising less (44% urban vs. 45% rural) or more frequently (24% urban vs. 20% rural).

In terms of infection mitigation measures, urban patients were more likely to use face masks “very often” (83% vs. 66% rural; P < .001), while hand sanitizer was used “very often” among 66% of urban and 57% of rural participants (P = .05).

Urban participants were more likely than were their rural counterparts to think themselves “somewhat” or “very” likely to develop COVID-19 (22% vs. 14%; P = .04).

It might be short-sighted for oncology and public health specialists to be dismissive of differences in infection mitigation behaviors and perceptions of vulnerability to SARS-CoV-2 infection. Those behaviors and perceptions of risk could lead to lower vaccination rates in rural areas. If that occurs, there would be major negative consequences for the long-term health of rural communities and their medically vulnerable residents.
 

Future directions

Although the first 6 months of the COVID-19 pandemic had disparate effects on cancer patients living in rural and urban counties, the reasons for the disparities are complex and not easily explained by this study.

It is possible that sequential administration of the survey during the pandemic would have uncovered greater variances in attitude and health-related behaviors.

As Ms. Daniels noted, when the survey was performed, Utah had not experienced a high frequency of COVID-19 cases. Furthermore, different levels of restrictions were implemented on a county-by-county basis, potentially influencing patients’ behaviors, psychosocial adjustment, and perceptions of risk.

In addition, there may have been differences in unmeasured endpoints (infection rates, medical care utilization via telemedicine, hospitalization rates, late effects, and mortality) between the urban and rural populations.

As the investigators concluded, further research is needed to better characterize the pandemic’s short- and long-term effects on cancer patients in rural and urban settings and appropriate interventions. Such studies may yield insights into the various facets of the well-documented “rural health gap” in cancer outcomes and interventions that could narrow the gap in spheres beyond the COVID-19 pandemic.

Ms. Daniels reported having no relevant disclosures.
 

Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers, as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.

A new analysis of 11 phase 3/4 cardiovascular clinical trials conducted by the Thrombolysis in Myocardial Infarction (TIMI) group shows that women are more likely than men to discontinue study medications, and to withdraw from trials. The differences could not be explained by different frequencies of reporting adverse events, or by baseline differences.

©BananaStock/thinkstockphotos.com

The findings are significant, since cardiovascular drugs are routinely prescribed to women based on clinical trials that are populated largely by men, according to lead study author Emily Lau, MD, who is an advanced cardiology fellow at Massachusetts General Hospital, Boston. “It highlights an important disparity in clinical research in cardiology, because if women are already not represented well in clinical trials, and if once in clinical trials they don’t complete the study, it’s very hard to extrapolate the clinical trial findings to our female population in an accurate way,” Dr. Lau said in an interview. She also noted that sex-specific and reproductive factors are increasingly recognized as being important in the development and progression of cardiovascular disease.

A new analysis of 11 phase 3/4 cardiovascular clinical trials conducted by the Thrombolysis in Myocardial Infarction (TIMI) group shows that women are more likely than men to discontinue study medications, and to withdraw from trials. The differences could not be explained by different frequencies of reporting adverse events, or by baseline differences.

©BananaStock/thinkstockphotos.com

The findings are significant, since cardiovascular drugs are routinely prescribed to women based on clinical trials that are populated largely by men, according to lead study author Emily Lau, MD, who is an advanced cardiology fellow at Massachusetts General Hospital, Boston. “It highlights an important disparity in clinical research in cardiology, because if women are already not represented well in clinical trials, and if once in clinical trials they don’t complete the study, it’s very hard to extrapolate the clinical trial findings to our female population in an accurate way,” Dr. Lau said in an interview. She also noted that sex-specific and reproductive factors are increasingly recognized as being important in the development and progression of cardiovascular disease.

A new analysis of 11 phase 3/4 cardiovascular clinical trials conducted by the Thrombolysis in Myocardial Infarction (TIMI) group shows that women are more likely than men to discontinue study medications, and to withdraw from trials. The differences could not be explained by different frequencies of reporting adverse events, or by baseline differences.

©BananaStock/thinkstockphotos.com

The findings are significant, since cardiovascular drugs are routinely prescribed to women based on clinical trials that are populated largely by men, according to lead study author Emily Lau, MD, who is an advanced cardiology fellow at Massachusetts General Hospital, Boston. “It highlights an important disparity in clinical research in cardiology, because if women are already not represented well in clinical trials, and if once in clinical trials they don’t complete the study, it’s very hard to extrapolate the clinical trial findings to our female population in an accurate way,” Dr. Lau said in an interview. She also noted that sex-specific and reproductive factors are increasingly recognized as being important in the development and progression of cardiovascular disease.

After a long day in hematology clinic, I skimmed the inpatient list to see if any of my patients had been admitted. Seeing Ms. Short’s name (changed for privacy), a delightful African American woman I met during my early days of fellowship, had me making the trek to the hospital. She was living with multiple myeloma complicated by extramedullary manifestations that had significantly impacted her quality of life.

During our first encounter, she showed me a growing left subscapular mass the size of an orange that was erythematous, hot, painful, and irritated. As an enthusiastic first-year fellow, I wanted to be aggressive in addressing her concerns in response to her obvious distress about this mass. Ultimately, she left clinic with antibiotics and an appointment with radiation oncology to see if they could use radiation to shrink the subscapular mass.

When I went back in to discuss the plan with her, she grabbed my hand, looked me in my eyes and said: “Thank you, I’ve been mentioning this for a while and you’re the first person to get something done about it.” In that moment I knew that she felt seen.

By the time I made it over to the hospital, she was getting settled in her room to start another cycle of cytoreductive chemotherapy.

“I told them I had a Black doctor!” she exclaimed as I walked into her hospital room. “I was looking for you today in clinic ... I kept telling them I had a Black doctor, but the nurses kept telling me no, that there were only Black nurse practitioners.” She had repeatedly told the staff that I, her “Black doctor,” did indeed exist, and she went on to describe me as “you know, the [heavy-chested] and short Black doctor I saw early this fall.” To this day, her description still makes me chuckle.

Though I laughed at her description, it hurt that I had worked in a clinic for 6 months yet was invisible. Initially disappointed, I left Ms. Short’s room with a smile on my face, energized and encouraged.

My time with Ms. Short prompted me to ruminate on my experience as a Black physician. To put it in perspective, 5% of all physicians are Black, 2% are Black women, and 2.3% are oncologists, even though African Americans make up 13% of the general U.S. population. I reside in a space where I am simultaneously scrutinized because I am one of the few (or the only) Black physicians in the building, and yet I am invisible because my colleagues and coworkers routinely ignore my presence.

Black physicians, let alone hematologists, are so rare that nurses often cannot fathom that a Black woman could be more than a nurse practitioner. Sadly, this is the tip of the iceberg of some of the negative experiences I, and other Black doctors, have had.

How I present myself must be carefully curated to make progress in my career. My peers and superiors seem to hear me better when my hair is straight and not in its naturally curly state. My introversion has been interpreted as being standoffish or disinterested. Any tone other than happy is interpreted as “aggressive” or “angry”. Talking “too much” to Black support staff was reported to my program, as it was viewed as suspicious, disruptive, and “appearances matter”.

I am also expected to be nurturing in ways that White physicians are not required to be. In my presence, White physicians have denigrated an entire patient population that is disproportionately Black by calling them “sicklers.” If there is an interpersonal conflict, I must think about the long-term consequences of voicing my perspective. My non-Black colleagues do not have to think about these things.

Imagine dealing with this at work, then on your commute home being worried about the reality that you may be pulled over and become the next name on the ever-growing list of Black women and men murdered at the hands of police. The cognitive and emotional impact of being invisible is immense and cumulative over the years.

My Blackness creates a bias of inferiority that cannot be overcome by respectability, compliance, professionalism, training, and expertise. This is glaringly apparent on both sides of the physician-patient relationship. Black patients’ concerns are routinely overlooked and dismissed, as seen with Ms. Short, and are reflected in the Black maternal death rate, pain control in Black versus White patients, and personal experience as a patient and an advocate for my family members.

Patients have looked me in the face and said, “all lives matter,” displaying their refusal to recognize that systematic racism and inequality exist. These facts and experiences are the antithesis of “primum non nocere.”

Sadly, my and Ms. Short’s experiences are not singular ones, and racial bias in medicine is a diagnosed, but untreated cancer. Like the malignancies I treat, ignoring the problem has not made it go away; therefore, it continues to fester and spread, causing more destruction. It is of great importance and concern that all physicians recognize, reflect, and correct their implicit biases not only toward their patients, but also colleagues and trainees.

It seems that health care professionals can talk the talk, as many statements have been made against racism and implicit bias in medicine, but can we take true and meaningful action to begin the journey to equity and justice?

I would like to thank Adrienne Glover, MD, MaKenzie Hodge, MD, Maranatha McLean, MD, and Darion Showell, MD, for our stimulating conversations that helped me put pen to paper. I’d also like to thank my family for being my editors.

Daphanie D. Taylor, MD, is a hematology/oncology fellow PGY-6 at Levine Cancer Institute, Charlotte, N.C.

References and further reading

Roy L. “‘It’s My Calling To Change The Statistics’: Why We Need More Black Female Physicians.” Forbes Magazine, 27 Feb. 2020.

“Diversity in Medicine: Facts and Figures 2019.” Association of American Medical Colleges, 2019.

“Facts & Figures: Diversity in Oncology.” American Society of Clinical Oncology. 2020 Jan 16.

After a long day in hematology clinic, I skimmed the inpatient list to see if any of my patients had been admitted. Seeing Ms. Short’s name (changed for privacy), a delightful African American woman I met during my early days of fellowship, had me making the trek to the hospital. She was living with multiple myeloma complicated by extramedullary manifestations that had significantly impacted her quality of life.

During our first encounter, she showed me a growing left subscapular mass the size of an orange that was erythematous, hot, painful, and irritated. As an enthusiastic first-year fellow, I wanted to be aggressive in addressing her concerns in response to her obvious distress about this mass. Ultimately, she left clinic with antibiotics and an appointment with radiation oncology to see if they could use radiation to shrink the subscapular mass.

When I went back in to discuss the plan with her, she grabbed my hand, looked me in my eyes and said: “Thank you, I’ve been mentioning this for a while and you’re the first person to get something done about it.” In that moment I knew that she felt seen.

By the time I made it over to the hospital, she was getting settled in her room to start another cycle of cytoreductive chemotherapy.

“I told them I had a Black doctor!” she exclaimed as I walked into her hospital room. “I was looking for you today in clinic ... I kept telling them I had a Black doctor, but the nurses kept telling me no, that there were only Black nurse practitioners.” She had repeatedly told the staff that I, her “Black doctor,” did indeed exist, and she went on to describe me as “you know, the [heavy-chested] and short Black doctor I saw early this fall.” To this day, her description still makes me chuckle.

Though I laughed at her description, it hurt that I had worked in a clinic for 6 months yet was invisible. Initially disappointed, I left Ms. Short’s room with a smile on my face, energized and encouraged.

My time with Ms. Short prompted me to ruminate on my experience as a Black physician. To put it in perspective, 5% of all physicians are Black, 2% are Black women, and 2.3% are oncologists, even though African Americans make up 13% of the general U.S. population. I reside in a space where I am simultaneously scrutinized because I am one of the few (or the only) Black physicians in the building, and yet I am invisible because my colleagues and coworkers routinely ignore my presence.

Black physicians, let alone hematologists, are so rare that nurses often cannot fathom that a Black woman could be more than a nurse practitioner. Sadly, this is the tip of the iceberg of some of the negative experiences I, and other Black doctors, have had.

How I present myself must be carefully curated to make progress in my career. My peers and superiors seem to hear me better when my hair is straight and not in its naturally curly state. My introversion has been interpreted as being standoffish or disinterested. Any tone other than happy is interpreted as “aggressive” or “angry”. Talking “too much” to Black support staff was reported to my program, as it was viewed as suspicious, disruptive, and “appearances matter”.

I am also expected to be nurturing in ways that White physicians are not required to be. In my presence, White physicians have denigrated an entire patient population that is disproportionately Black by calling them “sicklers.” If there is an interpersonal conflict, I must think about the long-term consequences of voicing my perspective. My non-Black colleagues do not have to think about these things.

Imagine dealing with this at work, then on your commute home being worried about the reality that you may be pulled over and become the next name on the ever-growing list of Black women and men murdered at the hands of police. The cognitive and emotional impact of being invisible is immense and cumulative over the years.

My Blackness creates a bias of inferiority that cannot be overcome by respectability, compliance, professionalism, training, and expertise. This is glaringly apparent on both sides of the physician-patient relationship. Black patients’ concerns are routinely overlooked and dismissed, as seen with Ms. Short, and are reflected in the Black maternal death rate, pain control in Black versus White patients, and personal experience as a patient and an advocate for my family members.

Patients have looked me in the face and said, “all lives matter,” displaying their refusal to recognize that systematic racism and inequality exist. These facts and experiences are the antithesis of “primum non nocere.”

Sadly, my and Ms. Short’s experiences are not singular ones, and racial bias in medicine is a diagnosed, but untreated cancer. Like the malignancies I treat, ignoring the problem has not made it go away; therefore, it continues to fester and spread, causing more destruction. It is of great importance and concern that all physicians recognize, reflect, and correct their implicit biases not only toward their patients, but also colleagues and trainees.

It seems that health care professionals can talk the talk, as many statements have been made against racism and implicit bias in medicine, but can we take true and meaningful action to begin the journey to equity and justice?

I would like to thank Adrienne Glover, MD, MaKenzie Hodge, MD, Maranatha McLean, MD, and Darion Showell, MD, for our stimulating conversations that helped me put pen to paper. I’d also like to thank my family for being my editors.

Daphanie D. Taylor, MD, is a hematology/oncology fellow PGY-6 at Levine Cancer Institute, Charlotte, N.C.

References and further reading

Roy L. “‘It’s My Calling To Change The Statistics’: Why We Need More Black Female Physicians.” Forbes Magazine, 27 Feb. 2020.

“Diversity in Medicine: Facts and Figures 2019.” Association of American Medical Colleges, 2019.

“Facts & Figures: Diversity in Oncology.” American Society of Clinical Oncology. 2020 Jan 16.

After a long day in hematology clinic, I skimmed the inpatient list to see if any of my patients had been admitted. Seeing Ms. Short’s name (changed for privacy), a delightful African American woman I met during my early days of fellowship, had me making the trek to the hospital. She was living with multiple myeloma complicated by extramedullary manifestations that had significantly impacted her quality of life.

During our first encounter, she showed me a growing left subscapular mass the size of an orange that was erythematous, hot, painful, and irritated. As an enthusiastic first-year fellow, I wanted to be aggressive in addressing her concerns in response to her obvious distress about this mass. Ultimately, she left clinic with antibiotics and an appointment with radiation oncology to see if they could use radiation to shrink the subscapular mass.

When I went back in to discuss the plan with her, she grabbed my hand, looked me in my eyes and said: “Thank you, I’ve been mentioning this for a while and you’re the first person to get something done about it.” In that moment I knew that she felt seen.

By the time I made it over to the hospital, she was getting settled in her room to start another cycle of cytoreductive chemotherapy.

“I told them I had a Black doctor!” she exclaimed as I walked into her hospital room. “I was looking for you today in clinic ... I kept telling them I had a Black doctor, but the nurses kept telling me no, that there were only Black nurse practitioners.” She had repeatedly told the staff that I, her “Black doctor,” did indeed exist, and she went on to describe me as “you know, the [heavy-chested] and short Black doctor I saw early this fall.” To this day, her description still makes me chuckle.

Though I laughed at her description, it hurt that I had worked in a clinic for 6 months yet was invisible. Initially disappointed, I left Ms. Short’s room with a smile on my face, energized and encouraged.

My time with Ms. Short prompted me to ruminate on my experience as a Black physician. To put it in perspective, 5% of all physicians are Black, 2% are Black women, and 2.3% are oncologists, even though African Americans make up 13% of the general U.S. population. I reside in a space where I am simultaneously scrutinized because I am one of the few (or the only) Black physicians in the building, and yet I am invisible because my colleagues and coworkers routinely ignore my presence.

Black physicians, let alone hematologists, are so rare that nurses often cannot fathom that a Black woman could be more than a nurse practitioner. Sadly, this is the tip of the iceberg of some of the negative experiences I, and other Black doctors, have had.

How I present myself must be carefully curated to make progress in my career. My peers and superiors seem to hear me better when my hair is straight and not in its naturally curly state. My introversion has been interpreted as being standoffish or disinterested. Any tone other than happy is interpreted as “aggressive” or “angry”. Talking “too much” to Black support staff was reported to my program, as it was viewed as suspicious, disruptive, and “appearances matter”.

I am also expected to be nurturing in ways that White physicians are not required to be. In my presence, White physicians have denigrated an entire patient population that is disproportionately Black by calling them “sicklers.” If there is an interpersonal conflict, I must think about the long-term consequences of voicing my perspective. My non-Black colleagues do not have to think about these things.

Imagine dealing with this at work, then on your commute home being worried about the reality that you may be pulled over and become the next name on the ever-growing list of Black women and men murdered at the hands of police. The cognitive and emotional impact of being invisible is immense and cumulative over the years.

My Blackness creates a bias of inferiority that cannot be overcome by respectability, compliance, professionalism, training, and expertise. This is glaringly apparent on both sides of the physician-patient relationship. Black patients’ concerns are routinely overlooked and dismissed, as seen with Ms. Short, and are reflected in the Black maternal death rate, pain control in Black versus White patients, and personal experience as a patient and an advocate for my family members.

Patients have looked me in the face and said, “all lives matter,” displaying their refusal to recognize that systematic racism and inequality exist. These facts and experiences are the antithesis of “primum non nocere.”

Sadly, my and Ms. Short’s experiences are not singular ones, and racial bias in medicine is a diagnosed, but untreated cancer. Like the malignancies I treat, ignoring the problem has not made it go away; therefore, it continues to fester and spread, causing more destruction. It is of great importance and concern that all physicians recognize, reflect, and correct their implicit biases not only toward their patients, but also colleagues and trainees.

It seems that health care professionals can talk the talk, as many statements have been made against racism and implicit bias in medicine, but can we take true and meaningful action to begin the journey to equity and justice?

I would like to thank Adrienne Glover, MD, MaKenzie Hodge, MD, Maranatha McLean, MD, and Darion Showell, MD, for our stimulating conversations that helped me put pen to paper. I’d also like to thank my family for being my editors.

Daphanie D. Taylor, MD, is a hematology/oncology fellow PGY-6 at Levine Cancer Institute, Charlotte, N.C.

References and further reading

Roy L. “‘It’s My Calling To Change The Statistics’: Why We Need More Black Female Physicians.” Forbes Magazine, 27 Feb. 2020.

“Diversity in Medicine: Facts and Figures 2019.” Association of American Medical Colleges, 2019.

“Facts & Figures: Diversity in Oncology.” American Society of Clinical Oncology. 2020 Jan 16.

Warning: This article will be about Tom Brady. If you love Tom Brady, hate Tom Brady, previously loved and now hate Tom Brady, I’m just warning you so you’ll be in the right frame of mind to continue. (If you don’t know who Tom Brady is, he’s Gisele’s husband).

Some of the best doctors I’ve ever seen in action were emeritus physicians. In medical school at Wake Forest University, one of my professors was Dr. Eben Alexander. A retired neurosurgeon, he taught a case-based critical thinking skills class. I recall his brilliant insight and coaching, working through cases that had nothing to do with the brain or with surgery. He used his vast experience and wisdom to teach us how to practice medicine. He was, at that time, nearly 90 years old. Despite having been retired for decades, he was still writing articles and editing journals. He was inspiring. For a minute, he had me thinking I’d like to be a neurosurgeon, so I could be just like Eben Alexander. I did not, but I learned things from him that still impact my practice as a dermatologist today.

I’m sure you’ve had similar experiences of older colleagues or mentors who were the best doctor in the clinic or the O.R. They are the Dr. Anthony Faucis, not just practicing, but leading while in their 8th or 9th decade. We are all so fortunate that they keep playing.

We’ve not made our final choices on whom to hire, but with two positions, I expect we’ll choose both a young doctor and an experienced one to add to our team. It will be fun to watch and learn from them. Just like it will be fun to watch Tom Brady in the Super Bowl again next year.

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at [email protected].

Warning: This article will be about Tom Brady. If you love Tom Brady, hate Tom Brady, previously loved and now hate Tom Brady, I’m just warning you so you’ll be in the right frame of mind to continue. (If you don’t know who Tom Brady is, he’s Gisele’s husband).

Some of the best doctors I’ve ever seen in action were emeritus physicians. In medical school at Wake Forest University, one of my professors was Dr. Eben Alexander. A retired neurosurgeon, he taught a case-based critical thinking skills class. I recall his brilliant insight and coaching, working through cases that had nothing to do with the brain or with surgery. He used his vast experience and wisdom to teach us how to practice medicine. He was, at that time, nearly 90 years old. Despite having been retired for decades, he was still writing articles and editing journals. He was inspiring. For a minute, he had me thinking I’d like to be a neurosurgeon, so I could be just like Eben Alexander. I did not, but I learned things from him that still impact my practice as a dermatologist today.

I’m sure you’ve had similar experiences of older colleagues or mentors who were the best doctor in the clinic or the O.R. They are the Dr. Anthony Faucis, not just practicing, but leading while in their 8th or 9th decade. We are all so fortunate that they keep playing.

We’ve not made our final choices on whom to hire, but with two positions, I expect we’ll choose both a young doctor and an experienced one to add to our team. It will be fun to watch and learn from them. Just like it will be fun to watch Tom Brady in the Super Bowl again next year.

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at [email protected].

Warning: This article will be about Tom Brady. If you love Tom Brady, hate Tom Brady, previously loved and now hate Tom Brady, I’m just warning you so you’ll be in the right frame of mind to continue. (If you don’t know who Tom Brady is, he’s Gisele’s husband).

Some of the best doctors I’ve ever seen in action were emeritus physicians. In medical school at Wake Forest University, one of my professors was Dr. Eben Alexander. A retired neurosurgeon, he taught a case-based critical thinking skills class. I recall his brilliant insight and coaching, working through cases that had nothing to do with the brain or with surgery. He used his vast experience and wisdom to teach us how to practice medicine. He was, at that time, nearly 90 years old. Despite having been retired for decades, he was still writing articles and editing journals. He was inspiring. For a minute, he had me thinking I’d like to be a neurosurgeon, so I could be just like Eben Alexander. I did not, but I learned things from him that still impact my practice as a dermatologist today.

I’m sure you’ve had similar experiences of older colleagues or mentors who were the best doctor in the clinic or the O.R. They are the Dr. Anthony Faucis, not just practicing, but leading while in their 8th or 9th decade. We are all so fortunate that they keep playing.

We’ve not made our final choices on whom to hire, but with two positions, I expect we’ll choose both a young doctor and an experienced one to add to our team. It will be fun to watch and learn from them. Just like it will be fun to watch Tom Brady in the Super Bowl again next year.

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at [email protected].

A large hyperpigmented patch with overlying darker macules and papules is characteristic of a speckled lentiginous nevus (SLN), also called a nevus spilus.

SLN is a cafe-au-lait˗like nevus that initially appears with a hyperpigmented background, usually at or around birth. Later, a speckled or polka-dot pattern of dark macules and papules appears over time. SLN is believed to be a form of congenital melanocytic nevus. There are believed to be 2 subtypes of SLN: nevus spilus maculosus and nevus spilus papulosus.

The maculosus subtype is characterized by flat and evenly distributed macules, that look like polka-dots. Histopathology reveals elongated interpapillary ridges containing increased numbers of melanocytes that form nests at the dermo-epidermal junction.

The papulosus subtype (which this patient had) is differentiated by superimposed speckles and papules whose size and distribution vary; this subype looks similar to a starry sky. Histopathology of the papulosus subtype shows melanocytic nevi of either the dermal or compound type—hence the papular appearance.

Given that SLN is a congenital melanocytic nevus, there is a small risk of transformation to malignant melanoma. The papulosus subtype is believed to have a more dynamic course with more lesions appearing over time. The maculosus subtype is considered to have a slightly higher risk of transformation into malignant melanoma compared to the papulosus subtype.

It is important to recognize that SLN is a distinct clinical entity, rather than a large irregular nevus. Mistaking it for a large suspicious nevus would require multiple biopsies of the most suspicious areas or excision of the entire lesion. Treatment for SLN includes serial surveillance with biopsy or excision of any suspicious areas that arise. In this case, the patient did not have any areas warranting biopsy, so the plan was to have him followed with annual clinical surveillance.

‌

Photo and text courtesy of Erik Unruh, MD, MPH, and Daniel Stulberg, MD, FAAFP, Department of Family and Community Medicine, University of New Mexico School of Medicine, Albuquerque.

A large hyperpigmented patch with overlying darker macules and papules is characteristic of a speckled lentiginous nevus (SLN), also called a nevus spilus.

SLN is a cafe-au-lait˗like nevus that initially appears with a hyperpigmented background, usually at or around birth. Later, a speckled or polka-dot pattern of dark macules and papules appears over time. SLN is believed to be a form of congenital melanocytic nevus. There are believed to be 2 subtypes of SLN: nevus spilus maculosus and nevus spilus papulosus.

The maculosus subtype is characterized by flat and evenly distributed macules, that look like polka-dots. Histopathology reveals elongated interpapillary ridges containing increased numbers of melanocytes that form nests at the dermo-epidermal junction.

The papulosus subtype (which this patient had) is differentiated by superimposed speckles and papules whose size and distribution vary; this subype looks similar to a starry sky. Histopathology of the papulosus subtype shows melanocytic nevi of either the dermal or compound type—hence the papular appearance.

Given that SLN is a congenital melanocytic nevus, there is a small risk of transformation to malignant melanoma. The papulosus subtype is believed to have a more dynamic course with more lesions appearing over time. The maculosus subtype is considered to have a slightly higher risk of transformation into malignant melanoma compared to the papulosus subtype.

It is important to recognize that SLN is a distinct clinical entity, rather than a large irregular nevus. Mistaking it for a large suspicious nevus would require multiple biopsies of the most suspicious areas or excision of the entire lesion. Treatment for SLN includes serial surveillance with biopsy or excision of any suspicious areas that arise. In this case, the patient did not have any areas warranting biopsy, so the plan was to have him followed with annual clinical surveillance.

‌

Photo and text courtesy of Erik Unruh, MD, MPH, and Daniel Stulberg, MD, FAAFP, Department of Family and Community Medicine, University of New Mexico School of Medicine, Albuquerque.

A large hyperpigmented patch with overlying darker macules and papules is characteristic of a speckled lentiginous nevus (SLN), also called a nevus spilus.

SLN is a cafe-au-lait˗like nevus that initially appears with a hyperpigmented background, usually at or around birth. Later, a speckled or polka-dot pattern of dark macules and papules appears over time. SLN is believed to be a form of congenital melanocytic nevus. There are believed to be 2 subtypes of SLN: nevus spilus maculosus and nevus spilus papulosus.

The maculosus subtype is characterized by flat and evenly distributed macules, that look like polka-dots. Histopathology reveals elongated interpapillary ridges containing increased numbers of melanocytes that form nests at the dermo-epidermal junction.

The papulosus subtype (which this patient had) is differentiated by superimposed speckles and papules whose size and distribution vary; this subype looks similar to a starry sky. Histopathology of the papulosus subtype shows melanocytic nevi of either the dermal or compound type—hence the papular appearance.

Given that SLN is a congenital melanocytic nevus, there is a small risk of transformation to malignant melanoma. The papulosus subtype is believed to have a more dynamic course with more lesions appearing over time. The maculosus subtype is considered to have a slightly higher risk of transformation into malignant melanoma compared to the papulosus subtype.

It is important to recognize that SLN is a distinct clinical entity, rather than a large irregular nevus. Mistaking it for a large suspicious nevus would require multiple biopsies of the most suspicious areas or excision of the entire lesion. Treatment for SLN includes serial surveillance with biopsy or excision of any suspicious areas that arise. In this case, the patient did not have any areas warranting biopsy, so the plan was to have him followed with annual clinical surveillance.

‌

Photo and text courtesy of Erik Unruh, MD, MPH, and Daniel Stulberg, MD, FAAFP, Department of Family and Community Medicine, University of New Mexico School of Medicine, Albuquerque.

There are two pandemics permeating the United States: COVID-19 and addiction. To date, more than 468,000 people have died from COVID-19 in the U.S. In the 12-month period ending in May 2020, over 80,000 died from a drug related cause – the highest number ever recorded in a year. Many of these deaths involved opioids.

COVID-19 has worsened outcomes for people with addiction. There is less access to treatment, increased isolation, and worsening psychosocial and economic stressors. These factors may drive new, increased, or more risky substance use and return to use for people in recovery. As hospitalists, we have been responders in both COVID-19 and our country’s worsening overdose and addiction crisis.

In December 2020’s Journal of Hospital Medicine article “Converging Crises: Caring for hospitalized adults with substance use disorder in the time of COVID-19”, Dr. Honora Englander and her coauthors called on hospitalists to actively engage patients with substance use disorders during hospitalization. The article highlights the colliding crises of addiction and COVID-19 and provides eight practical approaches for hospitalists to address substance use disorders during the pandemic, including initiating buprenorphine for opioid withdrawal and prescribing it for opioid use disorder (OUD) treatment.

Buprenorphine effectively treats opioid withdrawal, reduces OUD-related mortality, and decreases hospital readmissions related to OUD. To prescribe buprenorphine for OUD in the outpatient setting or on hospital discharge, providers need an X-Waiver. The X-Waiver is a result of the Drug Addiction Treatment Act 2000 (DATA 2000), which was enacted in 2000. It permits physicians to prescribe buprenorphine for OUD treatment after an 8-hour training. In 2016, the Comprehensive Addiction and Recovery Act extended buprenorphine prescribing to physician assistants (PAs) and advanced-practice nurses (APNs). However, PAs and APNs are required to complete a 24-hour training to receive the waiver.

There is a large body of evidence regarding buprenorphine’s safety and efficacy in OUD treatment. With a worsening overdose crisis, there have been increasing opioid-related hospitalizations. When new medications for diabetes, hypertension, or DVT treatment become available, as hospitalists we incorporate them into our toolbox. As buprenorphine becomes more accessible, we can be leaders in further adopting it (and other substance use disorder medications while we are at it) as our standard of care for people with OUD.

Dr. Bottner is a physician assistant in the Division of Hospital Medicine at Dell Medical School at The University of Texas at Austin and director of the hospital’s Buprenorphine Team. Dr. Martin is a board-certified addiction medicine physician and hospitalist at University of California, San Francisco, and director of the Addiction Care Team at San Francisco General Hospital. Dr. Bottner and Dr. Martin colead the SHM Substance Use Disorder Special Interest Group.

There are two pandemics permeating the United States: COVID-19 and addiction. To date, more than 468,000 people have died from COVID-19 in the U.S. In the 12-month period ending in May 2020, over 80,000 died from a drug related cause – the highest number ever recorded in a year. Many of these deaths involved opioids.

COVID-19 has worsened outcomes for people with addiction. There is less access to treatment, increased isolation, and worsening psychosocial and economic stressors. These factors may drive new, increased, or more risky substance use and return to use for people in recovery. As hospitalists, we have been responders in both COVID-19 and our country’s worsening overdose and addiction crisis.

In December 2020’s Journal of Hospital Medicine article “Converging Crises: Caring for hospitalized adults with substance use disorder in the time of COVID-19”, Dr. Honora Englander and her coauthors called on hospitalists to actively engage patients with substance use disorders during hospitalization. The article highlights the colliding crises of addiction and COVID-19 and provides eight practical approaches for hospitalists to address substance use disorders during the pandemic, including initiating buprenorphine for opioid withdrawal and prescribing it for opioid use disorder (OUD) treatment.

Buprenorphine effectively treats opioid withdrawal, reduces OUD-related mortality, and decreases hospital readmissions related to OUD. To prescribe buprenorphine for OUD in the outpatient setting or on hospital discharge, providers need an X-Waiver. The X-Waiver is a result of the Drug Addiction Treatment Act 2000 (DATA 2000), which was enacted in 2000. It permits physicians to prescribe buprenorphine for OUD treatment after an 8-hour training. In 2016, the Comprehensive Addiction and Recovery Act extended buprenorphine prescribing to physician assistants (PAs) and advanced-practice nurses (APNs). However, PAs and APNs are required to complete a 24-hour training to receive the waiver.

There is a large body of evidence regarding buprenorphine’s safety and efficacy in OUD treatment. With a worsening overdose crisis, there have been increasing opioid-related hospitalizations. When new medications for diabetes, hypertension, or DVT treatment become available, as hospitalists we incorporate them into our toolbox. As buprenorphine becomes more accessible, we can be leaders in further adopting it (and other substance use disorder medications while we are at it) as our standard of care for people with OUD.

Dr. Bottner is a physician assistant in the Division of Hospital Medicine at Dell Medical School at The University of Texas at Austin and director of the hospital’s Buprenorphine Team. Dr. Martin is a board-certified addiction medicine physician and hospitalist at University of California, San Francisco, and director of the Addiction Care Team at San Francisco General Hospital. Dr. Bottner and Dr. Martin colead the SHM Substance Use Disorder Special Interest Group.

There are two pandemics permeating the United States: COVID-19 and addiction. To date, more than 468,000 people have died from COVID-19 in the U.S. In the 12-month period ending in May 2020, over 80,000 died from a drug related cause – the highest number ever recorded in a year. Many of these deaths involved opioids.

COVID-19 has worsened outcomes for people with addiction. There is less access to treatment, increased isolation, and worsening psychosocial and economic stressors. These factors may drive new, increased, or more risky substance use and return to use for people in recovery. As hospitalists, we have been responders in both COVID-19 and our country’s worsening overdose and addiction crisis.

In December 2020’s Journal of Hospital Medicine article “Converging Crises: Caring for hospitalized adults with substance use disorder in the time of COVID-19”, Dr. Honora Englander and her coauthors called on hospitalists to actively engage patients with substance use disorders during hospitalization. The article highlights the colliding crises of addiction and COVID-19 and provides eight practical approaches for hospitalists to address substance use disorders during the pandemic, including initiating buprenorphine for opioid withdrawal and prescribing it for opioid use disorder (OUD) treatment.

Buprenorphine effectively treats opioid withdrawal, reduces OUD-related mortality, and decreases hospital readmissions related to OUD. To prescribe buprenorphine for OUD in the outpatient setting or on hospital discharge, providers need an X-Waiver. The X-Waiver is a result of the Drug Addiction Treatment Act 2000 (DATA 2000), which was enacted in 2000. It permits physicians to prescribe buprenorphine for OUD treatment after an 8-hour training. In 2016, the Comprehensive Addiction and Recovery Act extended buprenorphine prescribing to physician assistants (PAs) and advanced-practice nurses (APNs). However, PAs and APNs are required to complete a 24-hour training to receive the waiver.

There is a large body of evidence regarding buprenorphine’s safety and efficacy in OUD treatment. With a worsening overdose crisis, there have been increasing opioid-related hospitalizations. When new medications for diabetes, hypertension, or DVT treatment become available, as hospitalists we incorporate them into our toolbox. As buprenorphine becomes more accessible, we can be leaders in further adopting it (and other substance use disorder medications while we are at it) as our standard of care for people with OUD.

Dr. Bottner is a physician assistant in the Division of Hospital Medicine at Dell Medical School at The University of Texas at Austin and director of the hospital’s Buprenorphine Team. Dr. Martin is a board-certified addiction medicine physician and hospitalist at University of California, San Francisco, and director of the Addiction Care Team at San Francisco General Hospital. Dr. Bottner and Dr. Martin colead the SHM Substance Use Disorder Special Interest Group.

Despite improvements in prevention of graft-versus-host disease, chronic GVHD still occurs in 10%-50% of patients who undergo an allogeneic hematopoietic stem cell transplant, and these patients may require prolonged treatment with multiple lines of therapy, said a hematologist and transplant researcher.

“More effective, less toxic therapies for chronic GVHD are needed,” Stephanie Lee, MD, MPH, from the Fred Hutchinson Cancer Research Center in Seattle said at the Transplant & Cellular Therapies Meetings.

Dr. Lee reviewed clinical trials for chronic GVHD at the meeting held by the American Society for Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research.

Although the incidence of chronic GVHD has gradually declined over the last 40 years and both relapse-free and overall survival following a chronic GVHD diagnosis have improved, “for patients who are diagnosed with chronic GVHD, they still will see many lines of therapy and many years of therapy,” she said.

Among 148 patients with chronic GVHD treated at her center, for example, 66% went on to two lines of therapy, 50% went on to three lines, 37% required four lines of therapy, and 20% needed five lines or more.

Salvage therapies for patients with chronic GVHD have evolved away from immunomodulators and immunosuppressants in the early 1990s, toward monoclonal antibodies such as rituximab in the early 2000s, to interleukin-2 and to tyrosine kinase inhibitors such as ruxolitinib (Jakafi) and ibrutinib (Imbruvica).

There are currently 36 agents that are FDA approved for at least one indication and can also be prescribed for the treatment of chronic GVHD, Dr. Lee noted.
 

Treatment goals

Dr. Lee laid out six goals for treating patients with chronic GVHD. They include:

• Controlling current signs and symptoms, measured by response rates and patient-reported outcomes
• Preventing further tissue and organ damage
• Minimizing toxicity
• Maintaining graft-versus-tumor effect
• Achieving graft tolerance and stopping immunosuppression
• Decreasing nonrelapse mortality and improving survival

Active trials

Dr. Lee identified 33 trials with chronic GVHD as an indication that are currently recruiting, and an additional 13 trials that are active but closed to recruiting. The trials can be generally grouped by mechanism of action, and involve agents targeting T-regulatory cells, B cells and/or B-cell receptor (BCR) signaling, monocytes/macrophages, costimulatory blockage, a proteasome inhibition, Janus kinase (JAK) 1/2 inhibitors, ROCK2 inhibitors, hedgehog pathway inhibition, cellular therapy, and organ-targeted therapy.

Most of the trials have overall response rate as the primary endpoint, and all but five are currently in phase 1 or 2. The currently active phase 3 trials include two with ibrutinib, one with the investigational agent itacitinib, one with ruxolitinib, and one with mesenchymal stem cells.

“I’ll note that, when results are reported, the denominator really matters for the overall response rate, especially if you’re talking about small trials, because if you require the patient to be treated with an agent for a certain period of time, and you take out all the people who didn’t make it to that time point, then your overall response rate looks better,” she said.
 

BTK inhibitors

The first-in-class Bruton tyrosine kinase (BTK) inhibitor ibrutinib was the first and thus far only agent approved by the Food and Drug Administration for chronic GVHD. The approval was based on a single-arm, multicenter trial with 42 patients.

The ORR in this trial was 69%, consisting of 31% complete responses and 38% partial responses, with a duration of response longer than 10 months in slightly more than half of all patients. In all, 24% of patients had improvement of symptoms in two consecutive visits, and 29% continued on ibrutinib at the time of the primary analysis in 2017.

Based on these promising results, acalabrutinib, which is more potent and selective for BTK than ibrutinib, with no effect on either platelets or natural killer cells, is currently under investigation in a phase 2 trial in 50 patients at a dose of 100 mg orally twice daily.
 

JAK1/2 inhibition

The JAK1 inhibitor itacitinib failed to meet its primary ORR endpoint in the phase 3 GRAVITAS-301 study, according to a press release, but the manufacturer (Incyte) said that it is continuing its commitment to JAK inhibitors with ruxolitinib, which has shown activity against acute, steroid-refractory GVHD, and is being explored for prevention of chronic GVHD in the randomized, phase 3 REACH3 study.

The trial met its primary endpoint for a higher ORR at week 24 with ruxolitinib versus best available therapy, at 49.7% versus 25.6%, respectively, which translated into an odds ratio for response with the JAK inhibitor of 2.99 (P < .0001).
 

Selective T-cell expansion

Efavaleukin alfa is an IL-2-mutated protein (mutein), with a mutation in the IL-2RB-binding portion of IL-2 causing increased selectivity for regulatory T-cell expansion. It is bound to an IgG-Fc domain that is itself mutated, with reduced Fc receptor binding and IgG effector function to give it a longer half life. This agent is being studied in a phase 1/2 trial in a subcutaneous formulation delivered every 1 or 2 weeks to 68 patients.

Monocyte/macrophage depletion

Axatilimab is a high-affinity antibody targeting colony stimulating factor–1 receptor (CSF-1R) expressed on monocytes and macrophages. By blocking CSF-1R, it depletes circulation of nonclassical monocytes and prevents the differentiation and survival of M2 macrophages in tissue.

It is currently being investigated 30 patients in a phase 1/2 study in an intravenous formulation delivered over 30 minutes every 2-4 weeks.
 

Hedgehog pathway inhibition

There is evidence suggesting that hedgehog pathway inhibition can lessen fibrosis. Glasdegib (Daurismo) a potent selective oral inhibitor of the hedgehog signaling pathway, is approved for use with low-dose cytarabine for patients with newly diagnosed acute myeloid leukemia aged older than 75 years or have comorbidities precluding intensive chemotherapy.

This agent is associated with drug intolerance because of muscle spasms, dysgeusia, and alopecia, however.

The drug is currently in phase 1/2 at a dose of 50 mg orally per day in 20 patients.
 

ROCK2 inhibition

Belumosudil (formerly KD025) “appears to rebalance the immune system,” Dr. Lee said. Investigators think that the drug dampens an autoaggressive inflammatory response by selective inhibition of ROCK2.

This drug has been studied in a dose-escalation study and a phase 2 trial, in which 132 participants were randomized to receive belumosudil 200 mg either once or twice daily.

At a median follow-up of 8 months, the ORR with belumosudil 200 mg once and twice daily was 73% and 74%, respectively. Similar results were seen in patients who had previously received either ruxolitinib or ibrutinib. High response rates were seen in patients with severe chronic GVHD, involvement of four or more organs and a refractory response to their last line of therapy.
 

Hard-to-manage patients

“We’re very hopeful for many of these agents, but we have to acknowledge that there are still many management dilemmas, patients that we just don’t really know what to do with,” Dr. Lee said. “These include patients who have bad sclerosis and fasciitis, nonhealing skin ulcers, bronchiolitis obliterans, serositis that can be very difficult to manage, severe keratoconjunctivitis that can be eyesight threatening, nonhealing mouth ulcers, esophageal structures, and always patients who have frequent infections.

“We are hopeful that some these agents will be useful for our patients who have severe manifestations, but often the number of patients with these manifestations in the trials is too low to say something specific about them,” she added.
 

‘Exciting time’

“It’s an exciting time because there are a lot of different drugs that are being studied for chronic GVHD,” commented Betty Hamilton, MD, a hematologist/oncologist at the Cleveland Clinic.

“I think that where the field is going in terms of treatment is recognizing that chronic GVHD is a pretty heterogeneous disease, and we have to learn even more about the underlying biologic pathways to be able to determine which class of drugs to use and when,” she said in an interview.

She agreed with Dr. Lee that the goals of treating patients with chronic GVHD include improving symptoms and quality, preventing progression, ideally tapering patients off immunosuppression, and achieving a balance between preventing negative consequences of GVHD while maintain the benefits of a graft-versus-leukemia effect.

“In our center, drug choice is based on physician preference and comfort with how often they’ve used the drug, patients’ comorbidities, toxicities of the drug, and logistical considerations,” Dr. Hamilton said.

Dr. Lee disclosed consulting activities for Pfizer and Kadmon, travel and lodging from Amgen, and research funding from those companies and others. Dr. Hamilton disclosed consulting for Syndax and Incyte.

Despite improvements in prevention of graft-versus-host disease, chronic GVHD still occurs in 10%-50% of patients who undergo an allogeneic hematopoietic stem cell transplant, and these patients may require prolonged treatment with multiple lines of therapy, said a hematologist and transplant researcher.

“More effective, less toxic therapies for chronic GVHD are needed,” Stephanie Lee, MD, MPH, from the Fred Hutchinson Cancer Research Center in Seattle said at the Transplant & Cellular Therapies Meetings.

Dr. Lee reviewed clinical trials for chronic GVHD at the meeting held by the American Society for Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research.

Although the incidence of chronic GVHD has gradually declined over the last 40 years and both relapse-free and overall survival following a chronic GVHD diagnosis have improved, “for patients who are diagnosed with chronic GVHD, they still will see many lines of therapy and many years of therapy,” she said.

Among 148 patients with chronic GVHD treated at her center, for example, 66% went on to two lines of therapy, 50% went on to three lines, 37% required four lines of therapy, and 20% needed five lines or more.

Salvage therapies for patients with chronic GVHD have evolved away from immunomodulators and immunosuppressants in the early 1990s, toward monoclonal antibodies such as rituximab in the early 2000s, to interleukin-2 and to tyrosine kinase inhibitors such as ruxolitinib (Jakafi) and ibrutinib (Imbruvica).

There are currently 36 agents that are FDA approved for at least one indication and can also be prescribed for the treatment of chronic GVHD, Dr. Lee noted.
 

Treatment goals

Dr. Lee laid out six goals for treating patients with chronic GVHD. They include:

• Controlling current signs and symptoms, measured by response rates and patient-reported outcomes
• Preventing further tissue and organ damage
• Minimizing toxicity
• Maintaining graft-versus-tumor effect
• Achieving graft tolerance and stopping immunosuppression
• Decreasing nonrelapse mortality and improving survival

Active trials

Dr. Lee identified 33 trials with chronic GVHD as an indication that are currently recruiting, and an additional 13 trials that are active but closed to recruiting. The trials can be generally grouped by mechanism of action, and involve agents targeting T-regulatory cells, B cells and/or B-cell receptor (BCR) signaling, monocytes/macrophages, costimulatory blockage, a proteasome inhibition, Janus kinase (JAK) 1/2 inhibitors, ROCK2 inhibitors, hedgehog pathway inhibition, cellular therapy, and organ-targeted therapy.

Most of the trials have overall response rate as the primary endpoint, and all but five are currently in phase 1 or 2. The currently active phase 3 trials include two with ibrutinib, one with the investigational agent itacitinib, one with ruxolitinib, and one with mesenchymal stem cells.

“I’ll note that, when results are reported, the denominator really matters for the overall response rate, especially if you’re talking about small trials, because if you require the patient to be treated with an agent for a certain period of time, and you take out all the people who didn’t make it to that time point, then your overall response rate looks better,” she said.
 

BTK inhibitors

The first-in-class Bruton tyrosine kinase (BTK) inhibitor ibrutinib was the first and thus far only agent approved by the Food and Drug Administration for chronic GVHD. The approval was based on a single-arm, multicenter trial with 42 patients.

The ORR in this trial was 69%, consisting of 31% complete responses and 38% partial responses, with a duration of response longer than 10 months in slightly more than half of all patients. In all, 24% of patients had improvement of symptoms in two consecutive visits, and 29% continued on ibrutinib at the time of the primary analysis in 2017.

Based on these promising results, acalabrutinib, which is more potent and selective for BTK than ibrutinib, with no effect on either platelets or natural killer cells, is currently under investigation in a phase 2 trial in 50 patients at a dose of 100 mg orally twice daily.
 

JAK1/2 inhibition

The JAK1 inhibitor itacitinib failed to meet its primary ORR endpoint in the phase 3 GRAVITAS-301 study, according to a press release, but the manufacturer (Incyte) said that it is continuing its commitment to JAK inhibitors with ruxolitinib, which has shown activity against acute, steroid-refractory GVHD, and is being explored for prevention of chronic GVHD in the randomized, phase 3 REACH3 study.

The trial met its primary endpoint for a higher ORR at week 24 with ruxolitinib versus best available therapy, at 49.7% versus 25.6%, respectively, which translated into an odds ratio for response with the JAK inhibitor of 2.99 (P < .0001).
 

Selective T-cell expansion

Efavaleukin alfa is an IL-2-mutated protein (mutein), with a mutation in the IL-2RB-binding portion of IL-2 causing increased selectivity for regulatory T-cell expansion. It is bound to an IgG-Fc domain that is itself mutated, with reduced Fc receptor binding and IgG effector function to give it a longer half life. This agent is being studied in a phase 1/2 trial in a subcutaneous formulation delivered every 1 or 2 weeks to 68 patients.

Monocyte/macrophage depletion

Axatilimab is a high-affinity antibody targeting colony stimulating factor–1 receptor (CSF-1R) expressed on monocytes and macrophages. By blocking CSF-1R, it depletes circulation of nonclassical monocytes and prevents the differentiation and survival of M2 macrophages in tissue.

It is currently being investigated 30 patients in a phase 1/2 study in an intravenous formulation delivered over 30 minutes every 2-4 weeks.
 

Hedgehog pathway inhibition

There is evidence suggesting that hedgehog pathway inhibition can lessen fibrosis. Glasdegib (Daurismo) a potent selective oral inhibitor of the hedgehog signaling pathway, is approved for use with low-dose cytarabine for patients with newly diagnosed acute myeloid leukemia aged older than 75 years or have comorbidities precluding intensive chemotherapy.

This agent is associated with drug intolerance because of muscle spasms, dysgeusia, and alopecia, however.

The drug is currently in phase 1/2 at a dose of 50 mg orally per day in 20 patients.
 

ROCK2 inhibition

Belumosudil (formerly KD025) “appears to rebalance the immune system,” Dr. Lee said. Investigators think that the drug dampens an autoaggressive inflammatory response by selective inhibition of ROCK2.

This drug has been studied in a dose-escalation study and a phase 2 trial, in which 132 participants were randomized to receive belumosudil 200 mg either once or twice daily.

At a median follow-up of 8 months, the ORR with belumosudil 200 mg once and twice daily was 73% and 74%, respectively. Similar results were seen in patients who had previously received either ruxolitinib or ibrutinib. High response rates were seen in patients with severe chronic GVHD, involvement of four or more organs and a refractory response to their last line of therapy.
 

Hard-to-manage patients

“We’re very hopeful for many of these agents, but we have to acknowledge that there are still many management dilemmas, patients that we just don’t really know what to do with,” Dr. Lee said. “These include patients who have bad sclerosis and fasciitis, nonhealing skin ulcers, bronchiolitis obliterans, serositis that can be very difficult to manage, severe keratoconjunctivitis that can be eyesight threatening, nonhealing mouth ulcers, esophageal structures, and always patients who have frequent infections.

“We are hopeful that some these agents will be useful for our patients who have severe manifestations, but often the number of patients with these manifestations in the trials is too low to say something specific about them,” she added.
 

‘Exciting time’

“It’s an exciting time because there are a lot of different drugs that are being studied for chronic GVHD,” commented Betty Hamilton, MD, a hematologist/oncologist at the Cleveland Clinic.

“I think that where the field is going in terms of treatment is recognizing that chronic GVHD is a pretty heterogeneous disease, and we have to learn even more about the underlying biologic pathways to be able to determine which class of drugs to use and when,” she said in an interview.

She agreed with Dr. Lee that the goals of treating patients with chronic GVHD include improving symptoms and quality, preventing progression, ideally tapering patients off immunosuppression, and achieving a balance between preventing negative consequences of GVHD while maintain the benefits of a graft-versus-leukemia effect.

“In our center, drug choice is based on physician preference and comfort with how often they’ve used the drug, patients’ comorbidities, toxicities of the drug, and logistical considerations,” Dr. Hamilton said.

Dr. Lee disclosed consulting activities for Pfizer and Kadmon, travel and lodging from Amgen, and research funding from those companies and others. Dr. Hamilton disclosed consulting for Syndax and Incyte.

Despite improvements in prevention of graft-versus-host disease, chronic GVHD still occurs in 10%-50% of patients who undergo an allogeneic hematopoietic stem cell transplant, and these patients may require prolonged treatment with multiple lines of therapy, said a hematologist and transplant researcher.

“More effective, less toxic therapies for chronic GVHD are needed,” Stephanie Lee, MD, MPH, from the Fred Hutchinson Cancer Research Center in Seattle said at the Transplant & Cellular Therapies Meetings.

Dr. Lee reviewed clinical trials for chronic GVHD at the meeting held by the American Society for Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research.

Although the incidence of chronic GVHD has gradually declined over the last 40 years and both relapse-free and overall survival following a chronic GVHD diagnosis have improved, “for patients who are diagnosed with chronic GVHD, they still will see many lines of therapy and many years of therapy,” she said.

Among 148 patients with chronic GVHD treated at her center, for example, 66% went on to two lines of therapy, 50% went on to three lines, 37% required four lines of therapy, and 20% needed five lines or more.

Salvage therapies for patients with chronic GVHD have evolved away from immunomodulators and immunosuppressants in the early 1990s, toward monoclonal antibodies such as rituximab in the early 2000s, to interleukin-2 and to tyrosine kinase inhibitors such as ruxolitinib (Jakafi) and ibrutinib (Imbruvica).

There are currently 36 agents that are FDA approved for at least one indication and can also be prescribed for the treatment of chronic GVHD, Dr. Lee noted.
 

Treatment goals

Dr. Lee laid out six goals for treating patients with chronic GVHD. They include:

• Controlling current signs and symptoms, measured by response rates and patient-reported outcomes
• Preventing further tissue and organ damage
• Minimizing toxicity
• Maintaining graft-versus-tumor effect
• Achieving graft tolerance and stopping immunosuppression
• Decreasing nonrelapse mortality and improving survival

Active trials

Dr. Lee identified 33 trials with chronic GVHD as an indication that are currently recruiting, and an additional 13 trials that are active but closed to recruiting. The trials can be generally grouped by mechanism of action, and involve agents targeting T-regulatory cells, B cells and/or B-cell receptor (BCR) signaling, monocytes/macrophages, costimulatory blockage, a proteasome inhibition, Janus kinase (JAK) 1/2 inhibitors, ROCK2 inhibitors, hedgehog pathway inhibition, cellular therapy, and organ-targeted therapy.

Most of the trials have overall response rate as the primary endpoint, and all but five are currently in phase 1 or 2. The currently active phase 3 trials include two with ibrutinib, one with the investigational agent itacitinib, one with ruxolitinib, and one with mesenchymal stem cells.

“I’ll note that, when results are reported, the denominator really matters for the overall response rate, especially if you’re talking about small trials, because if you require the patient to be treated with an agent for a certain period of time, and you take out all the people who didn’t make it to that time point, then your overall response rate looks better,” she said.
 

BTK inhibitors

The first-in-class Bruton tyrosine kinase (BTK) inhibitor ibrutinib was the first and thus far only agent approved by the Food and Drug Administration for chronic GVHD. The approval was based on a single-arm, multicenter trial with 42 patients.

The ORR in this trial was 69%, consisting of 31% complete responses and 38% partial responses, with a duration of response longer than 10 months in slightly more than half of all patients. In all, 24% of patients had improvement of symptoms in two consecutive visits, and 29% continued on ibrutinib at the time of the primary analysis in 2017.

Based on these promising results, acalabrutinib, which is more potent and selective for BTK than ibrutinib, with no effect on either platelets or natural killer cells, is currently under investigation in a phase 2 trial in 50 patients at a dose of 100 mg orally twice daily.
 

JAK1/2 inhibition

The JAK1 inhibitor itacitinib failed to meet its primary ORR endpoint in the phase 3 GRAVITAS-301 study, according to a press release, but the manufacturer (Incyte) said that it is continuing its commitment to JAK inhibitors with ruxolitinib, which has shown activity against acute, steroid-refractory GVHD, and is being explored for prevention of chronic GVHD in the randomized, phase 3 REACH3 study.

The trial met its primary endpoint for a higher ORR at week 24 with ruxolitinib versus best available therapy, at 49.7% versus 25.6%, respectively, which translated into an odds ratio for response with the JAK inhibitor of 2.99 (P < .0001).
 

Selective T-cell expansion

Efavaleukin alfa is an IL-2-mutated protein (mutein), with a mutation in the IL-2RB-binding portion of IL-2 causing increased selectivity for regulatory T-cell expansion. It is bound to an IgG-Fc domain that is itself mutated, with reduced Fc receptor binding and IgG effector function to give it a longer half life. This agent is being studied in a phase 1/2 trial in a subcutaneous formulation delivered every 1 or 2 weeks to 68 patients.

Monocyte/macrophage depletion

Axatilimab is a high-affinity antibody targeting colony stimulating factor–1 receptor (CSF-1R) expressed on monocytes and macrophages. By blocking CSF-1R, it depletes circulation of nonclassical monocytes and prevents the differentiation and survival of M2 macrophages in tissue.

It is currently being investigated 30 patients in a phase 1/2 study in an intravenous formulation delivered over 30 minutes every 2-4 weeks.
 

Hedgehog pathway inhibition

There is evidence suggesting that hedgehog pathway inhibition can lessen fibrosis. Glasdegib (Daurismo) a potent selective oral inhibitor of the hedgehog signaling pathway, is approved for use with low-dose cytarabine for patients with newly diagnosed acute myeloid leukemia aged older than 75 years or have comorbidities precluding intensive chemotherapy.

This agent is associated with drug intolerance because of muscle spasms, dysgeusia, and alopecia, however.

The drug is currently in phase 1/2 at a dose of 50 mg orally per day in 20 patients.
 

ROCK2 inhibition

Belumosudil (formerly KD025) “appears to rebalance the immune system,” Dr. Lee said. Investigators think that the drug dampens an autoaggressive inflammatory response by selective inhibition of ROCK2.

This drug has been studied in a dose-escalation study and a phase 2 trial, in which 132 participants were randomized to receive belumosudil 200 mg either once or twice daily.

At a median follow-up of 8 months, the ORR with belumosudil 200 mg once and twice daily was 73% and 74%, respectively. Similar results were seen in patients who had previously received either ruxolitinib or ibrutinib. High response rates were seen in patients with severe chronic GVHD, involvement of four or more organs and a refractory response to their last line of therapy.
 

Hard-to-manage patients

“We’re very hopeful for many of these agents, but we have to acknowledge that there are still many management dilemmas, patients that we just don’t really know what to do with,” Dr. Lee said. “These include patients who have bad sclerosis and fasciitis, nonhealing skin ulcers, bronchiolitis obliterans, serositis that can be very difficult to manage, severe keratoconjunctivitis that can be eyesight threatening, nonhealing mouth ulcers, esophageal structures, and always patients who have frequent infections.

“We are hopeful that some these agents will be useful for our patients who have severe manifestations, but often the number of patients with these manifestations in the trials is too low to say something specific about them,” she added.
 

‘Exciting time’

“It’s an exciting time because there are a lot of different drugs that are being studied for chronic GVHD,” commented Betty Hamilton, MD, a hematologist/oncologist at the Cleveland Clinic.

“I think that where the field is going in terms of treatment is recognizing that chronic GVHD is a pretty heterogeneous disease, and we have to learn even more about the underlying biologic pathways to be able to determine which class of drugs to use and when,” she said in an interview.

She agreed with Dr. Lee that the goals of treating patients with chronic GVHD include improving symptoms and quality, preventing progression, ideally tapering patients off immunosuppression, and achieving a balance between preventing negative consequences of GVHD while maintain the benefits of a graft-versus-leukemia effect.

“In our center, drug choice is based on physician preference and comfort with how often they’ve used the drug, patients’ comorbidities, toxicities of the drug, and logistical considerations,” Dr. Hamilton said.

Dr. Lee disclosed consulting activities for Pfizer and Kadmon, travel and lodging from Amgen, and research funding from those companies and others. Dr. Hamilton disclosed consulting for Syndax and Incyte.

Prescriptions for opioids as a first-line treatment for painful diabetic peripheral neuropathy (DPN) outnumbered those for other medications between 2014 and 2018, despite the fact that the former is not recommended, new research indicates.

“We know that for any kind of chronic pain, opioids are not ideal. They’re not very effective for chronic pain in general, and they’re definitely not safe,” senior author Rozalina G. McCoy, MD, an endocrinologist and primary care clinician at the Mayo Clinic in Rochester, Minn., told this news organization.

That’s true even for severe DPN pain or painful exacerbations, she added.

“There’s a myth that opioids are the strongest pain meds possible ... For painful neuropathic pain, duloxetine [Cymbalta], pregabalin [Lyrica], and gabapentin [Neurontin] are the most effective pain medications based on multiple studies and extensive experience using them,” she explained. “But I think the public perception is that opioids are the strongest. When a patient comes with severe pain, I think there’s that kind of gut feeling that if the pain is severe, I need to give opioids.”

What’s more, she noted, “evidence is emerging for other harms, not only the potential for dependency and potential overdose, but also the potential for opioid-induced hyperalgesia. Opioids themselves can cause chronic pain. When we think about using opioids for chronic pain, we are really shooting ourselves in the foot. We’re going to harm patients.”

The American Diabetes Association DPN guidelines essentially say as much, advising opioids only as a tertiary option for refractory pain, she observed.

The new findings, from a retrospective study of Mayo Clinic electronic health data, were published online in JAMA Network Open by Jungwei Fan, PhD, also of Mayo Clinic, and colleagues.


 

Are fewer patients with DPN receiving any treatment now?

The data also reveal that, while opioid prescribing dropped over the study period, there wasn’t a comparable rise in prescriptions of recommended pain medications, suggesting that recent efforts to minimize opioid prescribing may have resulted in less overall treatment of significant pain. (The study had to be stopped in 2018 when Mayo switched to a new electronic health record system, Dr. McCoy explained.)

“The proportion of opioids among new prescriptions has been decreasing. I’m hopeful that the rates are even lower now than they were 2 years ago. What was concerning to me was the proportion of people receiving treatment overall had gone down,” Dr. McCoy noted.

“So, while it’s great that opioids aren’t being used, it’s doubtful that people with DPN are any less symptomatic. So I worry that there’s a proportion of patients who have pain who aren’t getting the treatment they need just because we don’t want to give them opioids. There are other options,” Dr. McCoy said, including nonpharmacologic approaches.
 

Opioids dominated in new-onset DPN prescribing during 2014-2018

The study involved 3,495 adults with newly diagnosed DPN from all three Mayo Clinic locations in Rochester, Minn.; Phoenix, Ariz.; and Jacksonville, Fla. during the period 2014-2018. Of those, 40.2% (1,406) were prescribed a new pain medication after diagnosis. However, that proportion dropped from 45.6% in 2014 to 35.2% in 2018.

The odds of initiating any treatment were significantly greater among patients with depression (odds ratio, 1.61), arthritis (OR, 1.21), and back pain (OR, 1.34), but decreased over time among all patients.

Among those receiving drug treatment, opioids were prescribed to 43.8%, whereas guideline-recommended medications (gabapentin, pregabalin, and serotonin norepinephrine reuptake inhibitors including duloxetine) were prescribed to 42.9%.

Another 20.6% received medications deemed “acceptable” for treating neuropathic pain, including topical analgesics, tricyclic antidepressants, and other anticonvulsants.

Males were significantly more likely than females to receive opioids (OR, 1.26), while individuals diagnosed with comorbid fibromyalgia were less likely (OR, 0.67). Those with comorbid arthritis were less likely to receive recommended DPN medications (OR, 0.76).

Use of opioids was 29% less likely in 2018, compared with 2014, although this difference did not achieve significance. Similarly, use of recommended medications was 25% more likely in 2018, compared with 2014, also not a significant difference.
 

Dr. McCoy offers clinical pearls for treating pain in DPN

Clinically, Dr. McCoy said that she individualizes treatment for painful DPN.

“I tend to use duloxetine if the patient also has a mood disorder including depression or anxiety, because it can also help with that. Gabapentin can also be helpful for radiculopathy or for chronic low-back pain. It can even help with degenerative joint disease like arthritis of the knees. So, you maximize benefit if you use one drug to treat multiple things.”

All three recommended medications are generic now, although pregabalin still tends to be more expensive, she noted. Gabapentin can cause drowsiness, which makes it ideal for a patient with insomnia but much less so for a long-haul truck driver. Duloxetine doesn’t cause sleepiness. Pregabalin can, but less so than gabapentin.  

“I think that’s why it’s so important to talk to your patient and ask how the neuropathy is affecting them. What other comorbidities do they have? What is their life like? I think you have to figure out what drug works for each individual person.”

Importantly, she advised, if one of the three doesn’t work, stop it and try another. “It doesn’t mean that none of these meds work. All three should be tried to see if they give relief.”

Nonpharmacologic measures such as cognitive behavioral therapy, acupuncture, or physical therapy may help some patients as well.

Supplements such as vitamin B₁₂ – which can also help with metformin-induced B₁₂ deficiency – or alpha-lipoic acid may also be worth a try as long as the patient is made aware of potential risks, she noted.

Dr. McCoy hopes to repeat this study using national data. “I don’t think this is isolated to Mayo ... I think it affects all practices,” she said.

Since the study, “we [Mayo Clinic] have implemented practice changes to limit use of opioids for chronic pain ... so I hope it’s getting better. It’s important to be aware of our patterns in prescribing.”

The study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases. Dr. McCoy reported receiving grants from the AARP Quality Measure Innovation program through a collaboration with OptumLabs and the Mayo Clinic’s Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery.
 

A version of this article first appeared on Medscape.com.

Prescriptions for opioids as a first-line treatment for painful diabetic peripheral neuropathy (DPN) outnumbered those for other medications between 2014 and 2018, despite the fact that the former is not recommended, new research indicates.

“We know that for any kind of chronic pain, opioids are not ideal. They’re not very effective for chronic pain in general, and they’re definitely not safe,” senior author Rozalina G. McCoy, MD, an endocrinologist and primary care clinician at the Mayo Clinic in Rochester, Minn., told this news organization.

That’s true even for severe DPN pain or painful exacerbations, she added.

“There’s a myth that opioids are the strongest pain meds possible ... For painful neuropathic pain, duloxetine [Cymbalta], pregabalin [Lyrica], and gabapentin [Neurontin] are the most effective pain medications based on multiple studies and extensive experience using them,” she explained. “But I think the public perception is that opioids are the strongest. When a patient comes with severe pain, I think there’s that kind of gut feeling that if the pain is severe, I need to give opioids.”

What’s more, she noted, “evidence is emerging for other harms, not only the potential for dependency and potential overdose, but also the potential for opioid-induced hyperalgesia. Opioids themselves can cause chronic pain. When we think about using opioids for chronic pain, we are really shooting ourselves in the foot. We’re going to harm patients.”

The American Diabetes Association DPN guidelines essentially say as much, advising opioids only as a tertiary option for refractory pain, she observed.

The new findings, from a retrospective study of Mayo Clinic electronic health data, were published online in JAMA Network Open by Jungwei Fan, PhD, also of Mayo Clinic, and colleagues.


 

Are fewer patients with DPN receiving any treatment now?

The data also reveal that, while opioid prescribing dropped over the study period, there wasn’t a comparable rise in prescriptions of recommended pain medications, suggesting that recent efforts to minimize opioid prescribing may have resulted in less overall treatment of significant pain. (The study had to be stopped in 2018 when Mayo switched to a new electronic health record system, Dr. McCoy explained.)

“The proportion of opioids among new prescriptions has been decreasing. I’m hopeful that the rates are even lower now than they were 2 years ago. What was concerning to me was the proportion of people receiving treatment overall had gone down,” Dr. McCoy noted.

“So, while it’s great that opioids aren’t being used, it’s doubtful that people with DPN are any less symptomatic. So I worry that there’s a proportion of patients who have pain who aren’t getting the treatment they need just because we don’t want to give them opioids. There are other options,” Dr. McCoy said, including nonpharmacologic approaches.
 

Opioids dominated in new-onset DPN prescribing during 2014-2018

The study involved 3,495 adults with newly diagnosed DPN from all three Mayo Clinic locations in Rochester, Minn.; Phoenix, Ariz.; and Jacksonville, Fla. during the period 2014-2018. Of those, 40.2% (1,406) were prescribed a new pain medication after diagnosis. However, that proportion dropped from 45.6% in 2014 to 35.2% in 2018.

The odds of initiating any treatment were significantly greater among patients with depression (odds ratio, 1.61), arthritis (OR, 1.21), and back pain (OR, 1.34), but decreased over time among all patients.

Among those receiving drug treatment, opioids were prescribed to 43.8%, whereas guideline-recommended medications (gabapentin, pregabalin, and serotonin norepinephrine reuptake inhibitors including duloxetine) were prescribed to 42.9%.

Another 20.6% received medications deemed “acceptable” for treating neuropathic pain, including topical analgesics, tricyclic antidepressants, and other anticonvulsants.

Males were significantly more likely than females to receive opioids (OR, 1.26), while individuals diagnosed with comorbid fibromyalgia were less likely (OR, 0.67). Those with comorbid arthritis were less likely to receive recommended DPN medications (OR, 0.76).

Use of opioids was 29% less likely in 2018, compared with 2014, although this difference did not achieve significance. Similarly, use of recommended medications was 25% more likely in 2018, compared with 2014, also not a significant difference.
 

Dr. McCoy offers clinical pearls for treating pain in DPN

Clinically, Dr. McCoy said that she individualizes treatment for painful DPN.

“I tend to use duloxetine if the patient also has a mood disorder including depression or anxiety, because it can also help with that. Gabapentin can also be helpful for radiculopathy or for chronic low-back pain. It can even help with degenerative joint disease like arthritis of the knees. So, you maximize benefit if you use one drug to treat multiple things.”

All three recommended medications are generic now, although pregabalin still tends to be more expensive, she noted. Gabapentin can cause drowsiness, which makes it ideal for a patient with insomnia but much less so for a long-haul truck driver. Duloxetine doesn’t cause sleepiness. Pregabalin can, but less so than gabapentin.  

“I think that’s why it’s so important to talk to your patient and ask how the neuropathy is affecting them. What other comorbidities do they have? What is their life like? I think you have to figure out what drug works for each individual person.”

Importantly, she advised, if one of the three doesn’t work, stop it and try another. “It doesn’t mean that none of these meds work. All three should be tried to see if they give relief.”

Nonpharmacologic measures such as cognitive behavioral therapy, acupuncture, or physical therapy may help some patients as well.

Supplements such as vitamin B₁₂ – which can also help with metformin-induced B₁₂ deficiency – or alpha-lipoic acid may also be worth a try as long as the patient is made aware of potential risks, she noted.

Dr. McCoy hopes to repeat this study using national data. “I don’t think this is isolated to Mayo ... I think it affects all practices,” she said.

Since the study, “we [Mayo Clinic] have implemented practice changes to limit use of opioids for chronic pain ... so I hope it’s getting better. It’s important to be aware of our patterns in prescribing.”

The study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases. Dr. McCoy reported receiving grants from the AARP Quality Measure Innovation program through a collaboration with OptumLabs and the Mayo Clinic’s Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery.
 

A version of this article first appeared on Medscape.com.

Prescriptions for opioids as a first-line treatment for painful diabetic peripheral neuropathy (DPN) outnumbered those for other medications between 2014 and 2018, despite the fact that the former is not recommended, new research indicates.

“We know that for any kind of chronic pain, opioids are not ideal. They’re not very effective for chronic pain in general, and they’re definitely not safe,” senior author Rozalina G. McCoy, MD, an endocrinologist and primary care clinician at the Mayo Clinic in Rochester, Minn., told this news organization.

That’s true even for severe DPN pain or painful exacerbations, she added.

“There’s a myth that opioids are the strongest pain meds possible ... For painful neuropathic pain, duloxetine [Cymbalta], pregabalin [Lyrica], and gabapentin [Neurontin] are the most effective pain medications based on multiple studies and extensive experience using them,” she explained. “But I think the public perception is that opioids are the strongest. When a patient comes with severe pain, I think there’s that kind of gut feeling that if the pain is severe, I need to give opioids.”

What’s more, she noted, “evidence is emerging for other harms, not only the potential for dependency and potential overdose, but also the potential for opioid-induced hyperalgesia. Opioids themselves can cause chronic pain. When we think about using opioids for chronic pain, we are really shooting ourselves in the foot. We’re going to harm patients.”

The American Diabetes Association DPN guidelines essentially say as much, advising opioids only as a tertiary option for refractory pain, she observed.

The new findings, from a retrospective study of Mayo Clinic electronic health data, were published online in JAMA Network Open by Jungwei Fan, PhD, also of Mayo Clinic, and colleagues.


 

Are fewer patients with DPN receiving any treatment now?

The data also reveal that, while opioid prescribing dropped over the study period, there wasn’t a comparable rise in prescriptions of recommended pain medications, suggesting that recent efforts to minimize opioid prescribing may have resulted in less overall treatment of significant pain. (The study had to be stopped in 2018 when Mayo switched to a new electronic health record system, Dr. McCoy explained.)

“The proportion of opioids among new prescriptions has been decreasing. I’m hopeful that the rates are even lower now than they were 2 years ago. What was concerning to me was the proportion of people receiving treatment overall had gone down,” Dr. McCoy noted.

“So, while it’s great that opioids aren’t being used, it’s doubtful that people with DPN are any less symptomatic. So I worry that there’s a proportion of patients who have pain who aren’t getting the treatment they need just because we don’t want to give them opioids. There are other options,” Dr. McCoy said, including nonpharmacologic approaches.
 

Opioids dominated in new-onset DPN prescribing during 2014-2018

The study involved 3,495 adults with newly diagnosed DPN from all three Mayo Clinic locations in Rochester, Minn.; Phoenix, Ariz.; and Jacksonville, Fla. during the period 2014-2018. Of those, 40.2% (1,406) were prescribed a new pain medication after diagnosis. However, that proportion dropped from 45.6% in 2014 to 35.2% in 2018.

The odds of initiating any treatment were significantly greater among patients with depression (odds ratio, 1.61), arthritis (OR, 1.21), and back pain (OR, 1.34), but decreased over time among all patients.

Among those receiving drug treatment, opioids were prescribed to 43.8%, whereas guideline-recommended medications (gabapentin, pregabalin, and serotonin norepinephrine reuptake inhibitors including duloxetine) were prescribed to 42.9%.

Another 20.6% received medications deemed “acceptable” for treating neuropathic pain, including topical analgesics, tricyclic antidepressants, and other anticonvulsants.

Males were significantly more likely than females to receive opioids (OR, 1.26), while individuals diagnosed with comorbid fibromyalgia were less likely (OR, 0.67). Those with comorbid arthritis were less likely to receive recommended DPN medications (OR, 0.76).

Use of opioids was 29% less likely in 2018, compared with 2014, although this difference did not achieve significance. Similarly, use of recommended medications was 25% more likely in 2018, compared with 2014, also not a significant difference.
 

Dr. McCoy offers clinical pearls for treating pain in DPN

Clinically, Dr. McCoy said that she individualizes treatment for painful DPN.

“I tend to use duloxetine if the patient also has a mood disorder including depression or anxiety, because it can also help with that. Gabapentin can also be helpful for radiculopathy or for chronic low-back pain. It can even help with degenerative joint disease like arthritis of the knees. So, you maximize benefit if you use one drug to treat multiple things.”

All three recommended medications are generic now, although pregabalin still tends to be more expensive, she noted. Gabapentin can cause drowsiness, which makes it ideal for a patient with insomnia but much less so for a long-haul truck driver. Duloxetine doesn’t cause sleepiness. Pregabalin can, but less so than gabapentin.  

“I think that’s why it’s so important to talk to your patient and ask how the neuropathy is affecting them. What other comorbidities do they have? What is their life like? I think you have to figure out what drug works for each individual person.”

Importantly, she advised, if one of the three doesn’t work, stop it and try another. “It doesn’t mean that none of these meds work. All three should be tried to see if they give relief.”

Nonpharmacologic measures such as cognitive behavioral therapy, acupuncture, or physical therapy may help some patients as well.

Supplements such as vitamin B₁₂ – which can also help with metformin-induced B₁₂ deficiency – or alpha-lipoic acid may also be worth a try as long as the patient is made aware of potential risks, she noted.

Dr. McCoy hopes to repeat this study using national data. “I don’t think this is isolated to Mayo ... I think it affects all practices,” she said.

Since the study, “we [Mayo Clinic] have implemented practice changes to limit use of opioids for chronic pain ... so I hope it’s getting better. It’s important to be aware of our patterns in prescribing.”

The study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases. Dr. McCoy reported receiving grants from the AARP Quality Measure Innovation program through a collaboration with OptumLabs and the Mayo Clinic’s Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery.
 

A version of this article first appeared on Medscape.com.