The more complaints of excessive force by police reported by neighborhood residents, the more likely it is that Black pregnant people living in that neighborhood will deliver preterm, according to findings from a new study presented Jan. 28 at the virtual Society for Maternal-Fetal Medicine 2021 Annual Pregnancy Meeting.

“We know there are significant racial disparities in preterm birth which aren’t fully explained by traditional risk factors, like being older, having health problems like high blood pressure, or limited income,” Alexa Freedman, PhD, a postdoctoral fellow at NorthShore University HealthSystem and Northwestern University Institute for Policy Research, Evanston, Ill., told this news organization. “This has left many wondering if there are stressors unique to Black individuals that may be involved,” which has led to past research on the association of preterm birth with neighborhood segregation and historical “redlining” practices.

Black individuals have a substantially higher rate of preterm birth, compared with all other racial and ethnic groups in the US: 13.8% of Black infants born between 2016 and 2018 were preterm, compared with 11.6% among Native Americans – the next highest group – and 9.1% among White women.

“Studies have shown that psychosocial stress contributes to preterm birth disparities, potentially through several physiologic pathways that impact pregnancy outcomes,” Dr. Freedman told attendees. “Pregnant Black individuals have been reported to experience greater psychosocial stress regardless of socioeconomic status, possibly secondary to experiences of racism and discrimination.”

Though past research has examined neighborhood disadvantage and violence as stressors potentially contributing to preterm birth, little data exist on police–community relationships or police violence and pregnancy outcomes, despite being a “particularly salient stressor for Black individuals,” Dr. Freedman said. “Among pregnant Black individuals, prenatal depression has been correlated with concern about negative interactions between youth in their community and police.” To cite one example of the prevalence of racial bias in policing, she noted that “Chicago police are almost 10 times more likely to use force when interacting with a Black individual as compared [with] a White individual.”

The researchers therefore sought to determine whether a relationship existed between preterm birth rates and complaints regarding use of excessive force by police in the same neighborhood. They compiled records on all singleton live births from one Chicago hospital between March 2008 and March 2018, excluding those who lived outside Chicago, had a missing address, listed their race as “other,” or lacked data for specific other confounders.
 

Assessing police complaints within census blocks

The researchers obtained data on police complaints in Chicago from the Invisible Institute’s Citizen Police Data Project. They focused only on complaints of excessive use of force, “such as unnecessary physical contact and unnecessary display of a weapon,” Dr. Freedman said. They considered a person exposed in the neighborhood if a complaint was reported in her census block in the year leading up to birth. During their study period, more than 6,000 complaints of excessive force were reported across an estimated 70% of the blocks.

The study population had an average age of 31 and included 59.5% White, 12% Black, 20% Hispanic, and 8.5% Asian people. Just over half the pregnancies (55%) were first-time pregnancies, and 3.3% of the population had a history of preterm birth (before 37 weeks). The researchers also gathered data to adjust for the study population’s:

• Age
• Parity (number of times the woman has given birth).
• Population size of census block.
• Exposure to a homicide on the block in the year leading up to birth.
• Socioeconomic status by block (based on a composite of median home value, median income, percentage of a high school diploma, and percentage employed).

“Those who lived in a block with an excessive force complaint were more likely to be Black, more likely to deliver preterm, and more likely to be exposed to homicide,” Dr. Freedman told attendees.

The proportion of pregnant women exposed to police complaints was 15.8%, and 10.2% lived in neighborhoods where a homicide occurred in the year leading up to birth. Within the group exposed to a homicide, 16.5% lived in a neighborhood with an excessive force complaint and 9.1% did not.

Overall, 8.1% of the population gave birth preterm. When stratified by whether or not they lived in a block with an excessive force complaint, the researchers found the proportion of preterm births was higher among those who did than those who did not (9.3% vs. 7.8%).

Both before and after adjusting for confounders, Black people were the only racial/ethnic group who had a significantly increased risk of preterm birth if they lived on a block with a complaint. They were nearly 30% more likely to deliver preterm if an excessive force complaint had been reported nearby (odds ratio, 1.29). The odds of preterm birth were slightly elevated for White people and slightly reduced for Hispanic and Asian people, but none of those associations reached significance.

In a sensitivity analysis comparing 189 Black individuals to themselves, the researchers compared those who had one preterm birth and one term birth. They found that the preterm birth was 32% more likely to occur in a year when an excessive force complaint was filed after adjusting for age and birth order (OR, 1.32; 95% confidence interval, 0.82-2.13).

“Police violence reflects just one component of structural racism,” Dr. Freedman said in an interview. “Our findings highlight the need to more thoroughly consider how these systemic and structural factors contribute to disparities in maternal and fetal health.”
 

Clinical and policy implications

The clinical implications of these findings focus on the need for obstetric clinical teams to understand patients’ stressors and to provide support and resources, according to Dr. Freedman’s mentor, Ann Borders, MD, MSc, MPH, a maternal-fetal medicine physician at NorthShore and Evanston Hospital and a clinical associate professor at the University of Chicago Pritzker School of Medicine.

“Potential strategies include training on improved listening and respectful patient-centered care, such as provided by the CDC Hear Her campaign, and consideration of universal social determinants of health screening during obstetric care,” Dr. Borders told this news organization..

Though the study included a large sample size and allowed the researchers to control for individual and neighborhood characteristics, Dr. Freedman acknowledged that census blocks may or may not correlate with the way individuals define their own neighborhoods. They also didn’t have the data to assess the quality of prenatal care or the type of preterm birth, but they are developing a qualitative study to determine the best ways of measuring exposure to police violence.

In addition, the researchers’ reliance only on formal police complaints could have underestimated prevalence of excessive force, and the study did not take into account people’s direct experience with police violence; police violence that occurs within a person’s social network; or police violence widely covered in the news. 

It wasn’t possible for the researchers to verify whether excessive force actually occurred or whether the force might have been justified, and it instead relied on the fact that someone lodged a complaint because he or she perceived the action as excessive.

Allison Bryant Mantha, MD, MPH, vice chair for Quality, Equity, and Safety at Massachusetts General Hospital in Boston and a board member of SMFM, said she was impressed with the adjustment of homicide exposure as a proxy for neighborhood crime.

“Many might assume that reports of police misconduct might be a marker for a ‘dangerous neighborhood,’ and it was thoughtful of the authors to adjust their analyses for exposure to crime to demonstrate that, even above and beyond crime, reports of police misconduct seem to be associated with adverse outcomes,” Dr. Bryant Mantha, who moderated the session, said in an interview.

Confronting this issue goes beyond what clinicians can do on their own, Dr. Bryant Mantha suggested.

“The greatest change will come with addressing the structural racism that underlies differential exposure to police misconduct in communities in the first place,” she said. “Concurrent with this, however, clinicians may consider adding in an assessment of neighborhood characteristics to include reports of police misconduct as they screen for other social determinants of health. While we do not have intervention studies to demonstrate efficacy, it is not a huge leap to imagine that recognition of this burden in individuals’ lives, plus offering ways to manage stress or seek redress, could be of benefit.”

The research was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the National Institute on Minority Health and Health Disparities, and the Northwestern Medicine Enterprise Data Warehouse Pilot Data Program. Dr. Freedman, Dr. Borders, and Dr. Bryant Mantha have disclosed no relevant financial relationships.

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

The more complaints of excessive force by police reported by neighborhood residents, the more likely it is that Black pregnant people living in that neighborhood will deliver preterm, according to findings from a new study presented Jan. 28 at the virtual Society for Maternal-Fetal Medicine 2021 Annual Pregnancy Meeting.

“We know there are significant racial disparities in preterm birth which aren’t fully explained by traditional risk factors, like being older, having health problems like high blood pressure, or limited income,” Alexa Freedman, PhD, a postdoctoral fellow at NorthShore University HealthSystem and Northwestern University Institute for Policy Research, Evanston, Ill., told this news organization. “This has left many wondering if there are stressors unique to Black individuals that may be involved,” which has led to past research on the association of preterm birth with neighborhood segregation and historical “redlining” practices.

Black individuals have a substantially higher rate of preterm birth, compared with all other racial and ethnic groups in the US: 13.8% of Black infants born between 2016 and 2018 were preterm, compared with 11.6% among Native Americans – the next highest group – and 9.1% among White women.

“Studies have shown that psychosocial stress contributes to preterm birth disparities, potentially through several physiologic pathways that impact pregnancy outcomes,” Dr. Freedman told attendees. “Pregnant Black individuals have been reported to experience greater psychosocial stress regardless of socioeconomic status, possibly secondary to experiences of racism and discrimination.”

Though past research has examined neighborhood disadvantage and violence as stressors potentially contributing to preterm birth, little data exist on police–community relationships or police violence and pregnancy outcomes, despite being a “particularly salient stressor for Black individuals,” Dr. Freedman said. “Among pregnant Black individuals, prenatal depression has been correlated with concern about negative interactions between youth in their community and police.” To cite one example of the prevalence of racial bias in policing, she noted that “Chicago police are almost 10 times more likely to use force when interacting with a Black individual as compared [with] a White individual.”

The researchers therefore sought to determine whether a relationship existed between preterm birth rates and complaints regarding use of excessive force by police in the same neighborhood. They compiled records on all singleton live births from one Chicago hospital between March 2008 and March 2018, excluding those who lived outside Chicago, had a missing address, listed their race as “other,” or lacked data for specific other confounders.
 

Assessing police complaints within census blocks

The researchers obtained data on police complaints in Chicago from the Invisible Institute’s Citizen Police Data Project. They focused only on complaints of excessive use of force, “such as unnecessary physical contact and unnecessary display of a weapon,” Dr. Freedman said. They considered a person exposed in the neighborhood if a complaint was reported in her census block in the year leading up to birth. During their study period, more than 6,000 complaints of excessive force were reported across an estimated 70% of the blocks.

The study population had an average age of 31 and included 59.5% White, 12% Black, 20% Hispanic, and 8.5% Asian people. Just over half the pregnancies (55%) were first-time pregnancies, and 3.3% of the population had a history of preterm birth (before 37 weeks). The researchers also gathered data to adjust for the study population’s:

• Age
• Parity (number of times the woman has given birth).
• Population size of census block.
• Exposure to a homicide on the block in the year leading up to birth.
• Socioeconomic status by block (based on a composite of median home value, median income, percentage of a high school diploma, and percentage employed).

“Those who lived in a block with an excessive force complaint were more likely to be Black, more likely to deliver preterm, and more likely to be exposed to homicide,” Dr. Freedman told attendees.

The proportion of pregnant women exposed to police complaints was 15.8%, and 10.2% lived in neighborhoods where a homicide occurred in the year leading up to birth. Within the group exposed to a homicide, 16.5% lived in a neighborhood with an excessive force complaint and 9.1% did not.

Overall, 8.1% of the population gave birth preterm. When stratified by whether or not they lived in a block with an excessive force complaint, the researchers found the proportion of preterm births was higher among those who did than those who did not (9.3% vs. 7.8%).

Both before and after adjusting for confounders, Black people were the only racial/ethnic group who had a significantly increased risk of preterm birth if they lived on a block with a complaint. They were nearly 30% more likely to deliver preterm if an excessive force complaint had been reported nearby (odds ratio, 1.29). The odds of preterm birth were slightly elevated for White people and slightly reduced for Hispanic and Asian people, but none of those associations reached significance.

In a sensitivity analysis comparing 189 Black individuals to themselves, the researchers compared those who had one preterm birth and one term birth. They found that the preterm birth was 32% more likely to occur in a year when an excessive force complaint was filed after adjusting for age and birth order (OR, 1.32; 95% confidence interval, 0.82-2.13).

“Police violence reflects just one component of structural racism,” Dr. Freedman said in an interview. “Our findings highlight the need to more thoroughly consider how these systemic and structural factors contribute to disparities in maternal and fetal health.”
 

Clinical and policy implications

The clinical implications of these findings focus on the need for obstetric clinical teams to understand patients’ stressors and to provide support and resources, according to Dr. Freedman’s mentor, Ann Borders, MD, MSc, MPH, a maternal-fetal medicine physician at NorthShore and Evanston Hospital and a clinical associate professor at the University of Chicago Pritzker School of Medicine.

“Potential strategies include training on improved listening and respectful patient-centered care, such as provided by the CDC Hear Her campaign, and consideration of universal social determinants of health screening during obstetric care,” Dr. Borders told this news organization..

Though the study included a large sample size and allowed the researchers to control for individual and neighborhood characteristics, Dr. Freedman acknowledged that census blocks may or may not correlate with the way individuals define their own neighborhoods. They also didn’t have the data to assess the quality of prenatal care or the type of preterm birth, but they are developing a qualitative study to determine the best ways of measuring exposure to police violence.

In addition, the researchers’ reliance only on formal police complaints could have underestimated prevalence of excessive force, and the study did not take into account people’s direct experience with police violence; police violence that occurs within a person’s social network; or police violence widely covered in the news. 

It wasn’t possible for the researchers to verify whether excessive force actually occurred or whether the force might have been justified, and it instead relied on the fact that someone lodged a complaint because he or she perceived the action as excessive.

Allison Bryant Mantha, MD, MPH, vice chair for Quality, Equity, and Safety at Massachusetts General Hospital in Boston and a board member of SMFM, said she was impressed with the adjustment of homicide exposure as a proxy for neighborhood crime.

“Many might assume that reports of police misconduct might be a marker for a ‘dangerous neighborhood,’ and it was thoughtful of the authors to adjust their analyses for exposure to crime to demonstrate that, even above and beyond crime, reports of police misconduct seem to be associated with adverse outcomes,” Dr. Bryant Mantha, who moderated the session, said in an interview.

Confronting this issue goes beyond what clinicians can do on their own, Dr. Bryant Mantha suggested.

“The greatest change will come with addressing the structural racism that underlies differential exposure to police misconduct in communities in the first place,” she said. “Concurrent with this, however, clinicians may consider adding in an assessment of neighborhood characteristics to include reports of police misconduct as they screen for other social determinants of health. While we do not have intervention studies to demonstrate efficacy, it is not a huge leap to imagine that recognition of this burden in individuals’ lives, plus offering ways to manage stress or seek redress, could be of benefit.”

The research was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the National Institute on Minority Health and Health Disparities, and the Northwestern Medicine Enterprise Data Warehouse Pilot Data Program. Dr. Freedman, Dr. Borders, and Dr. Bryant Mantha have disclosed no relevant financial relationships.

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

The more complaints of excessive force by police reported by neighborhood residents, the more likely it is that Black pregnant people living in that neighborhood will deliver preterm, according to findings from a new study presented Jan. 28 at the virtual Society for Maternal-Fetal Medicine 2021 Annual Pregnancy Meeting.

“We know there are significant racial disparities in preterm birth which aren’t fully explained by traditional risk factors, like being older, having health problems like high blood pressure, or limited income,” Alexa Freedman, PhD, a postdoctoral fellow at NorthShore University HealthSystem and Northwestern University Institute for Policy Research, Evanston, Ill., told this news organization. “This has left many wondering if there are stressors unique to Black individuals that may be involved,” which has led to past research on the association of preterm birth with neighborhood segregation and historical “redlining” practices.

Black individuals have a substantially higher rate of preterm birth, compared with all other racial and ethnic groups in the US: 13.8% of Black infants born between 2016 and 2018 were preterm, compared with 11.6% among Native Americans – the next highest group – and 9.1% among White women.

“Studies have shown that psychosocial stress contributes to preterm birth disparities, potentially through several physiologic pathways that impact pregnancy outcomes,” Dr. Freedman told attendees. “Pregnant Black individuals have been reported to experience greater psychosocial stress regardless of socioeconomic status, possibly secondary to experiences of racism and discrimination.”

Though past research has examined neighborhood disadvantage and violence as stressors potentially contributing to preterm birth, little data exist on police–community relationships or police violence and pregnancy outcomes, despite being a “particularly salient stressor for Black individuals,” Dr. Freedman said. “Among pregnant Black individuals, prenatal depression has been correlated with concern about negative interactions between youth in their community and police.” To cite one example of the prevalence of racial bias in policing, she noted that “Chicago police are almost 10 times more likely to use force when interacting with a Black individual as compared [with] a White individual.”

The researchers therefore sought to determine whether a relationship existed between preterm birth rates and complaints regarding use of excessive force by police in the same neighborhood. They compiled records on all singleton live births from one Chicago hospital between March 2008 and March 2018, excluding those who lived outside Chicago, had a missing address, listed their race as “other,” or lacked data for specific other confounders.
 

Assessing police complaints within census blocks

The researchers obtained data on police complaints in Chicago from the Invisible Institute’s Citizen Police Data Project. They focused only on complaints of excessive use of force, “such as unnecessary physical contact and unnecessary display of a weapon,” Dr. Freedman said. They considered a person exposed in the neighborhood if a complaint was reported in her census block in the year leading up to birth. During their study period, more than 6,000 complaints of excessive force were reported across an estimated 70% of the blocks.

The study population had an average age of 31 and included 59.5% White, 12% Black, 20% Hispanic, and 8.5% Asian people. Just over half the pregnancies (55%) were first-time pregnancies, and 3.3% of the population had a history of preterm birth (before 37 weeks). The researchers also gathered data to adjust for the study population’s:

• Age
• Parity (number of times the woman has given birth).
• Population size of census block.
• Exposure to a homicide on the block in the year leading up to birth.
• Socioeconomic status by block (based on a composite of median home value, median income, percentage of a high school diploma, and percentage employed).

“Those who lived in a block with an excessive force complaint were more likely to be Black, more likely to deliver preterm, and more likely to be exposed to homicide,” Dr. Freedman told attendees.

The proportion of pregnant women exposed to police complaints was 15.8%, and 10.2% lived in neighborhoods where a homicide occurred in the year leading up to birth. Within the group exposed to a homicide, 16.5% lived in a neighborhood with an excessive force complaint and 9.1% did not.

Overall, 8.1% of the population gave birth preterm. When stratified by whether or not they lived in a block with an excessive force complaint, the researchers found the proportion of preterm births was higher among those who did than those who did not (9.3% vs. 7.8%).

Both before and after adjusting for confounders, Black people were the only racial/ethnic group who had a significantly increased risk of preterm birth if they lived on a block with a complaint. They were nearly 30% more likely to deliver preterm if an excessive force complaint had been reported nearby (odds ratio, 1.29). The odds of preterm birth were slightly elevated for White people and slightly reduced for Hispanic and Asian people, but none of those associations reached significance.

In a sensitivity analysis comparing 189 Black individuals to themselves, the researchers compared those who had one preterm birth and one term birth. They found that the preterm birth was 32% more likely to occur in a year when an excessive force complaint was filed after adjusting for age and birth order (OR, 1.32; 95% confidence interval, 0.82-2.13).

“Police violence reflects just one component of structural racism,” Dr. Freedman said in an interview. “Our findings highlight the need to more thoroughly consider how these systemic and structural factors contribute to disparities in maternal and fetal health.”
 

Clinical and policy implications

The clinical implications of these findings focus on the need for obstetric clinical teams to understand patients’ stressors and to provide support and resources, according to Dr. Freedman’s mentor, Ann Borders, MD, MSc, MPH, a maternal-fetal medicine physician at NorthShore and Evanston Hospital and a clinical associate professor at the University of Chicago Pritzker School of Medicine.

“Potential strategies include training on improved listening and respectful patient-centered care, such as provided by the CDC Hear Her campaign, and consideration of universal social determinants of health screening during obstetric care,” Dr. Borders told this news organization..

Though the study included a large sample size and allowed the researchers to control for individual and neighborhood characteristics, Dr. Freedman acknowledged that census blocks may or may not correlate with the way individuals define their own neighborhoods. They also didn’t have the data to assess the quality of prenatal care or the type of preterm birth, but they are developing a qualitative study to determine the best ways of measuring exposure to police violence.

In addition, the researchers’ reliance only on formal police complaints could have underestimated prevalence of excessive force, and the study did not take into account people’s direct experience with police violence; police violence that occurs within a person’s social network; or police violence widely covered in the news. 

It wasn’t possible for the researchers to verify whether excessive force actually occurred or whether the force might have been justified, and it instead relied on the fact that someone lodged a complaint because he or she perceived the action as excessive.

Allison Bryant Mantha, MD, MPH, vice chair for Quality, Equity, and Safety at Massachusetts General Hospital in Boston and a board member of SMFM, said she was impressed with the adjustment of homicide exposure as a proxy for neighborhood crime.

“Many might assume that reports of police misconduct might be a marker for a ‘dangerous neighborhood,’ and it was thoughtful of the authors to adjust their analyses for exposure to crime to demonstrate that, even above and beyond crime, reports of police misconduct seem to be associated with adverse outcomes,” Dr. Bryant Mantha, who moderated the session, said in an interview.

Confronting this issue goes beyond what clinicians can do on their own, Dr. Bryant Mantha suggested.

“The greatest change will come with addressing the structural racism that underlies differential exposure to police misconduct in communities in the first place,” she said. “Concurrent with this, however, clinicians may consider adding in an assessment of neighborhood characteristics to include reports of police misconduct as they screen for other social determinants of health. While we do not have intervention studies to demonstrate efficacy, it is not a huge leap to imagine that recognition of this burden in individuals’ lives, plus offering ways to manage stress or seek redress, could be of benefit.”

The research was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the National Institute on Minority Health and Health Disparities, and the Northwestern Medicine Enterprise Data Warehouse Pilot Data Program. Dr. Freedman, Dr. Borders, and Dr. Bryant Mantha have disclosed no relevant financial relationships.

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

Read this supplement to Rheumatology News here.

• Synovial biopsy findings drive precision medicine closer to the clinic
• Ready for PRIME time? Newly identified cells predict flares
• Rheumatologists’ prescriptions of biosimilars stagnate
• Methotrexate in terms of ILD concerns, poor adherence, and low-dose AEs 10-13 TNF inhibitors linked to risk for inflammatory CNS events
• Hypersensitivity reactions to biologics differentiated
• Repeat latent TB testing focuses on new risks

Read More Now

Read this supplement to Rheumatology News here.

• Synovial biopsy findings drive precision medicine closer to the clinic
• Ready for PRIME time? Newly identified cells predict flares
• Rheumatologists’ prescriptions of biosimilars stagnate
• Methotrexate in terms of ILD concerns, poor adherence, and low-dose AEs 10-13 TNF inhibitors linked to risk for inflammatory CNS events
• Hypersensitivity reactions to biologics differentiated
• Repeat latent TB testing focuses on new risks

Read More Now

Read this supplement to Rheumatology News here.

• Synovial biopsy findings drive precision medicine closer to the clinic
• Ready for PRIME time? Newly identified cells predict flares
• Rheumatologists’ prescriptions of biosimilars stagnate
• Methotrexate in terms of ILD concerns, poor adherence, and low-dose AEs 10-13 TNF inhibitors linked to risk for inflammatory CNS events
• Hypersensitivity reactions to biologics differentiated
• Repeat latent TB testing focuses on new risks

Read More Now

Long term CML follow up clinical trials are quite important tool to monitor the late or new adverse side effects as well as to conform the efficacy in the long run of the drug tested. However, there are not so many examples on CML outside the IRIS trial. Recently, Kantarjian and collaborators had published the 10 years follow up on the ENESTnd trial that compared the use of two doses of nilotinib (300md bid and 400 mg bid) against imatinib (400mg qd). Once again, the study showed a higher cumulative molecular response rates (MMR: 77% vs 79% vs 62% and MR4.5:61% vs61% vs 39%) that translated in a higher proportion of patient candidates for TFR (48% vs 47% vs 29%). Furthermore, nilotinib was associated to lower rates of disease progression compare with imatinib. As previously described there were no differences in terms of PFS or OS between the three arms. In terms of toxicity, although the overall adverse effects were similar, a higher incidence of cardiovascular events were reported (16% vs 23% vs 3%). The incidence of these CVE on the nilotinib arm continue to occur at the same rate each year and were more associated with high and intermediate Framingham risk. Overall, the trial supports the use of nilotinib 300mg twice daily as front line therapy for CML for optimal long terms outcomes with a positive benefit-risk in the context of TFR as treatment goal.

One of the important aspects of the CVE secondary to second generation TKIs is the identification of high-risk populations as well as biomarkers that may help to prevent these episodes. In this regard, Italian investigators recently published a study of 369 patients treated with nilotinib where, besides stratification by the new coronary risk evaluation (SCORE), they measure the lipids levels at various times point since the initiation of therapy and identify cholesterol greater than 200mg/dL and LDL greater than 70 mg/dL as predictors factor for increased risk of CVE as well as a high SCORE risk. The authors suggest an aggressive follow up on lipids levels in patients taking nilotinib and the incorporation of cholesterol lowering medications.

Although the incidence of CVE has been more classically associated with nilotinib and ponatinib, more recent evidence suggests that the use of second generation TKIs in general can increase the risk of CVE in CML patients in comparison with the general population; however, it is hard to study the contribution of the disease itself. Leong and collaborators recently published a very large retrospective analysis of more than 4,000 CML patients that were age and sex matched with 42,000 controls without CML, showing that the incidence of these events is higher before and after the introduction of TKIs in 2001.

Javier Pinilla-Ibarz, MD, PhD
Senior Member
Lymphoma Section Head and
Director of Immunotherapy
Malignant Hematology Department
H. Lee Moffitt Cancer Center & Research Institute
 

Long term CML follow up clinical trials are quite important tool to monitor the late or new adverse side effects as well as to conform the efficacy in the long run of the drug tested. However, there are not so many examples on CML outside the IRIS trial. Recently, Kantarjian and collaborators had published the 10 years follow up on the ENESTnd trial that compared the use of two doses of nilotinib (300md bid and 400 mg bid) against imatinib (400mg qd). Once again, the study showed a higher cumulative molecular response rates (MMR: 77% vs 79% vs 62% and MR4.5:61% vs61% vs 39%) that translated in a higher proportion of patient candidates for TFR (48% vs 47% vs 29%). Furthermore, nilotinib was associated to lower rates of disease progression compare with imatinib. As previously described there were no differences in terms of PFS or OS between the three arms. In terms of toxicity, although the overall adverse effects were similar, a higher incidence of cardiovascular events were reported (16% vs 23% vs 3%). The incidence of these CVE on the nilotinib arm continue to occur at the same rate each year and were more associated with high and intermediate Framingham risk. Overall, the trial supports the use of nilotinib 300mg twice daily as front line therapy for CML for optimal long terms outcomes with a positive benefit-risk in the context of TFR as treatment goal.

One of the important aspects of the CVE secondary to second generation TKIs is the identification of high-risk populations as well as biomarkers that may help to prevent these episodes. In this regard, Italian investigators recently published a study of 369 patients treated with nilotinib where, besides stratification by the new coronary risk evaluation (SCORE), they measure the lipids levels at various times point since the initiation of therapy and identify cholesterol greater than 200mg/dL and LDL greater than 70 mg/dL as predictors factor for increased risk of CVE as well as a high SCORE risk. The authors suggest an aggressive follow up on lipids levels in patients taking nilotinib and the incorporation of cholesterol lowering medications.

Although the incidence of CVE has been more classically associated with nilotinib and ponatinib, more recent evidence suggests that the use of second generation TKIs in general can increase the risk of CVE in CML patients in comparison with the general population; however, it is hard to study the contribution of the disease itself. Leong and collaborators recently published a very large retrospective analysis of more than 4,000 CML patients that were age and sex matched with 42,000 controls without CML, showing that the incidence of these events is higher before and after the introduction of TKIs in 2001.

Javier Pinilla-Ibarz, MD, PhD
Senior Member
Lymphoma Section Head and
Director of Immunotherapy
Malignant Hematology Department
H. Lee Moffitt Cancer Center & Research Institute
 

Long term CML follow up clinical trials are quite important tool to monitor the late or new adverse side effects as well as to conform the efficacy in the long run of the drug tested. However, there are not so many examples on CML outside the IRIS trial. Recently, Kantarjian and collaborators had published the 10 years follow up on the ENESTnd trial that compared the use of two doses of nilotinib (300md bid and 400 mg bid) against imatinib (400mg qd). Once again, the study showed a higher cumulative molecular response rates (MMR: 77% vs 79% vs 62% and MR4.5:61% vs61% vs 39%) that translated in a higher proportion of patient candidates for TFR (48% vs 47% vs 29%). Furthermore, nilotinib was associated to lower rates of disease progression compare with imatinib. As previously described there were no differences in terms of PFS or OS between the three arms. In terms of toxicity, although the overall adverse effects were similar, a higher incidence of cardiovascular events were reported (16% vs 23% vs 3%). The incidence of these CVE on the nilotinib arm continue to occur at the same rate each year and were more associated with high and intermediate Framingham risk. Overall, the trial supports the use of nilotinib 300mg twice daily as front line therapy for CML for optimal long terms outcomes with a positive benefit-risk in the context of TFR as treatment goal.

One of the important aspects of the CVE secondary to second generation TKIs is the identification of high-risk populations as well as biomarkers that may help to prevent these episodes. In this regard, Italian investigators recently published a study of 369 patients treated with nilotinib where, besides stratification by the new coronary risk evaluation (SCORE), they measure the lipids levels at various times point since the initiation of therapy and identify cholesterol greater than 200mg/dL and LDL greater than 70 mg/dL as predictors factor for increased risk of CVE as well as a high SCORE risk. The authors suggest an aggressive follow up on lipids levels in patients taking nilotinib and the incorporation of cholesterol lowering medications.

Although the incidence of CVE has been more classically associated with nilotinib and ponatinib, more recent evidence suggests that the use of second generation TKIs in general can increase the risk of CVE in CML patients in comparison with the general population; however, it is hard to study the contribution of the disease itself. Leong and collaborators recently published a very large retrospective analysis of more than 4,000 CML patients that were age and sex matched with 42,000 controls without CML, showing that the incidence of these events is higher before and after the introduction of TKIs in 2001.

Javier Pinilla-Ibarz, MD, PhD
Senior Member
Lymphoma Section Head and
Director of Immunotherapy
Malignant Hematology Department
H. Lee Moffitt Cancer Center & Research Institute
 

ANSWER

The correct answer—the false statement—is that SA has no pathologic implications (choice “a”).

DISCUSSION

SAs are usually benign and occur in 10% to 15% of the population (particularly in children). But they can sometimes be a sign of serious disease such as liver failure, with related esophageal varices, especially if > 3 lesions are present.

SAs are caused by a failure in the sphincter muscle surrounding a dilated cutaneous arteriole, which in turn is caused by increased estrogen levels in the blood. This increase can be related to the estrogen in birth control medications or to pregnancy.

A diseased liver, unable to metabolize estrogen properly, can contribute to increased blood levels of estrogen. For example, about one-third of patients with cirrhosis will develop multiple SAs.

SAs are seen only in the distribution of the superior vena cava. This means that—in addition to manifesting on the face—they can also appear on the arms, hands, trunk, and fingers.

Momentarily fading completely when central pressure is applied is a peculiar trait of SAs and is therefore diagnostic.

TREATMENT

While these lesions do, in fact, usually resolve on their own, treatment attempts are usually highly satisfactory. In my experience, destruction by laser ablation is superior to electrodessication, though recurrences are common. At the time of this presentation, the patient and her mother were still pondering the treatment options.

ANSWER

The correct answer—the false statement—is that SA has no pathologic implications (choice “a”).

DISCUSSION

SAs are usually benign and occur in 10% to 15% of the population (particularly in children). But they can sometimes be a sign of serious disease such as liver failure, with related esophageal varices, especially if > 3 lesions are present.

SAs are caused by a failure in the sphincter muscle surrounding a dilated cutaneous arteriole, which in turn is caused by increased estrogen levels in the blood. This increase can be related to the estrogen in birth control medications or to pregnancy.

A diseased liver, unable to metabolize estrogen properly, can contribute to increased blood levels of estrogen. For example, about one-third of patients with cirrhosis will develop multiple SAs.

SAs are seen only in the distribution of the superior vena cava. This means that—in addition to manifesting on the face—they can also appear on the arms, hands, trunk, and fingers.

Momentarily fading completely when central pressure is applied is a peculiar trait of SAs and is therefore diagnostic.

TREATMENT

While these lesions do, in fact, usually resolve on their own, treatment attempts are usually highly satisfactory. In my experience, destruction by laser ablation is superior to electrodessication, though recurrences are common. At the time of this presentation, the patient and her mother were still pondering the treatment options.

ANSWER

The correct answer—the false statement—is that SA has no pathologic implications (choice “a”).

DISCUSSION

SAs are usually benign and occur in 10% to 15% of the population (particularly in children). But they can sometimes be a sign of serious disease such as liver failure, with related esophageal varices, especially if > 3 lesions are present.

SAs are caused by a failure in the sphincter muscle surrounding a dilated cutaneous arteriole, which in turn is caused by increased estrogen levels in the blood. This increase can be related to the estrogen in birth control medications or to pregnancy.

A diseased liver, unable to metabolize estrogen properly, can contribute to increased blood levels of estrogen. For example, about one-third of patients with cirrhosis will develop multiple SAs.

SAs are seen only in the distribution of the superior vena cava. This means that—in addition to manifesting on the face—they can also appear on the arms, hands, trunk, and fingers.

Momentarily fading completely when central pressure is applied is a peculiar trait of SAs and is therefore diagnostic.

TREATMENT

While these lesions do, in fact, usually resolve on their own, treatment attempts are usually highly satisfactory. In my experience, destruction by laser ablation is superior to electrodessication, though recurrences are common. At the time of this presentation, the patient and her mother were still pondering the treatment options.

As Rachna Rawal, MD, was donning her personal protective equipment (PPE), a process that has become deeply ingrained into her muscle memory, a nurse approached her to ask, “Hey, for Mr. Smith, any chance we can time these labs to be done together with his medication administration? We’ve been in and out of that room a few times already.”

As someone who embraces high-value care, this simple suggestion surprised her. What an easy strategy to minimize room entry with full PPE, lab testing, and patient interruptions. That same day, someone else asked, “Do we need overnight vitals?”

COVID-19 has forced hospitalists to reconsider almost every aspect of care. It feels like every decision we make including things we do routinely – labs, vital signs, imaging – needs to be reassessed to determine the actual benefit to the patient balanced against concerns about staff safety, dwindling PPE supplies, and medication reserves. We are all faced with frequently answering the question, “How will this intervention help the patient?” This question lies at the heart of delivering high-value care.

High-value care is providing the best care possible through efficient use of resources, achieving optimal results for each patient. While high-value care has become a prominent focus over the past decade, COVID-19’s high transmissibility without a cure – and associated scarcity of health care resources – have sparked additional discussions on the front lines about promoting patient outcomes while avoiding waste. Clinicians may not have realized that these were high-value care conversations.

The United States’ health care quality and cost crises, worsened in the face of the current pandemic, have been glaringly apparent for years. Our country is spending more money on health care than anywhere else in the world without desired improvements in patient outcomes. A 2019 JAMA study found that 25% of all health care spending, an estimated $760 to $935 billion, is considered waste, and a significant proportion of this waste is due to repetitive care, overuse and unnecessary care in the U.S.¹

Examples of low-value care tests include ordering daily labs in stable medicine inpatients, routine urine electrolytes in acute kidney injury, and folate testing in anemia. The Choosing Wisely^® national campaign, Journal of Hospital Medicine’s “Things We Do For No Reason,” and JAMA Internal Medicine’s “Teachable Moment” series have provided guidance on areas where common testing or interventions may not benefit patient outcomes.

The COVID-19 pandemic has raised questions related to other widely-utilized practices: Can medication times be readjusted to allow only one entry into the room? Will these labs or imaging studies actually change management? Are vital checks every 4 hours needed?

Why did it take the COVID-19 threat to our medical system to force many of us to have these discussions? Despite prior efforts to integrate high-value care into hospital practices, long-standing habits and deep-seeded culture are challenging to overcome. Once clinicians develop practice habits, these behaviors tend to persist throughout their careers.² In many ways, COVID-19 was like hitting a “reset button” as health care professionals were forced to rapidly confront their deeply-ingrained hospital practices and habits. From new protocols for patient rounding to universal masking and social distancing to ground-breaking strategies like awake proning, the response to COVID-19 has represented an unprecedented rapid shift in practice. Previously, consequences of overuse were too downstream or too abstract for clinicians to see in real-time. However, now the ramifications of these choices hit closer to home with obvious potential consequences – like spreading a terrifying virus.

There are three interventions that hospitalists should consider implementing immediately in the COVID-19 era that accelerate us toward high-value care. Routine lab tests, imaging, and overnight vitals represent opportunities to provide patient-centered care while also remaining cognizant of resource utilization.

One area in hospital medicine that has proven challenging to significantly change practice has been routine daily labs. Patients on a general medical inpatient service who are clinically stable generally do not benefit from routine lab work.³ Avoiding these tests does not increase mortality or length of stay in clinically stable patients.³ However, despite this evidence, many patients with COVID-19 and other conditions experience lab draws that are not timed together and are done each morning out of “routine.” Choosing Wisely^® recommendations from the Society of Hospital Medicine encourage clinicians to question routine lab work for COVID-19 patients and to consider batching them, if possible.^3,4 In COVID-19 patients, the risks of not batching tests are magnified, both in terms of the patient-centered experience and for clinician safety. In essence, COVID-19 has pushed us to consider the elements of safety, PPE conservation and other factors, rather than making decisions based solely on their own comfort, convenience, or historical practice.

Clinicians are also reconsidering the necessity of imaging during the pandemic. The “Things We Do For No Reason” article on “Choosing Wisely^® in the COVID-19 era” highlights this well.⁴ It is more important now than ever to decide whether the timing and type of imaging will change management for your patient. Questions to ask include: Can a portable x-ray be used to avoid patient travel and will that CT scan help your patient? A posterior-anterior/lateral x-ray can potentially provide more information depending on the clinical scenario. However, we now need to assess if that extra information is going to impact patient management. Downstream consequences of these decisions include not only risks to the patient but also infectious exposures for staff and others during patient travel.

Lastly, overnight vital sign checks are another intervention we should analyze through this high-value care lens. The Journal of Hospital Medicine released a “Things We Do For No Reason” article about minimizing overnight vitals to promote uninterrupted sleep at night.⁵ Deleterious effects of interrupting the sleep of our patients include delirium and patient dissatisfaction.⁵ Studies have shown the benefits of this approach, yet the shift away from routine overnight vitals has not yet widely occurred.

COVID-19 has pressed us to save PPE and minimize exposure risk; hence, some centers are coordinating the timing of vitals with medication administration times, when feasible. In the stable patient recovering from COVID-19, overnight vitals may not be necessary, particularly if remote monitoring is available. This accomplishes multiple goals: Providing high quality patient care, reducing resource utilization, and minimizing patient nighttime interruptions – all culminating in high-value care.

Even though the COVID-19 pandemic has brought unforeseen emotional, physical, and financial challenges for the health care system and its workers, there may be a silver lining. The pandemic has sparked high-value care discussions, and the urgency of the crisis may be instilling new practices in our daily work. This virus has indeed left a terrible wake of destruction, but may also be a nudge to permanently change our culture of overuse to help us shape the habits of all trainees during this tumultuous time. This experience will hopefully culminate in a culture in which clinicians routinely ask, “How will this intervention help the patient?”
 

Dr. Rawal is clinical assistant professor of medicine, University of Pittsburgh. Dr. Linker is assistant professor of medicine, Mount Sinai Hospital, Icahn School of Medicine at Mount Sinai, New York. Dr. Moriates is associate professor of internal medicine, Dell Medical School at the University of Texas at Austin.

References

1. Shrank W et al. Waste in The US healthcare system. JAMA. 2019;322(15):1501-9.

2. Chen C et al. Spending patterns in region of residency training and subsequent expenditures for care provided by practicing physicians for Medicare beneficiaries. JAMA. 2014;312(22):2385-93.

3. Eaton KP et al. Evidence-based guidelines to eliminate repetitive laboratory testing. JAMA Intern Med. 2017;177(12):1833-9.

4. Cho H et al. Choosing Wisely in the COVID-19 Era: Preventing harm to healthcare workers. J Hosp Med. 2020;15(6):360-2.

5. Orlov N and Arora V. Things we do for no reason: Routine overnight vital sign checks. J Hosp Med. 2020;15(5):272-27.

As Rachna Rawal, MD, was donning her personal protective equipment (PPE), a process that has become deeply ingrained into her muscle memory, a nurse approached her to ask, “Hey, for Mr. Smith, any chance we can time these labs to be done together with his medication administration? We’ve been in and out of that room a few times already.”

As someone who embraces high-value care, this simple suggestion surprised her. What an easy strategy to minimize room entry with full PPE, lab testing, and patient interruptions. That same day, someone else asked, “Do we need overnight vitals?”

COVID-19 has forced hospitalists to reconsider almost every aspect of care. It feels like every decision we make including things we do routinely – labs, vital signs, imaging – needs to be reassessed to determine the actual benefit to the patient balanced against concerns about staff safety, dwindling PPE supplies, and medication reserves. We are all faced with frequently answering the question, “How will this intervention help the patient?” This question lies at the heart of delivering high-value care.

High-value care is providing the best care possible through efficient use of resources, achieving optimal results for each patient. While high-value care has become a prominent focus over the past decade, COVID-19’s high transmissibility without a cure – and associated scarcity of health care resources – have sparked additional discussions on the front lines about promoting patient outcomes while avoiding waste. Clinicians may not have realized that these were high-value care conversations.

The United States’ health care quality and cost crises, worsened in the face of the current pandemic, have been glaringly apparent for years. Our country is spending more money on health care than anywhere else in the world without desired improvements in patient outcomes. A 2019 JAMA study found that 25% of all health care spending, an estimated $760 to $935 billion, is considered waste, and a significant proportion of this waste is due to repetitive care, overuse and unnecessary care in the U.S.¹

Examples of low-value care tests include ordering daily labs in stable medicine inpatients, routine urine electrolytes in acute kidney injury, and folate testing in anemia. The Choosing Wisely^® national campaign, Journal of Hospital Medicine’s “Things We Do For No Reason,” and JAMA Internal Medicine’s “Teachable Moment” series have provided guidance on areas where common testing or interventions may not benefit patient outcomes.

The COVID-19 pandemic has raised questions related to other widely-utilized practices: Can medication times be readjusted to allow only one entry into the room? Will these labs or imaging studies actually change management? Are vital checks every 4 hours needed?

Why did it take the COVID-19 threat to our medical system to force many of us to have these discussions? Despite prior efforts to integrate high-value care into hospital practices, long-standing habits and deep-seeded culture are challenging to overcome. Once clinicians develop practice habits, these behaviors tend to persist throughout their careers.² In many ways, COVID-19 was like hitting a “reset button” as health care professionals were forced to rapidly confront their deeply-ingrained hospital practices and habits. From new protocols for patient rounding to universal masking and social distancing to ground-breaking strategies like awake proning, the response to COVID-19 has represented an unprecedented rapid shift in practice. Previously, consequences of overuse were too downstream or too abstract for clinicians to see in real-time. However, now the ramifications of these choices hit closer to home with obvious potential consequences – like spreading a terrifying virus.

There are three interventions that hospitalists should consider implementing immediately in the COVID-19 era that accelerate us toward high-value care. Routine lab tests, imaging, and overnight vitals represent opportunities to provide patient-centered care while also remaining cognizant of resource utilization.

One area in hospital medicine that has proven challenging to significantly change practice has been routine daily labs. Patients on a general medical inpatient service who are clinically stable generally do not benefit from routine lab work.³ Avoiding these tests does not increase mortality or length of stay in clinically stable patients.³ However, despite this evidence, many patients with COVID-19 and other conditions experience lab draws that are not timed together and are done each morning out of “routine.” Choosing Wisely^® recommendations from the Society of Hospital Medicine encourage clinicians to question routine lab work for COVID-19 patients and to consider batching them, if possible.^3,4 In COVID-19 patients, the risks of not batching tests are magnified, both in terms of the patient-centered experience and for clinician safety. In essence, COVID-19 has pushed us to consider the elements of safety, PPE conservation and other factors, rather than making decisions based solely on their own comfort, convenience, or historical practice.

Clinicians are also reconsidering the necessity of imaging during the pandemic. The “Things We Do For No Reason” article on “Choosing Wisely^® in the COVID-19 era” highlights this well.⁴ It is more important now than ever to decide whether the timing and type of imaging will change management for your patient. Questions to ask include: Can a portable x-ray be used to avoid patient travel and will that CT scan help your patient? A posterior-anterior/lateral x-ray can potentially provide more information depending on the clinical scenario. However, we now need to assess if that extra information is going to impact patient management. Downstream consequences of these decisions include not only risks to the patient but also infectious exposures for staff and others during patient travel.

Lastly, overnight vital sign checks are another intervention we should analyze through this high-value care lens. The Journal of Hospital Medicine released a “Things We Do For No Reason” article about minimizing overnight vitals to promote uninterrupted sleep at night.⁵ Deleterious effects of interrupting the sleep of our patients include delirium and patient dissatisfaction.⁵ Studies have shown the benefits of this approach, yet the shift away from routine overnight vitals has not yet widely occurred.

COVID-19 has pressed us to save PPE and minimize exposure risk; hence, some centers are coordinating the timing of vitals with medication administration times, when feasible. In the stable patient recovering from COVID-19, overnight vitals may not be necessary, particularly if remote monitoring is available. This accomplishes multiple goals: Providing high quality patient care, reducing resource utilization, and minimizing patient nighttime interruptions – all culminating in high-value care.

Even though the COVID-19 pandemic has brought unforeseen emotional, physical, and financial challenges for the health care system and its workers, there may be a silver lining. The pandemic has sparked high-value care discussions, and the urgency of the crisis may be instilling new practices in our daily work. This virus has indeed left a terrible wake of destruction, but may also be a nudge to permanently change our culture of overuse to help us shape the habits of all trainees during this tumultuous time. This experience will hopefully culminate in a culture in which clinicians routinely ask, “How will this intervention help the patient?”
 

Dr. Rawal is clinical assistant professor of medicine, University of Pittsburgh. Dr. Linker is assistant professor of medicine, Mount Sinai Hospital, Icahn School of Medicine at Mount Sinai, New York. Dr. Moriates is associate professor of internal medicine, Dell Medical School at the University of Texas at Austin.

References

1. Shrank W et al. Waste in The US healthcare system. JAMA. 2019;322(15):1501-9.

2. Chen C et al. Spending patterns in region of residency training and subsequent expenditures for care provided by practicing physicians for Medicare beneficiaries. JAMA. 2014;312(22):2385-93.

3. Eaton KP et al. Evidence-based guidelines to eliminate repetitive laboratory testing. JAMA Intern Med. 2017;177(12):1833-9.

4. Cho H et al. Choosing Wisely in the COVID-19 Era: Preventing harm to healthcare workers. J Hosp Med. 2020;15(6):360-2.

5. Orlov N and Arora V. Things we do for no reason: Routine overnight vital sign checks. J Hosp Med. 2020;15(5):272-27.

As Rachna Rawal, MD, was donning her personal protective equipment (PPE), a process that has become deeply ingrained into her muscle memory, a nurse approached her to ask, “Hey, for Mr. Smith, any chance we can time these labs to be done together with his medication administration? We’ve been in and out of that room a few times already.”

As someone who embraces high-value care, this simple suggestion surprised her. What an easy strategy to minimize room entry with full PPE, lab testing, and patient interruptions. That same day, someone else asked, “Do we need overnight vitals?”

COVID-19 has forced hospitalists to reconsider almost every aspect of care. It feels like every decision we make including things we do routinely – labs, vital signs, imaging – needs to be reassessed to determine the actual benefit to the patient balanced against concerns about staff safety, dwindling PPE supplies, and medication reserves. We are all faced with frequently answering the question, “How will this intervention help the patient?” This question lies at the heart of delivering high-value care.

High-value care is providing the best care possible through efficient use of resources, achieving optimal results for each patient. While high-value care has become a prominent focus over the past decade, COVID-19’s high transmissibility without a cure – and associated scarcity of health care resources – have sparked additional discussions on the front lines about promoting patient outcomes while avoiding waste. Clinicians may not have realized that these were high-value care conversations.

The United States’ health care quality and cost crises, worsened in the face of the current pandemic, have been glaringly apparent for years. Our country is spending more money on health care than anywhere else in the world without desired improvements in patient outcomes. A 2019 JAMA study found that 25% of all health care spending, an estimated $760 to $935 billion, is considered waste, and a significant proportion of this waste is due to repetitive care, overuse and unnecessary care in the U.S.¹

Examples of low-value care tests include ordering daily labs in stable medicine inpatients, routine urine electrolytes in acute kidney injury, and folate testing in anemia. The Choosing Wisely^® national campaign, Journal of Hospital Medicine’s “Things We Do For No Reason,” and JAMA Internal Medicine’s “Teachable Moment” series have provided guidance on areas where common testing or interventions may not benefit patient outcomes.

The COVID-19 pandemic has raised questions related to other widely-utilized practices: Can medication times be readjusted to allow only one entry into the room? Will these labs or imaging studies actually change management? Are vital checks every 4 hours needed?

Why did it take the COVID-19 threat to our medical system to force many of us to have these discussions? Despite prior efforts to integrate high-value care into hospital practices, long-standing habits and deep-seeded culture are challenging to overcome. Once clinicians develop practice habits, these behaviors tend to persist throughout their careers.² In many ways, COVID-19 was like hitting a “reset button” as health care professionals were forced to rapidly confront their deeply-ingrained hospital practices and habits. From new protocols for patient rounding to universal masking and social distancing to ground-breaking strategies like awake proning, the response to COVID-19 has represented an unprecedented rapid shift in practice. Previously, consequences of overuse were too downstream or too abstract for clinicians to see in real-time. However, now the ramifications of these choices hit closer to home with obvious potential consequences – like spreading a terrifying virus.

There are three interventions that hospitalists should consider implementing immediately in the COVID-19 era that accelerate us toward high-value care. Routine lab tests, imaging, and overnight vitals represent opportunities to provide patient-centered care while also remaining cognizant of resource utilization.

One area in hospital medicine that has proven challenging to significantly change practice has been routine daily labs. Patients on a general medical inpatient service who are clinically stable generally do not benefit from routine lab work.³ Avoiding these tests does not increase mortality or length of stay in clinically stable patients.³ However, despite this evidence, many patients with COVID-19 and other conditions experience lab draws that are not timed together and are done each morning out of “routine.” Choosing Wisely^® recommendations from the Society of Hospital Medicine encourage clinicians to question routine lab work for COVID-19 patients and to consider batching them, if possible.^3,4 In COVID-19 patients, the risks of not batching tests are magnified, both in terms of the patient-centered experience and for clinician safety. In essence, COVID-19 has pushed us to consider the elements of safety, PPE conservation and other factors, rather than making decisions based solely on their own comfort, convenience, or historical practice.

Clinicians are also reconsidering the necessity of imaging during the pandemic. The “Things We Do For No Reason” article on “Choosing Wisely^® in the COVID-19 era” highlights this well.⁴ It is more important now than ever to decide whether the timing and type of imaging will change management for your patient. Questions to ask include: Can a portable x-ray be used to avoid patient travel and will that CT scan help your patient? A posterior-anterior/lateral x-ray can potentially provide more information depending on the clinical scenario. However, we now need to assess if that extra information is going to impact patient management. Downstream consequences of these decisions include not only risks to the patient but also infectious exposures for staff and others during patient travel.

Lastly, overnight vital sign checks are another intervention we should analyze through this high-value care lens. The Journal of Hospital Medicine released a “Things We Do For No Reason” article about minimizing overnight vitals to promote uninterrupted sleep at night.⁵ Deleterious effects of interrupting the sleep of our patients include delirium and patient dissatisfaction.⁵ Studies have shown the benefits of this approach, yet the shift away from routine overnight vitals has not yet widely occurred.

COVID-19 has pressed us to save PPE and minimize exposure risk; hence, some centers are coordinating the timing of vitals with medication administration times, when feasible. In the stable patient recovering from COVID-19, overnight vitals may not be necessary, particularly if remote monitoring is available. This accomplishes multiple goals: Providing high quality patient care, reducing resource utilization, and minimizing patient nighttime interruptions – all culminating in high-value care.

Even though the COVID-19 pandemic has brought unforeseen emotional, physical, and financial challenges for the health care system and its workers, there may be a silver lining. The pandemic has sparked high-value care discussions, and the urgency of the crisis may be instilling new practices in our daily work. This virus has indeed left a terrible wake of destruction, but may also be a nudge to permanently change our culture of overuse to help us shape the habits of all trainees during this tumultuous time. This experience will hopefully culminate in a culture in which clinicians routinely ask, “How will this intervention help the patient?”
 

Dr. Rawal is clinical assistant professor of medicine, University of Pittsburgh. Dr. Linker is assistant professor of medicine, Mount Sinai Hospital, Icahn School of Medicine at Mount Sinai, New York. Dr. Moriates is associate professor of internal medicine, Dell Medical School at the University of Texas at Austin.

References

1. Shrank W et al. Waste in The US healthcare system. JAMA. 2019;322(15):1501-9.

2. Chen C et al. Spending patterns in region of residency training and subsequent expenditures for care provided by practicing physicians for Medicare beneficiaries. JAMA. 2014;312(22):2385-93.

3. Eaton KP et al. Evidence-based guidelines to eliminate repetitive laboratory testing. JAMA Intern Med. 2017;177(12):1833-9.

4. Cho H et al. Choosing Wisely in the COVID-19 Era: Preventing harm to healthcare workers. J Hosp Med. 2020;15(6):360-2.

5. Orlov N and Arora V. Things we do for no reason: Routine overnight vital sign checks. J Hosp Med. 2020;15(5):272-27.

While 34 million adults in the United States have received a COVID-19 vaccine, children and teenagers are waiting at the back of the line, mostly ineligible for the authorized vaccines. That secondary status is rapidly changing though, as experts expect vaccinations of adolescents to begin by this summer.

The vaccinations can’t come soon enough for parents like Stacy Hillenburg, a developmental therapist in Aurora, Ill., whose 9-year-old son takes immunosuppressants because he had a heart transplant when he was 7 weeks old. Although school-age children aren’t yet included in clinical trials, if her 12- and 13-year-old daughters could get vaccinated, along with both parents, then the family could relax some of the protocols they currently follow to prevent infection.

Whenever they are around other people, even masked and socially distanced, they come home and immediately shower and change their clothes. So far, no one in the family has been infected with COVID, but the anxiety is ever-present. “I can’t wait for it to come out,” Ms. Hillenburg said of a pediatric COVID vaccine. “It will ease my mind so much.”

She isn’t alone in that anticipation. In the fall, the American Academy of Pediatrics and other pediatric vaccine experts urged faster action on pediatric vaccine trials and worried that children would be left behind as adults gained protection from COVID. But recent developments have eased those concerns.

“Over the next couple of months, we will be doing trials in an age-deescalation manner,” with studies moving gradually to younger children, Anthony S. Fauci, MD, chief medical adviser on COVID-19 to the president, said in a coronavirus response team briefing on Jan. 29. “So that hopefully, as we get to the late spring and summer, we will have children being able to be vaccinated.”

Pfizer completed enrollment of 2,259 teens aged 12-15 years in late January and expects to move forward with a separate pediatric trial of children aged 5-11 years by this spring, Keanna Ghazvini, senior associate for global media relations at Pfizer, said in an interview.

Enrollment in Moderna’s TeenCove study of adolescents ages 12-17 years began slowly in late December, but the pace has since picked up, said company spokesperson Colleen Hussey. “We continue to bring clinical trial sites online, and we are on track to provide updated data around mid-year 2021.” A trial extension in children 11 years and younger is expected to begin later in 2021.

Johnson & Johnson and AstraZeneca said they expect to begin adolescent trials in early 2021, according to data shared by the Advisory Committee on Immunization Practices. An interim analysis of J&J’s Janssen COVID-19 vaccine trial data, released on Jan. 29, showed it was 72% effective in US participants aged 18 years or older. AstraZeneca’s U.S. trial in adults is ongoing.
 

Easing the burden

Vaccination could lessen children’s risk of severe disease as well as the social and emotional burdens of the pandemic, says James Campbell, MD, a pediatric infectious disease specialist at the University of Maryland’s Center for Vaccine Development in Baltimore, which was involved in the Moderna and early-phase Pfizer trials. He coauthored a September 2020 article in Clinical Infectious Diseases titled: “Warp Speed for COVID-19 vaccines: Why are children stuck in neutral?”

The adolescent trials are a vital step to ensure timely vaccine access for teens and younger children. “It is reasonable, when you have limited vaccine, that your rollout goes to the highest priority and then moves to lower and lower priorities. In adults, we’re just saying: ‘Wait your turn,’ ” he said of the current vaccination effort. “If we didn’t have the [vaccine trial] data in children, we’d be saying: ‘You don’t have a turn.’ ”

As the pandemic has worn on, the burden on children has grown. As of Tuesday, 269 children had died of COVID-19. That is well above the highest annual death toll recorded during a regular flu season – 188 flu deaths among children and adolescents under 18 in the 2019-2020 and 2017-2018 flu seasons.

Children are less likely to transmit COVID-19 in their household than adults, according to a meta-analysis of 54 studies published in JAMA Network Open. But that does not necessarily mean children are less infectious, the authors said, noting that unmeasured factors could have affected the spread of infection among adults.

Moreover, children and adolescents need protection from COVID infection – and from the potential for severe disease or lingering effects – and, given that there are 74 million children and teens in the United States, their vaccination is an important part of stopping the pandemic, said Grace Lee, MD, professor of pediatrics at Stanford (Calif.) University, and cochair of ACIP’s COVID-19 Vaccine Safety Technical Subgroup.

“In order to interrupt transmission, I don’t see how we’re going to do that without vaccinating children and adolescents,” she said.

Dr. Lee said her 16-year-old daughter misses the normal teenage social life and is excited about getting the vaccine when she is eligible. (Adolescents without high-risk conditions are in the lowest vaccination tier, according to ACIP recommendations.) “There is truly individual protection to be gained,” Dr. Lee said.

She noted that researchers continue to assess the immune responses to the adult vaccines – even looking at immune characteristics of the small percentage of people who aren’t protected from infection – and that information helps in the evaluation of the pediatric immune responses. As the trials expand to younger children and infants, dosing will be a major focus. “How many doses do they need they need to receive the same immunity? Safety considerations will be critically important,” she said.
 

Teen trials underway

Pfizer/BioNTech extended its adult trial to 16- and 17-year-olds in October, which enabled older teens to be included in its emergency-use authorization. They and younger teens, ages 12-15, receive the same dose as adults.

The ongoing trials with Pfizer and Moderna vaccines are immunobridging trials, designed to study safety and immunogenicity. Investigators will compare the teens’ immune response with the findings from the larger adult trials. When the trials expand to school-age children (6-12 years), protocols call for testing the safety and immunogenicity of a half-dose vaccine as well as the full dose.

Children ages 2-5 years and infants and toddlers will be enrolled in future trials, studying safety and immunogenicity of full, half, or even quarter dosages. The Pediatric Research Equity Act of 2003 requires licensed vaccines to be tested for safety and efficacy in children, unless they are not appropriate for a pediatric population.

Demand for the teen trials has been strong. At Cincinnati Children’s Hospital Medical Center, 259 teenagers joined the Pfizer/BioNTech trial, but some teenagers were turned away when the trial’s national enrollment closed in late January.

“Many of the children are having no side effects, and if they are, they’re having the same [effects] as the young adults – local redness or pain, fatigue, and headaches,” said Robert Frenck, MD, director of the Cincinnati Children’s Gamble Program for Clinical Studies.

Parents may share some of the vaccine hesitancy that has affected adult vaccination. But that is balanced by the hope that vaccines will end the pandemic and usher in a new normal. “If it looks like [vaccines] will increase the likelihood of children returning to school safely, that may be a motivating factor,” Dr. Frenck said.

Cody Meissner, MD, chief of the pediatric infectious disease service at Tufts Medical Center, Boston, was initially cautious about the extension of vaccination to adolescents. A member of the Vaccine and Related Biological Products Advisory Committee, which evaluates data and makes recommendations to the Food and Drug Administration, Dr. Meissner initially abstained in the vote on the Pfizer/BioNTech emergency-use authorization for people 16 and older.

He noted that, at the time the committee reviewed the Pfizer vaccine, the company had data available for just 134 teenagers, half of whom received a placebo. But the vaccination of 34 million adults has provided robust data about the vaccine’s safety, and the trial expansion into adolescents is important.

“I’m comfortable with the way these trials are going now,” he said. “This is the way I was hoping they would go.”

Ms. Hillenburg is on the parent advisory board of Voices for Vaccines, an organization of parents supporting vaccination that is affiliated with the Task Force for Global Health, an Atlanta-based independent public health organization. Dr. Campbell’s institution has received funds to conduct clinical trials from the National Institutes of Health and several companies, including Merck, GlaxoSmithKline, Sanofi, Pfizer, and Moderna. He has served pro bono on many safety and data monitoring committees. Dr. Frenck’s institution is receiving funds to conduct the Pfizer trial. In the past 5 years, he has also participated in clinical trials for GlaxoSmithKline, Merck, and Meissa vaccines. Dr. Lee and Dr. Meissner disclosed no relevant financial relationships.

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

While 34 million adults in the United States have received a COVID-19 vaccine, children and teenagers are waiting at the back of the line, mostly ineligible for the authorized vaccines. That secondary status is rapidly changing though, as experts expect vaccinations of adolescents to begin by this summer.

The vaccinations can’t come soon enough for parents like Stacy Hillenburg, a developmental therapist in Aurora, Ill., whose 9-year-old son takes immunosuppressants because he had a heart transplant when he was 7 weeks old. Although school-age children aren’t yet included in clinical trials, if her 12- and 13-year-old daughters could get vaccinated, along with both parents, then the family could relax some of the protocols they currently follow to prevent infection.

Whenever they are around other people, even masked and socially distanced, they come home and immediately shower and change their clothes. So far, no one in the family has been infected with COVID, but the anxiety is ever-present. “I can’t wait for it to come out,” Ms. Hillenburg said of a pediatric COVID vaccine. “It will ease my mind so much.”

She isn’t alone in that anticipation. In the fall, the American Academy of Pediatrics and other pediatric vaccine experts urged faster action on pediatric vaccine trials and worried that children would be left behind as adults gained protection from COVID. But recent developments have eased those concerns.

“Over the next couple of months, we will be doing trials in an age-deescalation manner,” with studies moving gradually to younger children, Anthony S. Fauci, MD, chief medical adviser on COVID-19 to the president, said in a coronavirus response team briefing on Jan. 29. “So that hopefully, as we get to the late spring and summer, we will have children being able to be vaccinated.”

Pfizer completed enrollment of 2,259 teens aged 12-15 years in late January and expects to move forward with a separate pediatric trial of children aged 5-11 years by this spring, Keanna Ghazvini, senior associate for global media relations at Pfizer, said in an interview.

Enrollment in Moderna’s TeenCove study of adolescents ages 12-17 years began slowly in late December, but the pace has since picked up, said company spokesperson Colleen Hussey. “We continue to bring clinical trial sites online, and we are on track to provide updated data around mid-year 2021.” A trial extension in children 11 years and younger is expected to begin later in 2021.

Johnson & Johnson and AstraZeneca said they expect to begin adolescent trials in early 2021, according to data shared by the Advisory Committee on Immunization Practices. An interim analysis of J&J’s Janssen COVID-19 vaccine trial data, released on Jan. 29, showed it was 72% effective in US participants aged 18 years or older. AstraZeneca’s U.S. trial in adults is ongoing.
 

Easing the burden

Vaccination could lessen children’s risk of severe disease as well as the social and emotional burdens of the pandemic, says James Campbell, MD, a pediatric infectious disease specialist at the University of Maryland’s Center for Vaccine Development in Baltimore, which was involved in the Moderna and early-phase Pfizer trials. He coauthored a September 2020 article in Clinical Infectious Diseases titled: “Warp Speed for COVID-19 vaccines: Why are children stuck in neutral?”

The adolescent trials are a vital step to ensure timely vaccine access for teens and younger children. “It is reasonable, when you have limited vaccine, that your rollout goes to the highest priority and then moves to lower and lower priorities. In adults, we’re just saying: ‘Wait your turn,’ ” he said of the current vaccination effort. “If we didn’t have the [vaccine trial] data in children, we’d be saying: ‘You don’t have a turn.’ ”

As the pandemic has worn on, the burden on children has grown. As of Tuesday, 269 children had died of COVID-19. That is well above the highest annual death toll recorded during a regular flu season – 188 flu deaths among children and adolescents under 18 in the 2019-2020 and 2017-2018 flu seasons.

Children are less likely to transmit COVID-19 in their household than adults, according to a meta-analysis of 54 studies published in JAMA Network Open. But that does not necessarily mean children are less infectious, the authors said, noting that unmeasured factors could have affected the spread of infection among adults.

Moreover, children and adolescents need protection from COVID infection – and from the potential for severe disease or lingering effects – and, given that there are 74 million children and teens in the United States, their vaccination is an important part of stopping the pandemic, said Grace Lee, MD, professor of pediatrics at Stanford (Calif.) University, and cochair of ACIP’s COVID-19 Vaccine Safety Technical Subgroup.

“In order to interrupt transmission, I don’t see how we’re going to do that without vaccinating children and adolescents,” she said.

Dr. Lee said her 16-year-old daughter misses the normal teenage social life and is excited about getting the vaccine when she is eligible. (Adolescents without high-risk conditions are in the lowest vaccination tier, according to ACIP recommendations.) “There is truly individual protection to be gained,” Dr. Lee said.

She noted that researchers continue to assess the immune responses to the adult vaccines – even looking at immune characteristics of the small percentage of people who aren’t protected from infection – and that information helps in the evaluation of the pediatric immune responses. As the trials expand to younger children and infants, dosing will be a major focus. “How many doses do they need they need to receive the same immunity? Safety considerations will be critically important,” she said.
 

Teen trials underway

Pfizer/BioNTech extended its adult trial to 16- and 17-year-olds in October, which enabled older teens to be included in its emergency-use authorization. They and younger teens, ages 12-15, receive the same dose as adults.

The ongoing trials with Pfizer and Moderna vaccines are immunobridging trials, designed to study safety and immunogenicity. Investigators will compare the teens’ immune response with the findings from the larger adult trials. When the trials expand to school-age children (6-12 years), protocols call for testing the safety and immunogenicity of a half-dose vaccine as well as the full dose.

Children ages 2-5 years and infants and toddlers will be enrolled in future trials, studying safety and immunogenicity of full, half, or even quarter dosages. The Pediatric Research Equity Act of 2003 requires licensed vaccines to be tested for safety and efficacy in children, unless they are not appropriate for a pediatric population.

Demand for the teen trials has been strong. At Cincinnati Children’s Hospital Medical Center, 259 teenagers joined the Pfizer/BioNTech trial, but some teenagers were turned away when the trial’s national enrollment closed in late January.

“Many of the children are having no side effects, and if they are, they’re having the same [effects] as the young adults – local redness or pain, fatigue, and headaches,” said Robert Frenck, MD, director of the Cincinnati Children’s Gamble Program for Clinical Studies.

Parents may share some of the vaccine hesitancy that has affected adult vaccination. But that is balanced by the hope that vaccines will end the pandemic and usher in a new normal. “If it looks like [vaccines] will increase the likelihood of children returning to school safely, that may be a motivating factor,” Dr. Frenck said.

Cody Meissner, MD, chief of the pediatric infectious disease service at Tufts Medical Center, Boston, was initially cautious about the extension of vaccination to adolescents. A member of the Vaccine and Related Biological Products Advisory Committee, which evaluates data and makes recommendations to the Food and Drug Administration, Dr. Meissner initially abstained in the vote on the Pfizer/BioNTech emergency-use authorization for people 16 and older.

He noted that, at the time the committee reviewed the Pfizer vaccine, the company had data available for just 134 teenagers, half of whom received a placebo. But the vaccination of 34 million adults has provided robust data about the vaccine’s safety, and the trial expansion into adolescents is important.

“I’m comfortable with the way these trials are going now,” he said. “This is the way I was hoping they would go.”

Ms. Hillenburg is on the parent advisory board of Voices for Vaccines, an organization of parents supporting vaccination that is affiliated with the Task Force for Global Health, an Atlanta-based independent public health organization. Dr. Campbell’s institution has received funds to conduct clinical trials from the National Institutes of Health and several companies, including Merck, GlaxoSmithKline, Sanofi, Pfizer, and Moderna. He has served pro bono on many safety and data monitoring committees. Dr. Frenck’s institution is receiving funds to conduct the Pfizer trial. In the past 5 years, he has also participated in clinical trials for GlaxoSmithKline, Merck, and Meissa vaccines. Dr. Lee and Dr. Meissner disclosed no relevant financial relationships.

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

While 34 million adults in the United States have received a COVID-19 vaccine, children and teenagers are waiting at the back of the line, mostly ineligible for the authorized vaccines. That secondary status is rapidly changing though, as experts expect vaccinations of adolescents to begin by this summer.

The vaccinations can’t come soon enough for parents like Stacy Hillenburg, a developmental therapist in Aurora, Ill., whose 9-year-old son takes immunosuppressants because he had a heart transplant when he was 7 weeks old. Although school-age children aren’t yet included in clinical trials, if her 12- and 13-year-old daughters could get vaccinated, along with both parents, then the family could relax some of the protocols they currently follow to prevent infection.

Whenever they are around other people, even masked and socially distanced, they come home and immediately shower and change their clothes. So far, no one in the family has been infected with COVID, but the anxiety is ever-present. “I can’t wait for it to come out,” Ms. Hillenburg said of a pediatric COVID vaccine. “It will ease my mind so much.”

She isn’t alone in that anticipation. In the fall, the American Academy of Pediatrics and other pediatric vaccine experts urged faster action on pediatric vaccine trials and worried that children would be left behind as adults gained protection from COVID. But recent developments have eased those concerns.

“Over the next couple of months, we will be doing trials in an age-deescalation manner,” with studies moving gradually to younger children, Anthony S. Fauci, MD, chief medical adviser on COVID-19 to the president, said in a coronavirus response team briefing on Jan. 29. “So that hopefully, as we get to the late spring and summer, we will have children being able to be vaccinated.”

Pfizer completed enrollment of 2,259 teens aged 12-15 years in late January and expects to move forward with a separate pediatric trial of children aged 5-11 years by this spring, Keanna Ghazvini, senior associate for global media relations at Pfizer, said in an interview.

Enrollment in Moderna’s TeenCove study of adolescents ages 12-17 years began slowly in late December, but the pace has since picked up, said company spokesperson Colleen Hussey. “We continue to bring clinical trial sites online, and we are on track to provide updated data around mid-year 2021.” A trial extension in children 11 years and younger is expected to begin later in 2021.

Johnson & Johnson and AstraZeneca said they expect to begin adolescent trials in early 2021, according to data shared by the Advisory Committee on Immunization Practices. An interim analysis of J&J’s Janssen COVID-19 vaccine trial data, released on Jan. 29, showed it was 72% effective in US participants aged 18 years or older. AstraZeneca’s U.S. trial in adults is ongoing.
 

Easing the burden

Vaccination could lessen children’s risk of severe disease as well as the social and emotional burdens of the pandemic, says James Campbell, MD, a pediatric infectious disease specialist at the University of Maryland’s Center for Vaccine Development in Baltimore, which was involved in the Moderna and early-phase Pfizer trials. He coauthored a September 2020 article in Clinical Infectious Diseases titled: “Warp Speed for COVID-19 vaccines: Why are children stuck in neutral?”

The adolescent trials are a vital step to ensure timely vaccine access for teens and younger children. “It is reasonable, when you have limited vaccine, that your rollout goes to the highest priority and then moves to lower and lower priorities. In adults, we’re just saying: ‘Wait your turn,’ ” he said of the current vaccination effort. “If we didn’t have the [vaccine trial] data in children, we’d be saying: ‘You don’t have a turn.’ ”

As the pandemic has worn on, the burden on children has grown. As of Tuesday, 269 children had died of COVID-19. That is well above the highest annual death toll recorded during a regular flu season – 188 flu deaths among children and adolescents under 18 in the 2019-2020 and 2017-2018 flu seasons.

Children are less likely to transmit COVID-19 in their household than adults, according to a meta-analysis of 54 studies published in JAMA Network Open. But that does not necessarily mean children are less infectious, the authors said, noting that unmeasured factors could have affected the spread of infection among adults.

Moreover, children and adolescents need protection from COVID infection – and from the potential for severe disease or lingering effects – and, given that there are 74 million children and teens in the United States, their vaccination is an important part of stopping the pandemic, said Grace Lee, MD, professor of pediatrics at Stanford (Calif.) University, and cochair of ACIP’s COVID-19 Vaccine Safety Technical Subgroup.

“In order to interrupt transmission, I don’t see how we’re going to do that without vaccinating children and adolescents,” she said.

Dr. Lee said her 16-year-old daughter misses the normal teenage social life and is excited about getting the vaccine when she is eligible. (Adolescents without high-risk conditions are in the lowest vaccination tier, according to ACIP recommendations.) “There is truly individual protection to be gained,” Dr. Lee said.

She noted that researchers continue to assess the immune responses to the adult vaccines – even looking at immune characteristics of the small percentage of people who aren’t protected from infection – and that information helps in the evaluation of the pediatric immune responses. As the trials expand to younger children and infants, dosing will be a major focus. “How many doses do they need they need to receive the same immunity? Safety considerations will be critically important,” she said.
 

Teen trials underway

Pfizer/BioNTech extended its adult trial to 16- and 17-year-olds in October, which enabled older teens to be included in its emergency-use authorization. They and younger teens, ages 12-15, receive the same dose as adults.

The ongoing trials with Pfizer and Moderna vaccines are immunobridging trials, designed to study safety and immunogenicity. Investigators will compare the teens’ immune response with the findings from the larger adult trials. When the trials expand to school-age children (6-12 years), protocols call for testing the safety and immunogenicity of a half-dose vaccine as well as the full dose.

Children ages 2-5 years and infants and toddlers will be enrolled in future trials, studying safety and immunogenicity of full, half, or even quarter dosages. The Pediatric Research Equity Act of 2003 requires licensed vaccines to be tested for safety and efficacy in children, unless they are not appropriate for a pediatric population.

Demand for the teen trials has been strong. At Cincinnati Children’s Hospital Medical Center, 259 teenagers joined the Pfizer/BioNTech trial, but some teenagers were turned away when the trial’s national enrollment closed in late January.

“Many of the children are having no side effects, and if they are, they’re having the same [effects] as the young adults – local redness or pain, fatigue, and headaches,” said Robert Frenck, MD, director of the Cincinnati Children’s Gamble Program for Clinical Studies.

Parents may share some of the vaccine hesitancy that has affected adult vaccination. But that is balanced by the hope that vaccines will end the pandemic and usher in a new normal. “If it looks like [vaccines] will increase the likelihood of children returning to school safely, that may be a motivating factor,” Dr. Frenck said.

Cody Meissner, MD, chief of the pediatric infectious disease service at Tufts Medical Center, Boston, was initially cautious about the extension of vaccination to adolescents. A member of the Vaccine and Related Biological Products Advisory Committee, which evaluates data and makes recommendations to the Food and Drug Administration, Dr. Meissner initially abstained in the vote on the Pfizer/BioNTech emergency-use authorization for people 16 and older.

He noted that, at the time the committee reviewed the Pfizer vaccine, the company had data available for just 134 teenagers, half of whom received a placebo. But the vaccination of 34 million adults has provided robust data about the vaccine’s safety, and the trial expansion into adolescents is important.

“I’m comfortable with the way these trials are going now,” he said. “This is the way I was hoping they would go.”

Ms. Hillenburg is on the parent advisory board of Voices for Vaccines, an organization of parents supporting vaccination that is affiliated with the Task Force for Global Health, an Atlanta-based independent public health organization. Dr. Campbell’s institution has received funds to conduct clinical trials from the National Institutes of Health and several companies, including Merck, GlaxoSmithKline, Sanofi, Pfizer, and Moderna. He has served pro bono on many safety and data monitoring committees. Dr. Frenck’s institution is receiving funds to conduct the Pfizer trial. In the past 5 years, he has also participated in clinical trials for GlaxoSmithKline, Merck, and Meissa vaccines. Dr. Lee and Dr. Meissner disclosed no relevant financial relationships.

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

Honeybees, Apis mellifera, play an important role in the web of life. We rely on bees for pollinating approximately one-third of our crops, including multiple fruits, vegetables, nuts, and seeds.^1,2 Bees are also instrumental in the propagation of other plants, flower nectar, and flower pollen. A. mellifera, the European honeybee, is the main pollinator in Europe and North America, but other species, including A. cerana, A. dorsata, A. floria, A. andreniformis, A. koschevnikov, and A. laboriosa, yield honey.³ Honey, propolis, and royal jelly, along with beeswax and bee pollen, are among some of the celebrated bee products that have been found to confer health benefits to human beings.^4,5 Bee venom, a toxin bees use for protection, is a convoluted combination of peptides and toxic proteins such as phospholipase A2 (PLA2) and melittin that has garnered significant scientific attention of late and is used to treat various inflammatory conditions.^6-8 This column will focus on the investigation of the use of bee venom to treat atopic dermatitis (AD) and acne.

temmuzcan/Getty Images

Atopic dermatitis

In 2013, Kim et al. assessed the impact of bee venom on AD-related symptoms in mice, finding that it attenuated the effects of AD-simulating compounds in 48 of 80 patients injected subcutaneously. They concluded that bee venom acted by suppressing mast cell degranulation and proinflammatory cytokine expression.⁹ Three years later, You et al. conducted a double-blind, randomized, base-controlled multicenter study of 136 patients with AD to ascertain the effects of a bee venom emollient. For 4 weeks, patients applied an emollient with bee venom and silk protein or a vehicle lacking bee venom twice daily. Eczema area and severity index (EASI) scores were significantly lower in the bee venom group, as were the visual analogue scale (VAS) scores. The investigators concluded that bee venom is an effective and safe therapeutic choice for treating patients with AD.¹⁰ Further, in 2018, Shin et al. demonstrated that PLA2 derived from bee venom mitigates atopic skin inflammation via the CD206 mannose receptor. They had previously shown in a mouse model that PLA2 from bee venom exerts such activity against AD-like lesions induced by 2,4-dinitrochlorobenzene (DNCB) and house dust mite (Dermatophagoides farinae) extract.¹¹ Gu et al. observed later that year that intraperitoneal administration of bee venom eased the symptoms of ovalbumin-induced AD-like skin lesions in an experimental mouse model. Bee venom also lowered serum immunoglobulin E levels and suppressed infiltration of eosinophils and mast cells. They concluded that bee venom is a viable alternative for attenuating the allergic skin inflammation characteristic of AD.¹² At the end of 2018, An et al. reported on the use of an in vivo female Balb/c mouse AD model in which 1-chloro-DNCB acted as inducer in cultures of human keratinocytes, stimulated by TNF-alpha/IFN-gamma. The investigators found that bee venom and melittin displayed robust antiatopic effects as evidenced by reduced lesions. The bee products were also found to have hindered elevated expression of various chemokines and proinflammatory cytokines. The authors suggested that bee venom and melittin appear to warrant consideration as a topical treatment for AD.¹³ In 2019, Kim et al. demonstrated in mice that bee venom eases the symptoms of AD by inactivating the complement system, particularly through CD55 induction, which might account for its effectiveness in AD treatment in humans, they suggested.⁶ Early in 2020, Lee et al. demonstrated in a Balb/c mouse model that bee venom appears to be a possible therapeutic macromolecule for treating phthalic anhydride-induced AD.⁷
 

Acne

In 2013, in vitro experiments by Han et al. showed that purified bee venom exhibited antimicrobial activity, in a concentration-dependent manner, against Cutibacterium acnes (or Propionibacterium acnes). They followed up with a small randomized, double-blind, controlled trial with 12 subjects who were treated with cosmetics with pure bee venom or cosmetics without it for two weeks. The group receiving bee venom experienced significantly fewer inflammatory and noninflammatory lesions, and a significant decline in adenosine triphosphate levels (a 57.5% reduction) was noted in subjects in the bee venom group, with a nonsignificant decrease of 4.7% observed in the control group. The investigators concluded the purified bee venom may be suitable as an antiacne agent.¹⁴ Using a mouse model, An et al. studied the therapeutic effects of bee venom against C. acnes–induced skin inflammation. They found that bee venom significantly diminished the volume of infiltrated inflammatory cells in the treated mice, compared with untreated mice. Bee venom also decreased expression levels of tumor necrosis factor (TNF)-α, and interleukin (IL)-1beta and suppressed Toll-like receptor (TLR)2 and CD14 expression in C. acnes–injected tissue. The investigators concluded that bee venom imparts notable anti-inflammatory activity and has potential for use in treating acne and as an anti-inflammatory agent in skin care.¹⁵

In 2015, Kim et al. studied the influence of bee venom against C. acnes–induced inflammation in human keratinocytes (HaCaT) and monocytes (THP-1). They found that bee venom successfully suppressed the secretion of interferon-gamma, IL-1beta, IL-8, and TNF-alpha. It also galvanized the expression of IL-8 and TLR2 in HaCaT cells but hampered their expression in heat-killed C. acnes. The researchers concluded that bee venom displays considerable anti-inflammatory activity against C. acnes and warrants consideration as an alternative to antibiotic acne treatment.¹⁶ It is worth noting that early that year, in a comprehensive database review to evaluate the effects and safety of a wide range of complementary treatments for acne, Cao et al. found, among 35 studies including parallel-group randomized controlled trials, that one trial indicated bee venom was superior to control in lowering the number of acne lesions.¹⁷
 

Conclusion

More research, in the form of randomized, controlled trials, is required before bee venom can be incorporated into the dermatologic armamentarium as a first-line therapy for common and vexing cutaneous conditions. Nevertheless, the current evidence provides reasons for optimism that bee venom can play a role among the various treatments for AD and acne.
 

Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur who practices in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann has written two textbooks and a New York Times Best Sellers book for consumers. Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Galderma, Revance, Evolus, and Burt’s Bees. She is the CEO of Skin Type Solutions Inc., a company that independently tests skin care products and makes recommendations to physicians on which skin care technologies are best. Write to her at [email protected].

References

1. Walsh B. The plight of the honeybee: Mass deaths in bee colonies may mean disaster for farmers – and your favorite Foods. Time Magazine, 2013 Aug 19.

2. Klein AM et al. Proc Biol Sci. 2007 Feb 7;274(1608):303-13. doi: 10.1098/rspb.2006.3721.

3. Ediriweera ER and Premarathna NY. AYU. 2012 Apr;33(2):178-82. doi: 10.4103/0974-8520.105233.

4. Baumann, L. Honey/Propolis/Royal Jelly. In Cosmeceuticals and Cosmetic Ingredients. New York:McGraw-Hill; 2014:203-212.

5. Cornara L et al. Front Pharmacol. 2017 Jun 28;8:412. doi: 10.3389/fphar.2017.00412.

6. Kim Y et al. Toxins (Basel). 2019 Apr 26;11(5):239. doi: 10.3390/toxins11050239.

7. Lee YJ et al. Inflammopharmacology. 2020 Feb;28(1):253-63. doi: 10.1007/s10787-019-00646-w.

8. Lee G and Bae H. Molecules. 2016 May 11;21(5):616. doi: 10.3390/molecules21050616.

9. Kim KH et al. Int J Clin Exp Pathol. 2013 Nov 15;6(12):2896-903.

10. You CE et al. Ann Dermatol. 2016 Oct;28(5):593-9. doi: 10.5021/ad.2016.28.5.593.

11. Shin D et al. Toxins (Basel). 2018 Apr 2;10(4):146. doi: 10.3390/toxins10040146.

12. Gu H et al. Mol Med Rep. 2018 Oct;18(4):3711-8. doi: 10.3892/mmr.2018.9398.

13. An HJ et al. Br J Pharmacol. 2018 Dec;175(23):4310-24. doi: 10.1111/bph.14487.

14. Han SM et al. J Integr Med. 2013 Sep;11(5):320-6. doi: 10.3736/jintegrmed2013043.

15. An HJ et al. Int J Mol Med. 2014 Nov;34(5):1341-8. doi: 10.3892/ijmm.2014.1933.

16. Kim JY et al. Int J Mol Med. 2015 Jun;35(6):1651-6. doi: 10.3892/ijmm.2015.2180.

17. Cao H et al. Cochrane Database Syst Rev. 2015 Jan 19;1:CD009436. doi: 10.1002/14651858.CD009436.pub2.

Honeybees, Apis mellifera, play an important role in the web of life. We rely on bees for pollinating approximately one-third of our crops, including multiple fruits, vegetables, nuts, and seeds.^1,2 Bees are also instrumental in the propagation of other plants, flower nectar, and flower pollen. A. mellifera, the European honeybee, is the main pollinator in Europe and North America, but other species, including A. cerana, A. dorsata, A. floria, A. andreniformis, A. koschevnikov, and A. laboriosa, yield honey.³ Honey, propolis, and royal jelly, along with beeswax and bee pollen, are among some of the celebrated bee products that have been found to confer health benefits to human beings.^4,5 Bee venom, a toxin bees use for protection, is a convoluted combination of peptides and toxic proteins such as phospholipase A2 (PLA2) and melittin that has garnered significant scientific attention of late and is used to treat various inflammatory conditions.^6-8 This column will focus on the investigation of the use of bee venom to treat atopic dermatitis (AD) and acne.

temmuzcan/Getty Images

Atopic dermatitis

In 2013, Kim et al. assessed the impact of bee venom on AD-related symptoms in mice, finding that it attenuated the effects of AD-simulating compounds in 48 of 80 patients injected subcutaneously. They concluded that bee venom acted by suppressing mast cell degranulation and proinflammatory cytokine expression.⁹ Three years later, You et al. conducted a double-blind, randomized, base-controlled multicenter study of 136 patients with AD to ascertain the effects of a bee venom emollient. For 4 weeks, patients applied an emollient with bee venom and silk protein or a vehicle lacking bee venom twice daily. Eczema area and severity index (EASI) scores were significantly lower in the bee venom group, as were the visual analogue scale (VAS) scores. The investigators concluded that bee venom is an effective and safe therapeutic choice for treating patients with AD.¹⁰ Further, in 2018, Shin et al. demonstrated that PLA2 derived from bee venom mitigates atopic skin inflammation via the CD206 mannose receptor. They had previously shown in a mouse model that PLA2 from bee venom exerts such activity against AD-like lesions induced by 2,4-dinitrochlorobenzene (DNCB) and house dust mite (Dermatophagoides farinae) extract.¹¹ Gu et al. observed later that year that intraperitoneal administration of bee venom eased the symptoms of ovalbumin-induced AD-like skin lesions in an experimental mouse model. Bee venom also lowered serum immunoglobulin E levels and suppressed infiltration of eosinophils and mast cells. They concluded that bee venom is a viable alternative for attenuating the allergic skin inflammation characteristic of AD.¹² At the end of 2018, An et al. reported on the use of an in vivo female Balb/c mouse AD model in which 1-chloro-DNCB acted as inducer in cultures of human keratinocytes, stimulated by TNF-alpha/IFN-gamma. The investigators found that bee venom and melittin displayed robust antiatopic effects as evidenced by reduced lesions. The bee products were also found to have hindered elevated expression of various chemokines and proinflammatory cytokines. The authors suggested that bee venom and melittin appear to warrant consideration as a topical treatment for AD.¹³ In 2019, Kim et al. demonstrated in mice that bee venom eases the symptoms of AD by inactivating the complement system, particularly through CD55 induction, which might account for its effectiveness in AD treatment in humans, they suggested.⁶ Early in 2020, Lee et al. demonstrated in a Balb/c mouse model that bee venom appears to be a possible therapeutic macromolecule for treating phthalic anhydride-induced AD.⁷
 

Acne

In 2013, in vitro experiments by Han et al. showed that purified bee venom exhibited antimicrobial activity, in a concentration-dependent manner, against Cutibacterium acnes (or Propionibacterium acnes). They followed up with a small randomized, double-blind, controlled trial with 12 subjects who were treated with cosmetics with pure bee venom or cosmetics without it for two weeks. The group receiving bee venom experienced significantly fewer inflammatory and noninflammatory lesions, and a significant decline in adenosine triphosphate levels (a 57.5% reduction) was noted in subjects in the bee venom group, with a nonsignificant decrease of 4.7% observed in the control group. The investigators concluded the purified bee venom may be suitable as an antiacne agent.¹⁴ Using a mouse model, An et al. studied the therapeutic effects of bee venom against C. acnes–induced skin inflammation. They found that bee venom significantly diminished the volume of infiltrated inflammatory cells in the treated mice, compared with untreated mice. Bee venom also decreased expression levels of tumor necrosis factor (TNF)-α, and interleukin (IL)-1beta and suppressed Toll-like receptor (TLR)2 and CD14 expression in C. acnes–injected tissue. The investigators concluded that bee venom imparts notable anti-inflammatory activity and has potential for use in treating acne and as an anti-inflammatory agent in skin care.¹⁵

In 2015, Kim et al. studied the influence of bee venom against C. acnes–induced inflammation in human keratinocytes (HaCaT) and monocytes (THP-1). They found that bee venom successfully suppressed the secretion of interferon-gamma, IL-1beta, IL-8, and TNF-alpha. It also galvanized the expression of IL-8 and TLR2 in HaCaT cells but hampered their expression in heat-killed C. acnes. The researchers concluded that bee venom displays considerable anti-inflammatory activity against C. acnes and warrants consideration as an alternative to antibiotic acne treatment.¹⁶ It is worth noting that early that year, in a comprehensive database review to evaluate the effects and safety of a wide range of complementary treatments for acne, Cao et al. found, among 35 studies including parallel-group randomized controlled trials, that one trial indicated bee venom was superior to control in lowering the number of acne lesions.¹⁷
 

Conclusion

More research, in the form of randomized, controlled trials, is required before bee venom can be incorporated into the dermatologic armamentarium as a first-line therapy for common and vexing cutaneous conditions. Nevertheless, the current evidence provides reasons for optimism that bee venom can play a role among the various treatments for AD and acne.
 

Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur who practices in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann has written two textbooks and a New York Times Best Sellers book for consumers. Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Galderma, Revance, Evolus, and Burt’s Bees. She is the CEO of Skin Type Solutions Inc., a company that independently tests skin care products and makes recommendations to physicians on which skin care technologies are best. Write to her at [email protected].

References

1. Walsh B. The plight of the honeybee: Mass deaths in bee colonies may mean disaster for farmers – and your favorite Foods. Time Magazine, 2013 Aug 19.

2. Klein AM et al. Proc Biol Sci. 2007 Feb 7;274(1608):303-13. doi: 10.1098/rspb.2006.3721.

3. Ediriweera ER and Premarathna NY. AYU. 2012 Apr;33(2):178-82. doi: 10.4103/0974-8520.105233.

4. Baumann, L. Honey/Propolis/Royal Jelly. In Cosmeceuticals and Cosmetic Ingredients. New York:McGraw-Hill; 2014:203-212.

5. Cornara L et al. Front Pharmacol. 2017 Jun 28;8:412. doi: 10.3389/fphar.2017.00412.

6. Kim Y et al. Toxins (Basel). 2019 Apr 26;11(5):239. doi: 10.3390/toxins11050239.

7. Lee YJ et al. Inflammopharmacology. 2020 Feb;28(1):253-63. doi: 10.1007/s10787-019-00646-w.

8. Lee G and Bae H. Molecules. 2016 May 11;21(5):616. doi: 10.3390/molecules21050616.

9. Kim KH et al. Int J Clin Exp Pathol. 2013 Nov 15;6(12):2896-903.

10. You CE et al. Ann Dermatol. 2016 Oct;28(5):593-9. doi: 10.5021/ad.2016.28.5.593.

11. Shin D et al. Toxins (Basel). 2018 Apr 2;10(4):146. doi: 10.3390/toxins10040146.

12. Gu H et al. Mol Med Rep. 2018 Oct;18(4):3711-8. doi: 10.3892/mmr.2018.9398.

13. An HJ et al. Br J Pharmacol. 2018 Dec;175(23):4310-24. doi: 10.1111/bph.14487.

14. Han SM et al. J Integr Med. 2013 Sep;11(5):320-6. doi: 10.3736/jintegrmed2013043.

15. An HJ et al. Int J Mol Med. 2014 Nov;34(5):1341-8. doi: 10.3892/ijmm.2014.1933.

16. Kim JY et al. Int J Mol Med. 2015 Jun;35(6):1651-6. doi: 10.3892/ijmm.2015.2180.

17. Cao H et al. Cochrane Database Syst Rev. 2015 Jan 19;1:CD009436. doi: 10.1002/14651858.CD009436.pub2.

Honeybees, Apis mellifera, play an important role in the web of life. We rely on bees for pollinating approximately one-third of our crops, including multiple fruits, vegetables, nuts, and seeds.^1,2 Bees are also instrumental in the propagation of other plants, flower nectar, and flower pollen. A. mellifera, the European honeybee, is the main pollinator in Europe and North America, but other species, including A. cerana, A. dorsata, A. floria, A. andreniformis, A. koschevnikov, and A. laboriosa, yield honey.³ Honey, propolis, and royal jelly, along with beeswax and bee pollen, are among some of the celebrated bee products that have been found to confer health benefits to human beings.^4,5 Bee venom, a toxin bees use for protection, is a convoluted combination of peptides and toxic proteins such as phospholipase A2 (PLA2) and melittin that has garnered significant scientific attention of late and is used to treat various inflammatory conditions.^6-8 This column will focus on the investigation of the use of bee venom to treat atopic dermatitis (AD) and acne.

temmuzcan/Getty Images

Atopic dermatitis

In 2013, Kim et al. assessed the impact of bee venom on AD-related symptoms in mice, finding that it attenuated the effects of AD-simulating compounds in 48 of 80 patients injected subcutaneously. They concluded that bee venom acted by suppressing mast cell degranulation and proinflammatory cytokine expression.⁹ Three years later, You et al. conducted a double-blind, randomized, base-controlled multicenter study of 136 patients with AD to ascertain the effects of a bee venom emollient. For 4 weeks, patients applied an emollient with bee venom and silk protein or a vehicle lacking bee venom twice daily. Eczema area and severity index (EASI) scores were significantly lower in the bee venom group, as were the visual analogue scale (VAS) scores. The investigators concluded that bee venom is an effective and safe therapeutic choice for treating patients with AD.¹⁰ Further, in 2018, Shin et al. demonstrated that PLA2 derived from bee venom mitigates atopic skin inflammation via the CD206 mannose receptor. They had previously shown in a mouse model that PLA2 from bee venom exerts such activity against AD-like lesions induced by 2,4-dinitrochlorobenzene (DNCB) and house dust mite (Dermatophagoides farinae) extract.¹¹ Gu et al. observed later that year that intraperitoneal administration of bee venom eased the symptoms of ovalbumin-induced AD-like skin lesions in an experimental mouse model. Bee venom also lowered serum immunoglobulin E levels and suppressed infiltration of eosinophils and mast cells. They concluded that bee venom is a viable alternative for attenuating the allergic skin inflammation characteristic of AD.¹² At the end of 2018, An et al. reported on the use of an in vivo female Balb/c mouse AD model in which 1-chloro-DNCB acted as inducer in cultures of human keratinocytes, stimulated by TNF-alpha/IFN-gamma. The investigators found that bee venom and melittin displayed robust antiatopic effects as evidenced by reduced lesions. The bee products were also found to have hindered elevated expression of various chemokines and proinflammatory cytokines. The authors suggested that bee venom and melittin appear to warrant consideration as a topical treatment for AD.¹³ In 2019, Kim et al. demonstrated in mice that bee venom eases the symptoms of AD by inactivating the complement system, particularly through CD55 induction, which might account for its effectiveness in AD treatment in humans, they suggested.⁶ Early in 2020, Lee et al. demonstrated in a Balb/c mouse model that bee venom appears to be a possible therapeutic macromolecule for treating phthalic anhydride-induced AD.⁷
 

Acne

In 2013, in vitro experiments by Han et al. showed that purified bee venom exhibited antimicrobial activity, in a concentration-dependent manner, against Cutibacterium acnes (or Propionibacterium acnes). They followed up with a small randomized, double-blind, controlled trial with 12 subjects who were treated with cosmetics with pure bee venom or cosmetics without it for two weeks. The group receiving bee venom experienced significantly fewer inflammatory and noninflammatory lesions, and a significant decline in adenosine triphosphate levels (a 57.5% reduction) was noted in subjects in the bee venom group, with a nonsignificant decrease of 4.7% observed in the control group. The investigators concluded the purified bee venom may be suitable as an antiacne agent.¹⁴ Using a mouse model, An et al. studied the therapeutic effects of bee venom against C. acnes–induced skin inflammation. They found that bee venom significantly diminished the volume of infiltrated inflammatory cells in the treated mice, compared with untreated mice. Bee venom also decreased expression levels of tumor necrosis factor (TNF)-α, and interleukin (IL)-1beta and suppressed Toll-like receptor (TLR)2 and CD14 expression in C. acnes–injected tissue. The investigators concluded that bee venom imparts notable anti-inflammatory activity and has potential for use in treating acne and as an anti-inflammatory agent in skin care.¹⁵

In 2015, Kim et al. studied the influence of bee venom against C. acnes–induced inflammation in human keratinocytes (HaCaT) and monocytes (THP-1). They found that bee venom successfully suppressed the secretion of interferon-gamma, IL-1beta, IL-8, and TNF-alpha. It also galvanized the expression of IL-8 and TLR2 in HaCaT cells but hampered their expression in heat-killed C. acnes. The researchers concluded that bee venom displays considerable anti-inflammatory activity against C. acnes and warrants consideration as an alternative to antibiotic acne treatment.¹⁶ It is worth noting that early that year, in a comprehensive database review to evaluate the effects and safety of a wide range of complementary treatments for acne, Cao et al. found, among 35 studies including parallel-group randomized controlled trials, that one trial indicated bee venom was superior to control in lowering the number of acne lesions.¹⁷
 

Conclusion

More research, in the form of randomized, controlled trials, is required before bee venom can be incorporated into the dermatologic armamentarium as a first-line therapy for common and vexing cutaneous conditions. Nevertheless, the current evidence provides reasons for optimism that bee venom can play a role among the various treatments for AD and acne.
 

Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur who practices in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann has written two textbooks and a New York Times Best Sellers book for consumers. Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Galderma, Revance, Evolus, and Burt’s Bees. She is the CEO of Skin Type Solutions Inc., a company that independently tests skin care products and makes recommendations to physicians on which skin care technologies are best. Write to her at [email protected].

References

1. Walsh B. The plight of the honeybee: Mass deaths in bee colonies may mean disaster for farmers – and your favorite Foods. Time Magazine, 2013 Aug 19.

2. Klein AM et al. Proc Biol Sci. 2007 Feb 7;274(1608):303-13. doi: 10.1098/rspb.2006.3721.

3. Ediriweera ER and Premarathna NY. AYU. 2012 Apr;33(2):178-82. doi: 10.4103/0974-8520.105233.

4. Baumann, L. Honey/Propolis/Royal Jelly. In Cosmeceuticals and Cosmetic Ingredients. New York:McGraw-Hill; 2014:203-212.

5. Cornara L et al. Front Pharmacol. 2017 Jun 28;8:412. doi: 10.3389/fphar.2017.00412.

6. Kim Y et al. Toxins (Basel). 2019 Apr 26;11(5):239. doi: 10.3390/toxins11050239.

7. Lee YJ et al. Inflammopharmacology. 2020 Feb;28(1):253-63. doi: 10.1007/s10787-019-00646-w.

8. Lee G and Bae H. Molecules. 2016 May 11;21(5):616. doi: 10.3390/molecules21050616.

9. Kim KH et al. Int J Clin Exp Pathol. 2013 Nov 15;6(12):2896-903.

10. You CE et al. Ann Dermatol. 2016 Oct;28(5):593-9. doi: 10.5021/ad.2016.28.5.593.

11. Shin D et al. Toxins (Basel). 2018 Apr 2;10(4):146. doi: 10.3390/toxins10040146.

12. Gu H et al. Mol Med Rep. 2018 Oct;18(4):3711-8. doi: 10.3892/mmr.2018.9398.

13. An HJ et al. Br J Pharmacol. 2018 Dec;175(23):4310-24. doi: 10.1111/bph.14487.

14. Han SM et al. J Integr Med. 2013 Sep;11(5):320-6. doi: 10.3736/jintegrmed2013043.

15. An HJ et al. Int J Mol Med. 2014 Nov;34(5):1341-8. doi: 10.3892/ijmm.2014.1933.

16. Kim JY et al. Int J Mol Med. 2015 Jun;35(6):1651-6. doi: 10.3892/ijmm.2015.2180.

17. Cao H et al. Cochrane Database Syst Rev. 2015 Jan 19;1:CD009436. doi: 10.1002/14651858.CD009436.pub2.

Key clinical point: In 10-year follow-up of ENESTnd trial, nilotinib demonstrated benefits over imatinib for various clinical outcomes in patients with newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP).

Major finding: Cumulative 10-year rates of treatment-free remission eligibility and molecular response rate with nilotinib 300 mg and 400 mg vs. imatinib was 48.6% and 47.3% vs. 29.7% and 77.7% and 79.7% vs. 62.5%, respectively. Progression to accelerated (6 and 4 vs. 11) or blast (6 and 6 vs. 14) phase was lower with nilotinib 300 mg and 400 mg vs. imatinib, respectively. Overall, the frequency of adverse events was similar, but rates of cardiovascular events were higher with nilotinib.

Study details: ENESTnd, a phase 3 study, randomly allocated patients with newly diagnosed CML-CP to receive nilotinib 300 mg twice daily (n=282), nilotinib 400 mg twice daily (n=281), or imatinib 400 mg once daily (n=283).

Disclosures: The study was funded by Novartis Pharmaceuticals Corporation. The presenting author reported ties with Pharmaceuticals companies including Novartis. Some of the study investigators reported being an employee of, receiving grants, honoraria, support, and/or consulting for Novartis and other pharmaceutical companies.

Source: Kantarjian HM et al. Leukemia. 2021 Jan 7. doi: 10.1038/s41375-020-01111-2.

Key clinical point: In 10-year follow-up of ENESTnd trial, nilotinib demonstrated benefits over imatinib for various clinical outcomes in patients with newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP).

Major finding: Cumulative 10-year rates of treatment-free remission eligibility and molecular response rate with nilotinib 300 mg and 400 mg vs. imatinib was 48.6% and 47.3% vs. 29.7% and 77.7% and 79.7% vs. 62.5%, respectively. Progression to accelerated (6 and 4 vs. 11) or blast (6 and 6 vs. 14) phase was lower with nilotinib 300 mg and 400 mg vs. imatinib, respectively. Overall, the frequency of adverse events was similar, but rates of cardiovascular events were higher with nilotinib.

Study details: ENESTnd, a phase 3 study, randomly allocated patients with newly diagnosed CML-CP to receive nilotinib 300 mg twice daily (n=282), nilotinib 400 mg twice daily (n=281), or imatinib 400 mg once daily (n=283).

Disclosures: The study was funded by Novartis Pharmaceuticals Corporation. The presenting author reported ties with Pharmaceuticals companies including Novartis. Some of the study investigators reported being an employee of, receiving grants, honoraria, support, and/or consulting for Novartis and other pharmaceutical companies.

Source: Kantarjian HM et al. Leukemia. 2021 Jan 7. doi: 10.1038/s41375-020-01111-2.

Key clinical point: In 10-year follow-up of ENESTnd trial, nilotinib demonstrated benefits over imatinib for various clinical outcomes in patients with newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP).

Major finding: Cumulative 10-year rates of treatment-free remission eligibility and molecular response rate with nilotinib 300 mg and 400 mg vs. imatinib was 48.6% and 47.3% vs. 29.7% and 77.7% and 79.7% vs. 62.5%, respectively. Progression to accelerated (6 and 4 vs. 11) or blast (6 and 6 vs. 14) phase was lower with nilotinib 300 mg and 400 mg vs. imatinib, respectively. Overall, the frequency of adverse events was similar, but rates of cardiovascular events were higher with nilotinib.

Study details: ENESTnd, a phase 3 study, randomly allocated patients with newly diagnosed CML-CP to receive nilotinib 300 mg twice daily (n=282), nilotinib 400 mg twice daily (n=281), or imatinib 400 mg once daily (n=283).

Disclosures: The study was funded by Novartis Pharmaceuticals Corporation. The presenting author reported ties with Pharmaceuticals companies including Novartis. Some of the study investigators reported being an employee of, receiving grants, honoraria, support, and/or consulting for Novartis and other pharmaceutical companies.

Source: Kantarjian HM et al. Leukemia. 2021 Jan 7. doi: 10.1038/s41375-020-01111-2.

Key clinical point: Patients with chronic myeloid leukemia (CML) in the era of tyrosine kinase inhibitors (TKIs) are at a greater risk for adverse cardiovascular events (ACEs) compared with the general population.

Major finding: From 2001 onwards, the risk for major ACEs (subdistribution hazard ratio [SHR], 1.27; 95% confidence interval [CI], 0.96-1.43) and cardiovascular death (SHR, 0.99; 95% CI, 0.84-1.18) was similar between patients with vs. without CML. However, before 2001, the risk for major ACE (SHR, 0.59; 95% CI, 0.46-0.76) and cardiovascular death (SHR, 0.43; 95% CI, 0.36-0.52) was lower in patients with vs. without CML.

Study details: A population-based retrospective study of 4,238 patients with CML who were age- and sex-matched with 42,380 controls without CML.

Disclosures: The study was funded by the Population Health Research Institute, McMaster University, and Institute of Clinical and Evaluative Sciences. The authors reported no conflicts of interest.

Source: Leong D et al. Heart. 2021 Jan 8. doi: 10.1136/heartjnl-2020-318251.

Key clinical point: Patients with chronic myeloid leukemia (CML) in the era of tyrosine kinase inhibitors (TKIs) are at a greater risk for adverse cardiovascular events (ACEs) compared with the general population.

Major finding: From 2001 onwards, the risk for major ACEs (subdistribution hazard ratio [SHR], 1.27; 95% confidence interval [CI], 0.96-1.43) and cardiovascular death (SHR, 0.99; 95% CI, 0.84-1.18) was similar between patients with vs. without CML. However, before 2001, the risk for major ACE (SHR, 0.59; 95% CI, 0.46-0.76) and cardiovascular death (SHR, 0.43; 95% CI, 0.36-0.52) was lower in patients with vs. without CML.

Study details: A population-based retrospective study of 4,238 patients with CML who were age- and sex-matched with 42,380 controls without CML.

Disclosures: The study was funded by the Population Health Research Institute, McMaster University, and Institute of Clinical and Evaluative Sciences. The authors reported no conflicts of interest.

Source: Leong D et al. Heart. 2021 Jan 8. doi: 10.1136/heartjnl-2020-318251.

Key clinical point: Patients with chronic myeloid leukemia (CML) in the era of tyrosine kinase inhibitors (TKIs) are at a greater risk for adverse cardiovascular events (ACEs) compared with the general population.

Major finding: From 2001 onwards, the risk for major ACEs (subdistribution hazard ratio [SHR], 1.27; 95% confidence interval [CI], 0.96-1.43) and cardiovascular death (SHR, 0.99; 95% CI, 0.84-1.18) was similar between patients with vs. without CML. However, before 2001, the risk for major ACE (SHR, 0.59; 95% CI, 0.46-0.76) and cardiovascular death (SHR, 0.43; 95% CI, 0.36-0.52) was lower in patients with vs. without CML.

Study details: A population-based retrospective study of 4,238 patients with CML who were age- and sex-matched with 42,380 controls without CML.

Disclosures: The study was funded by the Population Health Research Institute, McMaster University, and Institute of Clinical and Evaluative Sciences. The authors reported no conflicts of interest.

Source: Leong D et al. Heart. 2021 Jan 8. doi: 10.1136/heartjnl-2020-318251.

Key clinical point: High levels of cholesterol plasma and low-density lipoprotein (LDL) after 3 months of nilotinib initiation were associated with a higher risk for arterial occlusive events (AOEs) in patients with chronic myeloid leukemia (CML).

Major finding: Cholesterol plasma level greater than 200 mg/dL and LDL greater than 70 mg/dL after 3 months since nilotinib initiation was associated with a significantly higher risk of AOEs (hazard ratio, 3.5; P = .008).

Study details: Findings are from a retrospective study of 369 patients with CML treated with nilotinib.

Disclosures: The study was performed within the framework of the research project funded by P.O.R. SARDEGNA F.S.E. 2014-2020 - Asse III. The authors declared no conflicts of interest.

Source: Caocci G et al. Ann Hematol. 2021 Jan 3. doi: 10.1007/s00277-020-04392-w.

Key clinical point: High levels of cholesterol plasma and low-density lipoprotein (LDL) after 3 months of nilotinib initiation were associated with a higher risk for arterial occlusive events (AOEs) in patients with chronic myeloid leukemia (CML).

Major finding: Cholesterol plasma level greater than 200 mg/dL and LDL greater than 70 mg/dL after 3 months since nilotinib initiation was associated with a significantly higher risk of AOEs (hazard ratio, 3.5; P = .008).

Study details: Findings are from a retrospective study of 369 patients with CML treated with nilotinib.

Disclosures: The study was performed within the framework of the research project funded by P.O.R. SARDEGNA F.S.E. 2014-2020 - Asse III. The authors declared no conflicts of interest.

Source: Caocci G et al. Ann Hematol. 2021 Jan 3. doi: 10.1007/s00277-020-04392-w.

Key clinical point: High levels of cholesterol plasma and low-density lipoprotein (LDL) after 3 months of nilotinib initiation were associated with a higher risk for arterial occlusive events (AOEs) in patients with chronic myeloid leukemia (CML).

Major finding: Cholesterol plasma level greater than 200 mg/dL and LDL greater than 70 mg/dL after 3 months since nilotinib initiation was associated with a significantly higher risk of AOEs (hazard ratio, 3.5; P = .008).

Study details: Findings are from a retrospective study of 369 patients with CML treated with nilotinib.

Disclosures: The study was performed within the framework of the research project funded by P.O.R. SARDEGNA F.S.E. 2014-2020 - Asse III. The authors declared no conflicts of interest.

Source: Caocci G et al. Ann Hematol. 2021 Jan 3. doi: 10.1007/s00277-020-04392-w.