MDedge ObGyn

In outpatients with COVID-19, peginterferon lambda has the potential to prevent clinical deterioration and shorten the duration of viral shedding, according to results of a double-blind, placebo-controlled trial (NCT04354259).

Reductions in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA were greater with peginterferon lambda than with placebo from day 3 onward in the phase 2 study led by Jordan J. Feld, MD, of the Toronto Centre for Liver Disease. The findings were reported in The Lancet Respiratory Medicine.
 

Fewer side effects

To date in randomized clinical trials, efficacy in treatment of COVID-19 has been shown only for remdesivir and dexamethasone in hospitalized patients, and in an interim analysis of accelerated viral clearance for a monoclonal antibody infusion in outpatients.

Activity against respiratory pathogens has been demonstrated for interferon lambda-1, a type III interferon shown to be involved in innate antiviral responses. Interferons, Dr. Feld and coauthors stated, drive induction of genes with antiviral, antiproliferative and immunoregulatory properties, and early treatment with interferons might halt clinical progression and shorten the duration of viral shedding with reduced onward transmission. In addition, interferon lambdas (type III) use a distinct receptor complex with high expression levels limited to epithelial cells in the lung, liver, and intestine, leading to fewer side effects than other interferons, including avoiding risk of promoting cytokine storm syndrome.

The researchers investigated peginterferon lambda safety and efficacy in treatment of patients with laboratory-confirmed, mild to moderate COVID-19. Sixty patients (median age 46 years, about 60% female, about 50% White) were recruited from outpatient testing centers at six institutions in Toronto, and referred to a single ambulatory site. Patients were randomly assigned 1:1 to a single subcutaneous injection of peginterferon lambda 180 mcg or placebo within 7 days of symptom onset or, if asymptomatic, of their first positive swab. Mean time from symptom onset to injection was about 4.5 days, and about 18.5% were asymptomatic. The primary outcome was the proportion of patients negative for SARS-CoV-2 RNA on day 7 after the injection.
 

Greater benefit with higher baseline load

A higher baseline SARS-CoV-2 RNA concentration found in the peginterferon lambda group was found to be significantly associated with day 7 clearance (odds ratio [OR] 0.69 [95% confidence interval 0.51-0.87]; P = ·001). In the peginterferon lambda group, also, the mean decline in SARS-CoV-2 RNA was significantly larger than in the placebo group across all time points (days 3, 5, 7, and14). While viral load decline was 0.81 log greater in the treatment group (P = .14) by day 3, viral load decline increased to 1.67 log copies per mL by day 5 (P = .013) and 2.42 log copies per mL by day 7 (P = .0041). At day 14, the viral decline was 1.77 log copies per mL larger in the peginterferon lambda group (P = .048). The investigators pointed out that the difference in viral load decline between groups was greater in patients with high baseline viral load (at or above 106 copies per mL). In the peginterferon lambda high baseline viral load group, the reduction was 7.17 log copies per mL, versus 4.92 log copies per mL in the placebo group (P = .004).
 

More patients SARS-CoV-2 RNA negative

By day 7, 80% of patients in the peginterferon lambda group were negative for SARS-CoV-2 RNA, compared with 63% in the placebo group (P = .15). After baseline load adjustment, however, the peginterferon lambda treatment was significantly associated with day 7 clearance (OR 4·12 [95% CI 1·15-16·73]; P = .029).
 

Respiratory symptoms improved faster

Most symptoms in both groups were mild to moderate, without difference in frequency or severity. While symptom improvement was generally similar over time for both groups, respiratory symptoms improved faster with peginterferon lambda, with the effect more pronounced in the high baseline viral load group (OR 5·88 (0·81-42·46; P =. 079).

Laboratory adverse events, similar for both groups, were mild.

“Peginterferon lambda has potential to prevent clinical deterioration and shorten duration of viral shedding,” the investigators concluded.

“This clinical trial is important” because it suggests that a single intravenous dose of peginterferon lambda administered to outpatients with a positive SARS-CoV-2 nasopharyngeal swab speeds reduction of SARS-CoV-2 viral load, David L. Bowton, MD, FCCP, professor emeritus, Wake Forest Baptist Health, Winston-Salem, N.C., said in an interview. He observed that the smaller viral load difference observed at day 14 likely reflects host immune responses.

Dr. Bowton also noted that two placebo group baseline characteristics (five placebo group patients with anti-SARS-CoV-2 S protein IgG antibodies; two times more undetectable SARS-CoV-2 RNA at baseline assessment) would tend to reduce differences between the peginterferon lambda and placebo groups. He added that the study findings were concordant with another phase 2 trial of hospitalized COVID-19 patients receiving inhaled interferon beta-1a.

“Thus, interferons may find a place in the treatment of COVID-19 and perhaps other severe viral illnesses,” Dr. Bowton said.

The study was funded by the Toronto COVID-19 Action Initiative, University of Toronto, and the Ontario First COVID-19 Rapid Research Fund, Toronto General & Western Hospital Foundation.

Dr. Bowton had no disclosures. Disclosures for Dr. Feld and coauthors are listed on the Lancet Respiratory Medicine website.

In outpatients with COVID-19, peginterferon lambda has the potential to prevent clinical deterioration and shorten the duration of viral shedding, according to results of a double-blind, placebo-controlled trial (NCT04354259).

Reductions in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA were greater with peginterferon lambda than with placebo from day 3 onward in the phase 2 study led by Jordan J. Feld, MD, of the Toronto Centre for Liver Disease. The findings were reported in The Lancet Respiratory Medicine.
 

Fewer side effects

To date in randomized clinical trials, efficacy in treatment of COVID-19 has been shown only for remdesivir and dexamethasone in hospitalized patients, and in an interim analysis of accelerated viral clearance for a monoclonal antibody infusion in outpatients.

Activity against respiratory pathogens has been demonstrated for interferon lambda-1, a type III interferon shown to be involved in innate antiviral responses. Interferons, Dr. Feld and coauthors stated, drive induction of genes with antiviral, antiproliferative and immunoregulatory properties, and early treatment with interferons might halt clinical progression and shorten the duration of viral shedding with reduced onward transmission. In addition, interferon lambdas (type III) use a distinct receptor complex with high expression levels limited to epithelial cells in the lung, liver, and intestine, leading to fewer side effects than other interferons, including avoiding risk of promoting cytokine storm syndrome.

The researchers investigated peginterferon lambda safety and efficacy in treatment of patients with laboratory-confirmed, mild to moderate COVID-19. Sixty patients (median age 46 years, about 60% female, about 50% White) were recruited from outpatient testing centers at six institutions in Toronto, and referred to a single ambulatory site. Patients were randomly assigned 1:1 to a single subcutaneous injection of peginterferon lambda 180 mcg or placebo within 7 days of symptom onset or, if asymptomatic, of their first positive swab. Mean time from symptom onset to injection was about 4.5 days, and about 18.5% were asymptomatic. The primary outcome was the proportion of patients negative for SARS-CoV-2 RNA on day 7 after the injection.
 

Greater benefit with higher baseline load

A higher baseline SARS-CoV-2 RNA concentration found in the peginterferon lambda group was found to be significantly associated with day 7 clearance (odds ratio [OR] 0.69 [95% confidence interval 0.51-0.87]; P = ·001). In the peginterferon lambda group, also, the mean decline in SARS-CoV-2 RNA was significantly larger than in the placebo group across all time points (days 3, 5, 7, and14). While viral load decline was 0.81 log greater in the treatment group (P = .14) by day 3, viral load decline increased to 1.67 log copies per mL by day 5 (P = .013) and 2.42 log copies per mL by day 7 (P = .0041). At day 14, the viral decline was 1.77 log copies per mL larger in the peginterferon lambda group (P = .048). The investigators pointed out that the difference in viral load decline between groups was greater in patients with high baseline viral load (at or above 106 copies per mL). In the peginterferon lambda high baseline viral load group, the reduction was 7.17 log copies per mL, versus 4.92 log copies per mL in the placebo group (P = .004).
 

More patients SARS-CoV-2 RNA negative

By day 7, 80% of patients in the peginterferon lambda group were negative for SARS-CoV-2 RNA, compared with 63% in the placebo group (P = .15). After baseline load adjustment, however, the peginterferon lambda treatment was significantly associated with day 7 clearance (OR 4·12 [95% CI 1·15-16·73]; P = .029).
 

Respiratory symptoms improved faster

Most symptoms in both groups were mild to moderate, without difference in frequency or severity. While symptom improvement was generally similar over time for both groups, respiratory symptoms improved faster with peginterferon lambda, with the effect more pronounced in the high baseline viral load group (OR 5·88 (0·81-42·46; P =. 079).

Laboratory adverse events, similar for both groups, were mild.

“Peginterferon lambda has potential to prevent clinical deterioration and shorten duration of viral shedding,” the investigators concluded.

“This clinical trial is important” because it suggests that a single intravenous dose of peginterferon lambda administered to outpatients with a positive SARS-CoV-2 nasopharyngeal swab speeds reduction of SARS-CoV-2 viral load, David L. Bowton, MD, FCCP, professor emeritus, Wake Forest Baptist Health, Winston-Salem, N.C., said in an interview. He observed that the smaller viral load difference observed at day 14 likely reflects host immune responses.

Dr. Bowton also noted that two placebo group baseline characteristics (five placebo group patients with anti-SARS-CoV-2 S protein IgG antibodies; two times more undetectable SARS-CoV-2 RNA at baseline assessment) would tend to reduce differences between the peginterferon lambda and placebo groups. He added that the study findings were concordant with another phase 2 trial of hospitalized COVID-19 patients receiving inhaled interferon beta-1a.

“Thus, interferons may find a place in the treatment of COVID-19 and perhaps other severe viral illnesses,” Dr. Bowton said.

The study was funded by the Toronto COVID-19 Action Initiative, University of Toronto, and the Ontario First COVID-19 Rapid Research Fund, Toronto General & Western Hospital Foundation.

Dr. Bowton had no disclosures. Disclosures for Dr. Feld and coauthors are listed on the Lancet Respiratory Medicine website.

In outpatients with COVID-19, peginterferon lambda has the potential to prevent clinical deterioration and shorten the duration of viral shedding, according to results of a double-blind, placebo-controlled trial (NCT04354259).

Reductions in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA were greater with peginterferon lambda than with placebo from day 3 onward in the phase 2 study led by Jordan J. Feld, MD, of the Toronto Centre for Liver Disease. The findings were reported in The Lancet Respiratory Medicine.
 

Fewer side effects

To date in randomized clinical trials, efficacy in treatment of COVID-19 has been shown only for remdesivir and dexamethasone in hospitalized patients, and in an interim analysis of accelerated viral clearance for a monoclonal antibody infusion in outpatients.

Activity against respiratory pathogens has been demonstrated for interferon lambda-1, a type III interferon shown to be involved in innate antiviral responses. Interferons, Dr. Feld and coauthors stated, drive induction of genes with antiviral, antiproliferative and immunoregulatory properties, and early treatment with interferons might halt clinical progression and shorten the duration of viral shedding with reduced onward transmission. In addition, interferon lambdas (type III) use a distinct receptor complex with high expression levels limited to epithelial cells in the lung, liver, and intestine, leading to fewer side effects than other interferons, including avoiding risk of promoting cytokine storm syndrome.

The researchers investigated peginterferon lambda safety and efficacy in treatment of patients with laboratory-confirmed, mild to moderate COVID-19. Sixty patients (median age 46 years, about 60% female, about 50% White) were recruited from outpatient testing centers at six institutions in Toronto, and referred to a single ambulatory site. Patients were randomly assigned 1:1 to a single subcutaneous injection of peginterferon lambda 180 mcg or placebo within 7 days of symptom onset or, if asymptomatic, of their first positive swab. Mean time from symptom onset to injection was about 4.5 days, and about 18.5% were asymptomatic. The primary outcome was the proportion of patients negative for SARS-CoV-2 RNA on day 7 after the injection.
 

Greater benefit with higher baseline load

A higher baseline SARS-CoV-2 RNA concentration found in the peginterferon lambda group was found to be significantly associated with day 7 clearance (odds ratio [OR] 0.69 [95% confidence interval 0.51-0.87]; P = ·001). In the peginterferon lambda group, also, the mean decline in SARS-CoV-2 RNA was significantly larger than in the placebo group across all time points (days 3, 5, 7, and14). While viral load decline was 0.81 log greater in the treatment group (P = .14) by day 3, viral load decline increased to 1.67 log copies per mL by day 5 (P = .013) and 2.42 log copies per mL by day 7 (P = .0041). At day 14, the viral decline was 1.77 log copies per mL larger in the peginterferon lambda group (P = .048). The investigators pointed out that the difference in viral load decline between groups was greater in patients with high baseline viral load (at or above 106 copies per mL). In the peginterferon lambda high baseline viral load group, the reduction was 7.17 log copies per mL, versus 4.92 log copies per mL in the placebo group (P = .004).
 

More patients SARS-CoV-2 RNA negative

By day 7, 80% of patients in the peginterferon lambda group were negative for SARS-CoV-2 RNA, compared with 63% in the placebo group (P = .15). After baseline load adjustment, however, the peginterferon lambda treatment was significantly associated with day 7 clearance (OR 4·12 [95% CI 1·15-16·73]; P = .029).
 

Respiratory symptoms improved faster

Most symptoms in both groups were mild to moderate, without difference in frequency or severity. While symptom improvement was generally similar over time for both groups, respiratory symptoms improved faster with peginterferon lambda, with the effect more pronounced in the high baseline viral load group (OR 5·88 (0·81-42·46; P =. 079).

Laboratory adverse events, similar for both groups, were mild.

“Peginterferon lambda has potential to prevent clinical deterioration and shorten duration of viral shedding,” the investigators concluded.

“This clinical trial is important” because it suggests that a single intravenous dose of peginterferon lambda administered to outpatients with a positive SARS-CoV-2 nasopharyngeal swab speeds reduction of SARS-CoV-2 viral load, David L. Bowton, MD, FCCP, professor emeritus, Wake Forest Baptist Health, Winston-Salem, N.C., said in an interview. He observed that the smaller viral load difference observed at day 14 likely reflects host immune responses.

Dr. Bowton also noted that two placebo group baseline characteristics (five placebo group patients with anti-SARS-CoV-2 S protein IgG antibodies; two times more undetectable SARS-CoV-2 RNA at baseline assessment) would tend to reduce differences between the peginterferon lambda and placebo groups. He added that the study findings were concordant with another phase 2 trial of hospitalized COVID-19 patients receiving inhaled interferon beta-1a.

“Thus, interferons may find a place in the treatment of COVID-19 and perhaps other severe viral illnesses,” Dr. Bowton said.

The study was funded by the Toronto COVID-19 Action Initiative, University of Toronto, and the Ontario First COVID-19 Rapid Research Fund, Toronto General & Western Hospital Foundation.

Dr. Bowton had no disclosures. Disclosures for Dr. Feld and coauthors are listed on the Lancet Respiratory Medicine website.

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.

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.

An analysis of data from the U.S. military suggests that the maternal morbidity disparities between Black and White women cannot be attributed solely to differences in access to care and socioeconomics.

Even in the U.S. military health care system, where all service members have universal access to the same facilities and providers, researchers found substantial racial disparities in cesarean deliveries, maternal ICU admission, and overall severe maternal morbidity and mortality between Black patients and White patients, according to findings from a new study presented Jan. 28, 2021, at a meeting sponsored by the Society for Maternal-Fetal Medicine.

“This was surprising given some of the driving theories behind maternal race disparities encountered in this country, such as access to care and socioeconomic status, are controlled for in this health care system,” Capt. Jameaka Hamilton, MD, who presented the research, said in an interview. “Our findings indicate that there are likely additional factors at play which impact the obstetrical outcomes of women based upon their race, including systems-based barriers to accessing the military health care system which contribute to health care disparities, or in systemic or implicit biases which occur within our health care delivery.”

Plenty of recent research has documented the rise in maternal morbidity and mortality in the United States and the considerable racial disparities within those statistics. Black women are twice as likely to suffer morbidity and three to four times more likely to die in childbirth, compared with White women, Dr. Hamilton, an ob.gyn. from the San Antonio Uniformed Services Health Education Consortium at Ft. Sam Houston in San Antonio, Texas, reminded attendees. So far, much of this disparity has been attributed to social determinants of health.

Military retirees, active-duty personnel, and dependents, however, have equal access to federal health insurance and care at military health care facilities, or at covered civilian facilities where needed. Hence the researchers’ hypothesis that the military medical system would not show the same disparities by race that are seen in civilian populations.

The researchers analyzed maternal morbidity data from the Neonatal Perinatal Information Center from April 2018 to March 2019. The retrospective study included data from 13 military treatment facilities that had more than 1,000 deliveries per year. In addition to statistics on cesarean delivery and adult ICU admission, the researchers compared numbers on overall severe maternal morbidity based on the indicators defined by the Centers for Disease Control and Prevention.

The 15,305 deliveries included 23% Black patients and 77% White patients from the Air Force, Army, and Navy branches.

The cesarean delivery rate ranged from 19.4% to 35.5%. ICU admissions totaled 38 women, 190 women had postpartum hemorrhage, and 282 women experienced severe maternal morbidity. All three measures revealed racial disparities:

• Overall severe maternal morbidity occurred in 2.66% of Black women and 1.66% of White women (P =.0001).
• ICU admission occurred in 0.49% of Black women and 0.18% of White women (P =.0026).
• 31.68% of Black women had a cesarean delivery, compared with 23.58% of White women (P <.0001).

After excluding cases with blood transfusions, Black women were twice as likely to have severe maternal morbidity (0.64% vs. 0.32%). There were no significant differences in postpartum hemorrhage rates between Black and White women, but this analysis was limited by the small overall numbers of postpartum hemorrhage.

Among the study’s limitations were the inability to stratify patients by retiree, active duty, or dependent status, and the lack of data on preeclampsia rates, maternal age, obesity, or other preexisting conditions. In addition, the initial dataset included 61% of patients who reported their race as “other” than Black or White, limiting the number of patients whose data could be analyzed. Since low-volume hospitals were excluded, the outcomes could be skewed if lower-volume facilities are more likely to care for more complex cases, Dr. Hamilton added.

Allison Bryant Mantha, MD, MPH, vice chair for quality, equity, and safety in the ob.gyn. department at Massachusetts General Hospital, Boston, praised Dr. Hamilton’s work for revealing that differential access – though still problematic – cannot fully explain inequities between Black women and other women.

“The findings are not shocking given that what underlies some of these inequities – namely structural and institutional racism, and differential treatment within the system – are not exclusive to civilian health care settings,” Dr. Bryant Mantha, who moderated the session, said in an interview. “That said, doing the work to demonstrate this is extremely valuable.”

Although the causes of these disparities are systemic, Dr. Hamilton said individual providers can play a role in addressing them.

“There can certainly be more done to address this dangerous trend at the provider, hospital/institution, and national level,” she said. I think we as providers should continue to self-reflect and address our own biases. Hospitals and institutions should continue to develop policies that draw attention health care disparities.”

Completely removing these inequalities, however, will require confronting the racism embedded in U.S. health care at all levels, Dr. Bryant Mantha suggested.

“Ultimately, moving to an antiracist health care system – and criminal justice system, educational system, political system, etc. – and dismantling the existing structural racism in policies and practices will be needed to drive this change,” Dr. Bryant Mantha said. “Individual clinicians can use their voices to advocate for these changes in their health systems, communities, and states. Awareness of these inequities is critical, as is a sense of collective efficacy that we can, indeed, change the status quo.”

Dr. Hamilton and Dr. Bryant Mantha reported no disclosures.

An analysis of data from the U.S. military suggests that the maternal morbidity disparities between Black and White women cannot be attributed solely to differences in access to care and socioeconomics.

Even in the U.S. military health care system, where all service members have universal access to the same facilities and providers, researchers found substantial racial disparities in cesarean deliveries, maternal ICU admission, and overall severe maternal morbidity and mortality between Black patients and White patients, according to findings from a new study presented Jan. 28, 2021, at a meeting sponsored by the Society for Maternal-Fetal Medicine.

“This was surprising given some of the driving theories behind maternal race disparities encountered in this country, such as access to care and socioeconomic status, are controlled for in this health care system,” Capt. Jameaka Hamilton, MD, who presented the research, said in an interview. “Our findings indicate that there are likely additional factors at play which impact the obstetrical outcomes of women based upon their race, including systems-based barriers to accessing the military health care system which contribute to health care disparities, or in systemic or implicit biases which occur within our health care delivery.”

Plenty of recent research has documented the rise in maternal morbidity and mortality in the United States and the considerable racial disparities within those statistics. Black women are twice as likely to suffer morbidity and three to four times more likely to die in childbirth, compared with White women, Dr. Hamilton, an ob.gyn. from the San Antonio Uniformed Services Health Education Consortium at Ft. Sam Houston in San Antonio, Texas, reminded attendees. So far, much of this disparity has been attributed to social determinants of health.

Military retirees, active-duty personnel, and dependents, however, have equal access to federal health insurance and care at military health care facilities, or at covered civilian facilities where needed. Hence the researchers’ hypothesis that the military medical system would not show the same disparities by race that are seen in civilian populations.

The researchers analyzed maternal morbidity data from the Neonatal Perinatal Information Center from April 2018 to March 2019. The retrospective study included data from 13 military treatment facilities that had more than 1,000 deliveries per year. In addition to statistics on cesarean delivery and adult ICU admission, the researchers compared numbers on overall severe maternal morbidity based on the indicators defined by the Centers for Disease Control and Prevention.

The 15,305 deliveries included 23% Black patients and 77% White patients from the Air Force, Army, and Navy branches.

The cesarean delivery rate ranged from 19.4% to 35.5%. ICU admissions totaled 38 women, 190 women had postpartum hemorrhage, and 282 women experienced severe maternal morbidity. All three measures revealed racial disparities:

• Overall severe maternal morbidity occurred in 2.66% of Black women and 1.66% of White women (P =.0001).
• ICU admission occurred in 0.49% of Black women and 0.18% of White women (P =.0026).
• 31.68% of Black women had a cesarean delivery, compared with 23.58% of White women (P <.0001).

After excluding cases with blood transfusions, Black women were twice as likely to have severe maternal morbidity (0.64% vs. 0.32%). There were no significant differences in postpartum hemorrhage rates between Black and White women, but this analysis was limited by the small overall numbers of postpartum hemorrhage.

Among the study’s limitations were the inability to stratify patients by retiree, active duty, or dependent status, and the lack of data on preeclampsia rates, maternal age, obesity, or other preexisting conditions. In addition, the initial dataset included 61% of patients who reported their race as “other” than Black or White, limiting the number of patients whose data could be analyzed. Since low-volume hospitals were excluded, the outcomes could be skewed if lower-volume facilities are more likely to care for more complex cases, Dr. Hamilton added.

Allison Bryant Mantha, MD, MPH, vice chair for quality, equity, and safety in the ob.gyn. department at Massachusetts General Hospital, Boston, praised Dr. Hamilton’s work for revealing that differential access – though still problematic – cannot fully explain inequities between Black women and other women.

“The findings are not shocking given that what underlies some of these inequities – namely structural and institutional racism, and differential treatment within the system – are not exclusive to civilian health care settings,” Dr. Bryant Mantha, who moderated the session, said in an interview. “That said, doing the work to demonstrate this is extremely valuable.”

Although the causes of these disparities are systemic, Dr. Hamilton said individual providers can play a role in addressing them.

“There can certainly be more done to address this dangerous trend at the provider, hospital/institution, and national level,” she said. I think we as providers should continue to self-reflect and address our own biases. Hospitals and institutions should continue to develop policies that draw attention health care disparities.”

Completely removing these inequalities, however, will require confronting the racism embedded in U.S. health care at all levels, Dr. Bryant Mantha suggested.

“Ultimately, moving to an antiracist health care system – and criminal justice system, educational system, political system, etc. – and dismantling the existing structural racism in policies and practices will be needed to drive this change,” Dr. Bryant Mantha said. “Individual clinicians can use their voices to advocate for these changes in their health systems, communities, and states. Awareness of these inequities is critical, as is a sense of collective efficacy that we can, indeed, change the status quo.”

Dr. Hamilton and Dr. Bryant Mantha reported no disclosures.

An analysis of data from the U.S. military suggests that the maternal morbidity disparities between Black and White women cannot be attributed solely to differences in access to care and socioeconomics.

Even in the U.S. military health care system, where all service members have universal access to the same facilities and providers, researchers found substantial racial disparities in cesarean deliveries, maternal ICU admission, and overall severe maternal morbidity and mortality between Black patients and White patients, according to findings from a new study presented Jan. 28, 2021, at a meeting sponsored by the Society for Maternal-Fetal Medicine.

“This was surprising given some of the driving theories behind maternal race disparities encountered in this country, such as access to care and socioeconomic status, are controlled for in this health care system,” Capt. Jameaka Hamilton, MD, who presented the research, said in an interview. “Our findings indicate that there are likely additional factors at play which impact the obstetrical outcomes of women based upon their race, including systems-based barriers to accessing the military health care system which contribute to health care disparities, or in systemic or implicit biases which occur within our health care delivery.”

Plenty of recent research has documented the rise in maternal morbidity and mortality in the United States and the considerable racial disparities within those statistics. Black women are twice as likely to suffer morbidity and three to four times more likely to die in childbirth, compared with White women, Dr. Hamilton, an ob.gyn. from the San Antonio Uniformed Services Health Education Consortium at Ft. Sam Houston in San Antonio, Texas, reminded attendees. So far, much of this disparity has been attributed to social determinants of health.

Military retirees, active-duty personnel, and dependents, however, have equal access to federal health insurance and care at military health care facilities, or at covered civilian facilities where needed. Hence the researchers’ hypothesis that the military medical system would not show the same disparities by race that are seen in civilian populations.

The researchers analyzed maternal morbidity data from the Neonatal Perinatal Information Center from April 2018 to March 2019. The retrospective study included data from 13 military treatment facilities that had more than 1,000 deliveries per year. In addition to statistics on cesarean delivery and adult ICU admission, the researchers compared numbers on overall severe maternal morbidity based on the indicators defined by the Centers for Disease Control and Prevention.

The 15,305 deliveries included 23% Black patients and 77% White patients from the Air Force, Army, and Navy branches.

The cesarean delivery rate ranged from 19.4% to 35.5%. ICU admissions totaled 38 women, 190 women had postpartum hemorrhage, and 282 women experienced severe maternal morbidity. All three measures revealed racial disparities:

• Overall severe maternal morbidity occurred in 2.66% of Black women and 1.66% of White women (P =.0001).
• ICU admission occurred in 0.49% of Black women and 0.18% of White women (P =.0026).
• 31.68% of Black women had a cesarean delivery, compared with 23.58% of White women (P <.0001).

After excluding cases with blood transfusions, Black women were twice as likely to have severe maternal morbidity (0.64% vs. 0.32%). There were no significant differences in postpartum hemorrhage rates between Black and White women, but this analysis was limited by the small overall numbers of postpartum hemorrhage.

Among the study’s limitations were the inability to stratify patients by retiree, active duty, or dependent status, and the lack of data on preeclampsia rates, maternal age, obesity, or other preexisting conditions. In addition, the initial dataset included 61% of patients who reported their race as “other” than Black or White, limiting the number of patients whose data could be analyzed. Since low-volume hospitals were excluded, the outcomes could be skewed if lower-volume facilities are more likely to care for more complex cases, Dr. Hamilton added.

Allison Bryant Mantha, MD, MPH, vice chair for quality, equity, and safety in the ob.gyn. department at Massachusetts General Hospital, Boston, praised Dr. Hamilton’s work for revealing that differential access – though still problematic – cannot fully explain inequities between Black women and other women.

“The findings are not shocking given that what underlies some of these inequities – namely structural and institutional racism, and differential treatment within the system – are not exclusive to civilian health care settings,” Dr. Bryant Mantha, who moderated the session, said in an interview. “That said, doing the work to demonstrate this is extremely valuable.”

Although the causes of these disparities are systemic, Dr. Hamilton said individual providers can play a role in addressing them.

“There can certainly be more done to address this dangerous trend at the provider, hospital/institution, and national level,” she said. I think we as providers should continue to self-reflect and address our own biases. Hospitals and institutions should continue to develop policies that draw attention health care disparities.”

Completely removing these inequalities, however, will require confronting the racism embedded in U.S. health care at all levels, Dr. Bryant Mantha suggested.

“Ultimately, moving to an antiracist health care system – and criminal justice system, educational system, political system, etc. – and dismantling the existing structural racism in policies and practices will be needed to drive this change,” Dr. Bryant Mantha said. “Individual clinicians can use their voices to advocate for these changes in their health systems, communities, and states. Awareness of these inequities is critical, as is a sense of collective efficacy that we can, indeed, change the status quo.”

Dr. Hamilton and Dr. Bryant Mantha reported no disclosures.

Many screening tools are available in the public domain to assess a variety of symptoms related to im­paired mental health. These tools can be used to quickly evaluate for mood, suicidal ide­ation or behavior, anxiety, sleep, substance use, pain, trauma, memory, and cognition (TABLE). Individuals with poor mental health incur high health care costs. Those suffering from anxiety and posttraumatic stress have more outpatient and emergency department visits and hospitalizations than patients with­out these disorders,^1,2 although use of mental health care services has been related to a de­crease in the overutilization of health care ser­vices in general.³

Here we review several screening tools that can help you to identify symptoms of mental illnesses and thus, provide prompt early intervention, including referrals to psy­chological and psychiatric services.

Mood disorders

Most patients with mood disorders are treated in primary care settings.⁴ Quickly measuring patients’ mood symptoms can expedite treat­ment for those who need it. Many primary care clinics use the 9-item Patient Health Question­naire (PHQ-9) to screen for depression.⁵ The US Preventive Services Task Force (USPSTF) has recommended screening for depression with adequate systems to ensure accurate diagnoses, effective treatment, and follow-up. Although the USPSTF did not specially endorse screening for bipolar disorder, it fol­lowed that recommendation with the qualify­ing statement, “positive screening results [for depression] should lead to additional assess­ment that considers severity of depression and comorbid psychological problems, alternate diagnoses, and medical conditions.”⁶ Thus, fol­lowing a positive screen result for depression, consider using a screening tool for mood dis­orders to provide diagnostic clarification.

The Mood Disorder Question­naire (MDQ) is a validated 15-item, self-administered questionnaire that takes only 5 minutes to use in screening adult patients for bipolar I disorder.⁷ The MDQ assesses specific behaviors related to bipolar disorder, symptom co-occurrence, and functional im­pairment. The MDQ has low sensitivity (58%) but good specificity (93%) in a primary care setting.⁸ However, the MDQ is not a diagnos­tic instrument. A positive screen result should prompt a more thorough clinical evaluation, if necessary, by a professional trained in psychi­atric disorders.

We recommend completing the MDQ pri­or to prescribing antidepressants. You can also monitor a patient’s response to treatment with serial MDQ testing. The MDQ is useful, too, when a patient has unclear mood symptoms that may have features overlapping with bi­polar disorder. Furthermore, we recommend screening for bipolar disorder with every patient who reports symptoms of depression, given that some pharmacologic treatments (predominately selective serotonin reuptake inhibitors) can induce mania in patients who actually have unrecognized bipolar disorder.⁹

Continue to: Suicide...

Suicide

Suicide is the 10th leading cause of death among the general population. All demo­graphic groups are impacted by suicide; how­ever, the most vulnerable are men ages 45 to 64 years.¹⁰ Given the imminent risk to indi­viduals who experience suicidal ideation, properly assessing and targeting suicidal risk is paramount.

The Columbia Suicide Severity Rating Scale (C-SSRS) can be completed in an inter­view format or as a patient self-report. Ver­sions of the C-SSRS are available for children, adolescents, and adults. It can be used in practice with any patient who may be at risk for suicide. Specifically, consider using the C-SSRS when a patient scores 1 or greater on the PHQ-9 or when risk is revealed with an­other brief screening tool that includes sui­cidal ideation.

The C-SSRS covers 10 categories related to suicidal ideation and behavior that the cli­nician explores with questions requiring only Yes/No responses. The C-SSRS demonstrates moderate-to-strong internal consistency and reliability, and it has shown a high degree of sensitivity (95%) and specificity (95%) for sui­cidal ideation.¹¹

Anxiety and physiologic arousal

Generalized anxiety disorder (GAD) is one of the most common anxiety disorders, with an estimated prevalence of 2.8% to 8.5% among primary care patients.¹² Brief, validated screening tools such as the Generalized Anxi­ety Disorder–7 item (GAD-7) scale can be ef­fective in identifying anxiety and other related disorders in primary care settings.

The GAD-7 comprises 7 items inquir­ing about symptoms experienced in the past 2 weeks. Scores range from 0 to 21, with cutoffs of 5, 10, and 15 indicating mild, moderate, and severe anxiety, respectively. This question­naire is appropriate for use with adults and has strong specificity, internal consistency, and test-retest reliability.¹² Specificity and sen­sitivity of the GAD-7 are maximized at a cutoff score of 10 or greater, both exceeding 80%.¹² The GAD-7 can be used when patients report symptoms of anxiety or when one needs to screen for anxiety with new patients or more clearly understand symptoms among patients who have complex mental health concerns.

The Screen for Child Anxiety Related Disorders (SCARED) is a 41-item self-report measure of anxiety for children ages 8 to 18. The SCARED questionnaire yields an overall anxiety score, as well as subscales for panic disorder or significant somatic symptoms, generalized anxiety disorder, separation anxi­ety, social anxiety disorder, and significant school avoidance.¹³ There is also a 5-item ver­sion of the SCARED, which can be useful for brief screening in fast-paced settings when no anxiety disorder is suspected, or for children who may have anxiety but exhibit reduced ver­bal capacity. The SCARED has been found to have moderate sensitivity (81.8%) and speci­ficity (52%) for diagnosing anxiety disorders in a community sample, with an optimal cutoff point of 22 on the total scale.¹⁴

Sleep

Sleep concerns are common, with the preva­lence of insomnia among adults in the United States estimated to be 19.2%.¹⁵ The importance of assessing these concerns cannot be over­stated, and primary care providers are the ones patients consult most often.¹⁶ The gold standard in assessing sleep disorders is a structured clinical interview, polysomnogra­phy, sleep diary, and actigraphy (home-based monitoring of movement through a device, often worn on the wrist).^17,18 However, this work-up is expensive, time-intensive, and im­practical in integrated care settings; thus the need for a brief, self-report screening tool to guide further assessment and intervention.

The Insomnia Severity Index (ISI) assess­es patients’ perceptions of their insomnia. The ISI was developed to aid both in the clinical evaluation of patients with insomnia and to measure treatment outcomes. Administration of the ISI takes approximately 5 minutes, and scoring takes less than 1 minute.

The ISI is composed of 7 items that mea­sure the severity of sleep onset and sleep main­tenance difficulties, satisfaction with current sleep, impact on daily functioning, impair­ment observable to others, and degree of dis­tress caused by the sleep problems. Each item is scored on a 0 to 4 Likert-type scale, and the individual items are summed for a total score of 0 to 28, with higher scores suggesting more severe insomnia. Evidence-based guidelines recommend cognitive behavioral therapy for insomnia (CBT-I) as the first-line treatment for adults with primary insomnia.¹⁹

Several validation studies have found the ISI to be a reliable measure of perceived in­somnia severity, and one that is sensitive to changes in patients’ perceptions of treatment outcomes.^20,21 An additional validation study confirmed that in primary care settings, a cut­off score of 14 should be used to indicate the likely presence of clinical insomnia²² and to guide further assessment and intervention.

The percentage of insomniac patients correctly identified with the ISI was 82.2%, with moderate sensitivity (82.4%) and speci­ficity (82.1%).²² A positive predictive value of 70% was found, meaning that an insomnia disorder is probable when the ISI total score is 14 or higher; conversely, the negative predic­tive value was 90.2%.

Continue to: Substance use and pain...

 

 

Substance use and pain

The evaluation of alcohol and drug use is an integral part of assessing risky health behav­iors. The 10-item Alcohol Use Disorder Iden­tification Test (AUDIT) is a self-report tool developed by the World Health Organiza­tion.^23,24 Validated in medical settings, scores of 8 or higher suggest problematic drinking.^25,26 The AUDIT has demonstrated high specificity (94%) and moderate sensitivity (81%) in pri­mary care settings.²⁷ The AUDIT-C (items 1, 2, and 3 of the AUDIT) has also demonstrated comparable sensitivity, although slightly low­er specificity, than the full AUDIT, suggesting that this 3-question screen can also be used in primary care settings.²⁷

Opioid medications, frequently pre­scribed for chronic pain, present serious risks for many patients. The Screener and Opioid Assessment for Patients with Pain–Revised (SOAPP-R) is a 24-item self-reporting scale that can be completed in approximately 10 minutes.²⁸ A score of 18 or higher has identified 81% of patients at high risk for opioid misuse in a clinical setting, with moderate specificity (68%). Although other factors should be considered when assess­ing risk of opioid misuse, the SOAPP-R is a helpful and quick addition to an opioid risk assessment.

The CRAFFT Screening Tool for Adoles­cent Substance Use is administered by the clinician for youths ages 14 to 21. The first 3 questions ask about use of alcohol, mari­juana, or other substances during the past 12 months. What follows are questions relat­ed to the young person’s specific experiences with substances in relation to Cars, Relaxation, being Alone, Forgetting, Family/Friends, and Trouble (CRAFFT). The CRAFFT has shown moderate sensitivity (76%) and good speci­ficity (94%) for identifying any problem with substance use.²⁹ These measures may be ad­ministered to clarify or confirm substance use patterns (ie, duration, frequency), or to determine the severity of problems re­lated to substance use (ie, social or legal problems).
 

Trauma and PTSD

Approximately 7.7 million adults per year will experience posttraumatic stress disor­der (PTSD) symptoms, although PTSD can affect individuals of any age.³⁰ Given the im­pact that trauma can have, assess for PTSD in patients who have a history of trauma or who otherwise seem to be at risk. The Post-traumatic Stress Disorder Checklist (PCL-5) is a 20-item self-report questionnaire that screens for symptoms directly from the Di­agnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) criteria for PTSD. One limitation is that the question­naire is only validated for adults ages 18 years or older. Completion of the PCL-5 takes 5 to 10 minutes. The PCL-5 has strong internal consistency reliability (94%) and test-retest reliability (82%).³¹ With a cutoff score of 33 or higher, the sensitivity and specificity have been shown to be moderately high (74.5% and 70.6%, respectively).³²

The Child and Adolescent Trauma Screen (CATS) is used to assess for poten­tially traumatic events and PTSD symptoms in children and adolescents. These symp­toms are based on the DSM-5, and there­fore the CATS can act as a useful diagnostic aid. The CATS is also available in Spanish, with both caregiver-report (for children ages 3-6 years or 7-17 years) and self-report (for ages 7-17 years) versions. Practical use of the PCL-5 and the CATS involves screen­ing for PTSD symptoms, supporting a pro­visional diagnosis of PTSD, and monitoring PTSD symptom changes during and after treatment.
 

Memory and cognition

Cognitive screening is a first step in evaluat­ing possible dementia and other neuropsy­chological disorders. The importance of brief cognitive screening in primary care cannot be understated, especially for an aging patient population. Although the Mini Mental Status Exam (MMSE) has been widely used among health care providers and researchers, we rec­ommend the Montreal Cognitive Assessment (MoCA).

The MoCA is a simple, standalone cogni­tive screening tool validated for adults ages 55 to 85 years.³³ The MoCA addresses many im­portant cognitive domains, fits on one page, and can be administered by a trained provider in 10 minutes. Research also suggests that it has strong test-retest reliability and positive and negative predictive values for mild cogni­tive impairment and Alzheimer dementia, and it has been found to be more sensitive than the MMSE.³⁴ We additionally recommend the MoCA as it measures several cognitive skills that are not addressed on the MMSE, includ­ing verbal fluency and abstraction.³⁴ Scores below 25 are suggestive of cognitive impair­ment and should lead to a referral for neuro­psychological testing.

The MoCA’s sensitivity for detecting cog­nitive impairment is high (94%), and specific­ity is low (42%).³⁵ To ensure consistency and accuracy in administering the MoCA, certifi­cation is now required via an online training program through www.mocatest.org.
 

Adapting these screening tools to practice

These tools are not meant to be used at every appointment. Every practice is different, and each clinic or physician can tailor the use of these screening tools to the needs of the patient population, as concerns arise, or in collaboration with other providers. Additionally, these screening tools can be used in both integrated care and in private practice, to prompt a more thorough assessment or to aid in—and inform—treatment. Although some physicians choose to administer certain screening tools at each clinic visit, knowing about the availability of other tools can be useful in assessing various issues. The FIGURE can be used to aid in the clini­cal decision-making process.

Many screening tools are available in the public domain to assess a variety of symptoms related to im­paired mental health. These tools can be used to quickly evaluate for mood, suicidal ide­ation or behavior, anxiety, sleep, substance use, pain, trauma, memory, and cognition (TABLE). Individuals with poor mental health incur high health care costs. Those suffering from anxiety and posttraumatic stress have more outpatient and emergency department visits and hospitalizations than patients with­out these disorders,^1,2 although use of mental health care services has been related to a de­crease in the overutilization of health care ser­vices in general.³

Here we review several screening tools that can help you to identify symptoms of mental illnesses and thus, provide prompt early intervention, including referrals to psy­chological and psychiatric services.

Mood disorders

Most patients with mood disorders are treated in primary care settings.⁴ Quickly measuring patients’ mood symptoms can expedite treat­ment for those who need it. Many primary care clinics use the 9-item Patient Health Question­naire (PHQ-9) to screen for depression.⁵ The US Preventive Services Task Force (USPSTF) has recommended screening for depression with adequate systems to ensure accurate diagnoses, effective treatment, and follow-up. Although the USPSTF did not specially endorse screening for bipolar disorder, it fol­lowed that recommendation with the qualify­ing statement, “positive screening results [for depression] should lead to additional assess­ment that considers severity of depression and comorbid psychological problems, alternate diagnoses, and medical conditions.”⁶ Thus, fol­lowing a positive screen result for depression, consider using a screening tool for mood dis­orders to provide diagnostic clarification.

The Mood Disorder Question­naire (MDQ) is a validated 15-item, self-administered questionnaire that takes only 5 minutes to use in screening adult patients for bipolar I disorder.⁷ The MDQ assesses specific behaviors related to bipolar disorder, symptom co-occurrence, and functional im­pairment. The MDQ has low sensitivity (58%) but good specificity (93%) in a primary care setting.⁸ However, the MDQ is not a diagnos­tic instrument. A positive screen result should prompt a more thorough clinical evaluation, if necessary, by a professional trained in psychi­atric disorders.

We recommend completing the MDQ pri­or to prescribing antidepressants. You can also monitor a patient’s response to treatment with serial MDQ testing. The MDQ is useful, too, when a patient has unclear mood symptoms that may have features overlapping with bi­polar disorder. Furthermore, we recommend screening for bipolar disorder with every patient who reports symptoms of depression, given that some pharmacologic treatments (predominately selective serotonin reuptake inhibitors) can induce mania in patients who actually have unrecognized bipolar disorder.⁹

Continue to: Suicide...

Suicide

Suicide is the 10th leading cause of death among the general population. All demo­graphic groups are impacted by suicide; how­ever, the most vulnerable are men ages 45 to 64 years.¹⁰ Given the imminent risk to indi­viduals who experience suicidal ideation, properly assessing and targeting suicidal risk is paramount.

The Columbia Suicide Severity Rating Scale (C-SSRS) can be completed in an inter­view format or as a patient self-report. Ver­sions of the C-SSRS are available for children, adolescents, and adults. It can be used in practice with any patient who may be at risk for suicide. Specifically, consider using the C-SSRS when a patient scores 1 or greater on the PHQ-9 or when risk is revealed with an­other brief screening tool that includes sui­cidal ideation.

The C-SSRS covers 10 categories related to suicidal ideation and behavior that the cli­nician explores with questions requiring only Yes/No responses. The C-SSRS demonstrates moderate-to-strong internal consistency and reliability, and it has shown a high degree of sensitivity (95%) and specificity (95%) for sui­cidal ideation.¹¹

Anxiety and physiologic arousal

Generalized anxiety disorder (GAD) is one of the most common anxiety disorders, with an estimated prevalence of 2.8% to 8.5% among primary care patients.¹² Brief, validated screening tools such as the Generalized Anxi­ety Disorder–7 item (GAD-7) scale can be ef­fective in identifying anxiety and other related disorders in primary care settings.

The GAD-7 comprises 7 items inquir­ing about symptoms experienced in the past 2 weeks. Scores range from 0 to 21, with cutoffs of 5, 10, and 15 indicating mild, moderate, and severe anxiety, respectively. This question­naire is appropriate for use with adults and has strong specificity, internal consistency, and test-retest reliability.¹² Specificity and sen­sitivity of the GAD-7 are maximized at a cutoff score of 10 or greater, both exceeding 80%.¹² The GAD-7 can be used when patients report symptoms of anxiety or when one needs to screen for anxiety with new patients or more clearly understand symptoms among patients who have complex mental health concerns.

The Screen for Child Anxiety Related Disorders (SCARED) is a 41-item self-report measure of anxiety for children ages 8 to 18. The SCARED questionnaire yields an overall anxiety score, as well as subscales for panic disorder or significant somatic symptoms, generalized anxiety disorder, separation anxi­ety, social anxiety disorder, and significant school avoidance.¹³ There is also a 5-item ver­sion of the SCARED, which can be useful for brief screening in fast-paced settings when no anxiety disorder is suspected, or for children who may have anxiety but exhibit reduced ver­bal capacity. The SCARED has been found to have moderate sensitivity (81.8%) and speci­ficity (52%) for diagnosing anxiety disorders in a community sample, with an optimal cutoff point of 22 on the total scale.¹⁴

Sleep

Sleep concerns are common, with the preva­lence of insomnia among adults in the United States estimated to be 19.2%.¹⁵ The importance of assessing these concerns cannot be over­stated, and primary care providers are the ones patients consult most often.¹⁶ The gold standard in assessing sleep disorders is a structured clinical interview, polysomnogra­phy, sleep diary, and actigraphy (home-based monitoring of movement through a device, often worn on the wrist).^17,18 However, this work-up is expensive, time-intensive, and im­practical in integrated care settings; thus the need for a brief, self-report screening tool to guide further assessment and intervention.

The Insomnia Severity Index (ISI) assess­es patients’ perceptions of their insomnia. The ISI was developed to aid both in the clinical evaluation of patients with insomnia and to measure treatment outcomes. Administration of the ISI takes approximately 5 minutes, and scoring takes less than 1 minute.

The ISI is composed of 7 items that mea­sure the severity of sleep onset and sleep main­tenance difficulties, satisfaction with current sleep, impact on daily functioning, impair­ment observable to others, and degree of dis­tress caused by the sleep problems. Each item is scored on a 0 to 4 Likert-type scale, and the individual items are summed for a total score of 0 to 28, with higher scores suggesting more severe insomnia. Evidence-based guidelines recommend cognitive behavioral therapy for insomnia (CBT-I) as the first-line treatment for adults with primary insomnia.¹⁹

Several validation studies have found the ISI to be a reliable measure of perceived in­somnia severity, and one that is sensitive to changes in patients’ perceptions of treatment outcomes.^20,21 An additional validation study confirmed that in primary care settings, a cut­off score of 14 should be used to indicate the likely presence of clinical insomnia²² and to guide further assessment and intervention.

The percentage of insomniac patients correctly identified with the ISI was 82.2%, with moderate sensitivity (82.4%) and speci­ficity (82.1%).²² A positive predictive value of 70% was found, meaning that an insomnia disorder is probable when the ISI total score is 14 or higher; conversely, the negative predic­tive value was 90.2%.

Continue to: Substance use and pain...

 

 

Substance use and pain

The evaluation of alcohol and drug use is an integral part of assessing risky health behav­iors. The 10-item Alcohol Use Disorder Iden­tification Test (AUDIT) is a self-report tool developed by the World Health Organiza­tion.^23,24 Validated in medical settings, scores of 8 or higher suggest problematic drinking.^25,26 The AUDIT has demonstrated high specificity (94%) and moderate sensitivity (81%) in pri­mary care settings.²⁷ The AUDIT-C (items 1, 2, and 3 of the AUDIT) has also demonstrated comparable sensitivity, although slightly low­er specificity, than the full AUDIT, suggesting that this 3-question screen can also be used in primary care settings.²⁷

Opioid medications, frequently pre­scribed for chronic pain, present serious risks for many patients. The Screener and Opioid Assessment for Patients with Pain–Revised (SOAPP-R) is a 24-item self-reporting scale that can be completed in approximately 10 minutes.²⁸ A score of 18 or higher has identified 81% of patients at high risk for opioid misuse in a clinical setting, with moderate specificity (68%). Although other factors should be considered when assess­ing risk of opioid misuse, the SOAPP-R is a helpful and quick addition to an opioid risk assessment.

The CRAFFT Screening Tool for Adoles­cent Substance Use is administered by the clinician for youths ages 14 to 21. The first 3 questions ask about use of alcohol, mari­juana, or other substances during the past 12 months. What follows are questions relat­ed to the young person’s specific experiences with substances in relation to Cars, Relaxation, being Alone, Forgetting, Family/Friends, and Trouble (CRAFFT). The CRAFFT has shown moderate sensitivity (76%) and good speci­ficity (94%) for identifying any problem with substance use.²⁹ These measures may be ad­ministered to clarify or confirm substance use patterns (ie, duration, frequency), or to determine the severity of problems re­lated to substance use (ie, social or legal problems).
 

Trauma and PTSD

Approximately 7.7 million adults per year will experience posttraumatic stress disor­der (PTSD) symptoms, although PTSD can affect individuals of any age.³⁰ Given the im­pact that trauma can have, assess for PTSD in patients who have a history of trauma or who otherwise seem to be at risk. The Post-traumatic Stress Disorder Checklist (PCL-5) is a 20-item self-report questionnaire that screens for symptoms directly from the Di­agnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) criteria for PTSD. One limitation is that the question­naire is only validated for adults ages 18 years or older. Completion of the PCL-5 takes 5 to 10 minutes. The PCL-5 has strong internal consistency reliability (94%) and test-retest reliability (82%).³¹ With a cutoff score of 33 or higher, the sensitivity and specificity have been shown to be moderately high (74.5% and 70.6%, respectively).³²

The Child and Adolescent Trauma Screen (CATS) is used to assess for poten­tially traumatic events and PTSD symptoms in children and adolescents. These symp­toms are based on the DSM-5, and there­fore the CATS can act as a useful diagnostic aid. The CATS is also available in Spanish, with both caregiver-report (for children ages 3-6 years or 7-17 years) and self-report (for ages 7-17 years) versions. Practical use of the PCL-5 and the CATS involves screen­ing for PTSD symptoms, supporting a pro­visional diagnosis of PTSD, and monitoring PTSD symptom changes during and after treatment.
 

Memory and cognition

Cognitive screening is a first step in evaluat­ing possible dementia and other neuropsy­chological disorders. The importance of brief cognitive screening in primary care cannot be understated, especially for an aging patient population. Although the Mini Mental Status Exam (MMSE) has been widely used among health care providers and researchers, we rec­ommend the Montreal Cognitive Assessment (MoCA).

The MoCA is a simple, standalone cogni­tive screening tool validated for adults ages 55 to 85 years.³³ The MoCA addresses many im­portant cognitive domains, fits on one page, and can be administered by a trained provider in 10 minutes. Research also suggests that it has strong test-retest reliability and positive and negative predictive values for mild cogni­tive impairment and Alzheimer dementia, and it has been found to be more sensitive than the MMSE.³⁴ We additionally recommend the MoCA as it measures several cognitive skills that are not addressed on the MMSE, includ­ing verbal fluency and abstraction.³⁴ Scores below 25 are suggestive of cognitive impair­ment and should lead to a referral for neuro­psychological testing.

The MoCA’s sensitivity for detecting cog­nitive impairment is high (94%), and specific­ity is low (42%).³⁵ To ensure consistency and accuracy in administering the MoCA, certifi­cation is now required via an online training program through www.mocatest.org.
 

Adapting these screening tools to practice

These tools are not meant to be used at every appointment. Every practice is different, and each clinic or physician can tailor the use of these screening tools to the needs of the patient population, as concerns arise, or in collaboration with other providers. Additionally, these screening tools can be used in both integrated care and in private practice, to prompt a more thorough assessment or to aid in—and inform—treatment. Although some physicians choose to administer certain screening tools at each clinic visit, knowing about the availability of other tools can be useful in assessing various issues. The FIGURE can be used to aid in the clini­cal decision-making process.

Many screening tools are available in the public domain to assess a variety of symptoms related to im­paired mental health. These tools can be used to quickly evaluate for mood, suicidal ide­ation or behavior, anxiety, sleep, substance use, pain, trauma, memory, and cognition (TABLE). Individuals with poor mental health incur high health care costs. Those suffering from anxiety and posttraumatic stress have more outpatient and emergency department visits and hospitalizations than patients with­out these disorders,^1,2 although use of mental health care services has been related to a de­crease in the overutilization of health care ser­vices in general.³

Here we review several screening tools that can help you to identify symptoms of mental illnesses and thus, provide prompt early intervention, including referrals to psy­chological and psychiatric services.

Mood disorders

Most patients with mood disorders are treated in primary care settings.⁴ Quickly measuring patients’ mood symptoms can expedite treat­ment for those who need it. Many primary care clinics use the 9-item Patient Health Question­naire (PHQ-9) to screen for depression.⁵ The US Preventive Services Task Force (USPSTF) has recommended screening for depression with adequate systems to ensure accurate diagnoses, effective treatment, and follow-up. Although the USPSTF did not specially endorse screening for bipolar disorder, it fol­lowed that recommendation with the qualify­ing statement, “positive screening results [for depression] should lead to additional assess­ment that considers severity of depression and comorbid psychological problems, alternate diagnoses, and medical conditions.”⁶ Thus, fol­lowing a positive screen result for depression, consider using a screening tool for mood dis­orders to provide diagnostic clarification.

The Mood Disorder Question­naire (MDQ) is a validated 15-item, self-administered questionnaire that takes only 5 minutes to use in screening adult patients for bipolar I disorder.⁷ The MDQ assesses specific behaviors related to bipolar disorder, symptom co-occurrence, and functional im­pairment. The MDQ has low sensitivity (58%) but good specificity (93%) in a primary care setting.⁸ However, the MDQ is not a diagnos­tic instrument. A positive screen result should prompt a more thorough clinical evaluation, if necessary, by a professional trained in psychi­atric disorders.

We recommend completing the MDQ pri­or to prescribing antidepressants. You can also monitor a patient’s response to treatment with serial MDQ testing. The MDQ is useful, too, when a patient has unclear mood symptoms that may have features overlapping with bi­polar disorder. Furthermore, we recommend screening for bipolar disorder with every patient who reports symptoms of depression, given that some pharmacologic treatments (predominately selective serotonin reuptake inhibitors) can induce mania in patients who actually have unrecognized bipolar disorder.⁹

Continue to: Suicide...

Suicide

Suicide is the 10th leading cause of death among the general population. All demo­graphic groups are impacted by suicide; how­ever, the most vulnerable are men ages 45 to 64 years.¹⁰ Given the imminent risk to indi­viduals who experience suicidal ideation, properly assessing and targeting suicidal risk is paramount.

The Columbia Suicide Severity Rating Scale (C-SSRS) can be completed in an inter­view format or as a patient self-report. Ver­sions of the C-SSRS are available for children, adolescents, and adults. It can be used in practice with any patient who may be at risk for suicide. Specifically, consider using the C-SSRS when a patient scores 1 or greater on the PHQ-9 or when risk is revealed with an­other brief screening tool that includes sui­cidal ideation.

The C-SSRS covers 10 categories related to suicidal ideation and behavior that the cli­nician explores with questions requiring only Yes/No responses. The C-SSRS demonstrates moderate-to-strong internal consistency and reliability, and it has shown a high degree of sensitivity (95%) and specificity (95%) for sui­cidal ideation.¹¹

Anxiety and physiologic arousal

Generalized anxiety disorder (GAD) is one of the most common anxiety disorders, with an estimated prevalence of 2.8% to 8.5% among primary care patients.¹² Brief, validated screening tools such as the Generalized Anxi­ety Disorder–7 item (GAD-7) scale can be ef­fective in identifying anxiety and other related disorders in primary care settings.

The GAD-7 comprises 7 items inquir­ing about symptoms experienced in the past 2 weeks. Scores range from 0 to 21, with cutoffs of 5, 10, and 15 indicating mild, moderate, and severe anxiety, respectively. This question­naire is appropriate for use with adults and has strong specificity, internal consistency, and test-retest reliability.¹² Specificity and sen­sitivity of the GAD-7 are maximized at a cutoff score of 10 or greater, both exceeding 80%.¹² The GAD-7 can be used when patients report symptoms of anxiety or when one needs to screen for anxiety with new patients or more clearly understand symptoms among patients who have complex mental health concerns.

The Screen for Child Anxiety Related Disorders (SCARED) is a 41-item self-report measure of anxiety for children ages 8 to 18. The SCARED questionnaire yields an overall anxiety score, as well as subscales for panic disorder or significant somatic symptoms, generalized anxiety disorder, separation anxi­ety, social anxiety disorder, and significant school avoidance.¹³ There is also a 5-item ver­sion of the SCARED, which can be useful for brief screening in fast-paced settings when no anxiety disorder is suspected, or for children who may have anxiety but exhibit reduced ver­bal capacity. The SCARED has been found to have moderate sensitivity (81.8%) and speci­ficity (52%) for diagnosing anxiety disorders in a community sample, with an optimal cutoff point of 22 on the total scale.¹⁴

Sleep

Sleep concerns are common, with the preva­lence of insomnia among adults in the United States estimated to be 19.2%.¹⁵ The importance of assessing these concerns cannot be over­stated, and primary care providers are the ones patients consult most often.¹⁶ The gold standard in assessing sleep disorders is a structured clinical interview, polysomnogra­phy, sleep diary, and actigraphy (home-based monitoring of movement through a device, often worn on the wrist).^17,18 However, this work-up is expensive, time-intensive, and im­practical in integrated care settings; thus the need for a brief, self-report screening tool to guide further assessment and intervention.

The Insomnia Severity Index (ISI) assess­es patients’ perceptions of their insomnia. The ISI was developed to aid both in the clinical evaluation of patients with insomnia and to measure treatment outcomes. Administration of the ISI takes approximately 5 minutes, and scoring takes less than 1 minute.

The ISI is composed of 7 items that mea­sure the severity of sleep onset and sleep main­tenance difficulties, satisfaction with current sleep, impact on daily functioning, impair­ment observable to others, and degree of dis­tress caused by the sleep problems. Each item is scored on a 0 to 4 Likert-type scale, and the individual items are summed for a total score of 0 to 28, with higher scores suggesting more severe insomnia. Evidence-based guidelines recommend cognitive behavioral therapy for insomnia (CBT-I) as the first-line treatment for adults with primary insomnia.¹⁹

Several validation studies have found the ISI to be a reliable measure of perceived in­somnia severity, and one that is sensitive to changes in patients’ perceptions of treatment outcomes.^20,21 An additional validation study confirmed that in primary care settings, a cut­off score of 14 should be used to indicate the likely presence of clinical insomnia²² and to guide further assessment and intervention.

The percentage of insomniac patients correctly identified with the ISI was 82.2%, with moderate sensitivity (82.4%) and speci­ficity (82.1%).²² A positive predictive value of 70% was found, meaning that an insomnia disorder is probable when the ISI total score is 14 or higher; conversely, the negative predic­tive value was 90.2%.

Continue to: Substance use and pain...

 

 

Substance use and pain

The evaluation of alcohol and drug use is an integral part of assessing risky health behav­iors. The 10-item Alcohol Use Disorder Iden­tification Test (AUDIT) is a self-report tool developed by the World Health Organiza­tion.^23,24 Validated in medical settings, scores of 8 or higher suggest problematic drinking.^25,26 The AUDIT has demonstrated high specificity (94%) and moderate sensitivity (81%) in pri­mary care settings.²⁷ The AUDIT-C (items 1, 2, and 3 of the AUDIT) has also demonstrated comparable sensitivity, although slightly low­er specificity, than the full AUDIT, suggesting that this 3-question screen can also be used in primary care settings.²⁷

Opioid medications, frequently pre­scribed for chronic pain, present serious risks for many patients. The Screener and Opioid Assessment for Patients with Pain–Revised (SOAPP-R) is a 24-item self-reporting scale that can be completed in approximately 10 minutes.²⁸ A score of 18 or higher has identified 81% of patients at high risk for opioid misuse in a clinical setting, with moderate specificity (68%). Although other factors should be considered when assess­ing risk of opioid misuse, the SOAPP-R is a helpful and quick addition to an opioid risk assessment.

The CRAFFT Screening Tool for Adoles­cent Substance Use is administered by the clinician for youths ages 14 to 21. The first 3 questions ask about use of alcohol, mari­juana, or other substances during the past 12 months. What follows are questions relat­ed to the young person’s specific experiences with substances in relation to Cars, Relaxation, being Alone, Forgetting, Family/Friends, and Trouble (CRAFFT). The CRAFFT has shown moderate sensitivity (76%) and good speci­ficity (94%) for identifying any problem with substance use.²⁹ These measures may be ad­ministered to clarify or confirm substance use patterns (ie, duration, frequency), or to determine the severity of problems re­lated to substance use (ie, social or legal problems).
 

Trauma and PTSD

Approximately 7.7 million adults per year will experience posttraumatic stress disor­der (PTSD) symptoms, although PTSD can affect individuals of any age.³⁰ Given the im­pact that trauma can have, assess for PTSD in patients who have a history of trauma or who otherwise seem to be at risk. The Post-traumatic Stress Disorder Checklist (PCL-5) is a 20-item self-report questionnaire that screens for symptoms directly from the Di­agnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) criteria for PTSD. One limitation is that the question­naire is only validated for adults ages 18 years or older. Completion of the PCL-5 takes 5 to 10 minutes. The PCL-5 has strong internal consistency reliability (94%) and test-retest reliability (82%).³¹ With a cutoff score of 33 or higher, the sensitivity and specificity have been shown to be moderately high (74.5% and 70.6%, respectively).³²

The Child and Adolescent Trauma Screen (CATS) is used to assess for poten­tially traumatic events and PTSD symptoms in children and adolescents. These symp­toms are based on the DSM-5, and there­fore the CATS can act as a useful diagnostic aid. The CATS is also available in Spanish, with both caregiver-report (for children ages 3-6 years or 7-17 years) and self-report (for ages 7-17 years) versions. Practical use of the PCL-5 and the CATS involves screen­ing for PTSD symptoms, supporting a pro­visional diagnosis of PTSD, and monitoring PTSD symptom changes during and after treatment.
 

Memory and cognition

Cognitive screening is a first step in evaluat­ing possible dementia and other neuropsy­chological disorders. The importance of brief cognitive screening in primary care cannot be understated, especially for an aging patient population. Although the Mini Mental Status Exam (MMSE) has been widely used among health care providers and researchers, we rec­ommend the Montreal Cognitive Assessment (MoCA).

The MoCA is a simple, standalone cogni­tive screening tool validated for adults ages 55 to 85 years.³³ The MoCA addresses many im­portant cognitive domains, fits on one page, and can be administered by a trained provider in 10 minutes. Research also suggests that it has strong test-retest reliability and positive and negative predictive values for mild cogni­tive impairment and Alzheimer dementia, and it has been found to be more sensitive than the MMSE.³⁴ We additionally recommend the MoCA as it measures several cognitive skills that are not addressed on the MMSE, includ­ing verbal fluency and abstraction.³⁴ Scores below 25 are suggestive of cognitive impair­ment and should lead to a referral for neuro­psychological testing.

The MoCA’s sensitivity for detecting cog­nitive impairment is high (94%), and specific­ity is low (42%).³⁵ To ensure consistency and accuracy in administering the MoCA, certifi­cation is now required via an online training program through www.mocatest.org.
 

Adapting these screening tools to practice

These tools are not meant to be used at every appointment. Every practice is different, and each clinic or physician can tailor the use of these screening tools to the needs of the patient population, as concerns arise, or in collaboration with other providers. Additionally, these screening tools can be used in both integrated care and in private practice, to prompt a more thorough assessment or to aid in—and inform—treatment. Although some physicians choose to administer certain screening tools at each clinic visit, knowing about the availability of other tools can be useful in assessing various issues. The FIGURE can be used to aid in the clini­cal decision-making process.

Women at risk of preterm birth who took daily low-dose aspirin did not have significantly lower rates of preterm birth than those who did not take aspirin, according to preliminary findings from a small randomized controlled trial. There was a trend toward lower rates, especially among those with the highest compliance, but the study was underpowered to detect a difference with statistical significance, said Anadeijda Landman, MD, of the Amsterdam University Medical Center. Dr. Landman presented the findings Jan. 28 at a meeting sponsored by the Society for Maternal-Fetal Medicine.

Preterm birth accounts for a third of all neonatal mortality, she told attendees. Among 15 million preterm births worldwide each year, 65% are spontaneous, indicating the need for effective preventive interventions. Dr. Landman reviewed several mechanisms by which aspirin may help reduce preterm birth via different pathways.

The researchers’ multicenter, placebo-controlled trial involved 8 tertiary care and 26 secondary care hospitals in the Netherlands between May 2016 and June 2019. Starting between 8 and 15 weeks’ gestation, women took either 80 mg of aspirin or a placebo daily until 36 weeks’ gestation or delivery. Women also received progesterone, cerclage, or pessary as indicated according to local protocols.

The study enrolled 406 women with singleton pregnancy and a history of preterm birth delivered between 22 and 37 weeks’ gestation. The final analysis, after exclusions for pregnancy termination, congenital anomalies, multiples pregnancy, or similar reasons, included 193 women in the intervention group and 194 in the placebo group. The women had similar baseline characteristics across both groups except a higher number of past mid-trimester fetal deaths in the aspirin group.

“It’s important to realize these women had multiple preterm births, as one of our inclusion criteria was previous spontaneous preterm birth later than 22 weeks’ gestation, so this particular group is very high risk for cervical insufficiency as a probable cause,” Dr. Landman told attendees.

Among women in the aspirin group, 21.2% delivered before 37 weeks, compared with 25.4% in the placebo group (P = .323). The rate of spontaneous birth was 20.1% in the aspirin group and 23.8% in the placebo group (P = .376). Though still not statistically significant, the difference between the groups was larger when the researchers limited their analysis to the 245 women with at least 80% compliance: 18.5% of women in the aspirin group had a preterm birth, compared with 24.8% of women in the placebo group (P = .238).

There were no significant differences between the groups in composite poor neonatal outcomes or in a range of prespecified newborn complications. The aspirin group did have two stillbirths, two mid-trimester fetal losses, and two extremely preterm newborns (at 24+2 weeks and 25+2 weeks). The placebo group had two mid-trimester fetal losses.

“These deaths are inherent to the study population, and it seems unlikely they are related to the use of aspirin,” Dr. Landman said. “Moreover other aspirin studies have not found an increased perinatal mortality rate, and some large studies indicated the neonatal mortality rate is even reduced.”

Although preterm birth only trended lower in the aspirin group, Dr. Landman said the researchers believe they cannot rule out an effect from aspirin.

“It’s also important to note that our study was underpowered as the recurrence risk of preterm birth in our study was lower than expected, so it’s possible a small treatment effect of aspirin could not be demonstrated in our study,” she said. “And, despite the proper randomization procedure, many more women in the aspirin group had a previous mid-trimester fetal loss. This indicates that the aspirin group might be more at risk for preterm birth than the placebo group, and this imbalance could also have diminished a small protective effect of aspirin.”

In response to an audience question, Dr. Landman acknowledged that more recent studies on aspirin have used 100- to 150-mg dosages, but that evidence was not as clear when their study began in 2015. She added that her research team does not advise changing clinical care currently and believes it is too soon to recommend aspirin to this population.

Tracy Manuck, MD, MS, an associate professor of ob.gyn. at the University of North Carolina in Chapel Hill, agreed that it is premature to begin prescribing aspirin for preterm birth prevention, but she noted that most of the patients she cares for clinically already meet criteria for aspirin based on their risk factors for preeclampsia.

“Additional research is needed in the form of a well-designed and large [randomized, controlled trial],” Dr Manuck, who moderated the session, said in an interview. “However, such a trial is becoming increasingly difficult to conduct because so many pregnant women qualify to receive aspirin for the prevention of preeclampsia due to their weight, medical comorbidities, or prior pregnancy history.”

She said she anticipates seeing patient-level data meta-analyses in the coming months as more data on aspirin for preterm birth prevention are published.

“Given that these data are supportive of the overall trends seen in prior publications, I do think that low-dose aspirin will eventually bear out as a helpful preventative measure to prevent recurrent preterm birth. Aspirin is low risk, readily available, and is inexpensive,” Dr. Manuck said. “I hope that meta-analysis data will provide additional information regarding the benefit of low-dose aspirin for prematurity prevention.”

The research was funded by the Dutch Organization for Health Care Research and the Dutch Consortium for Research in Women’s Health. Dr. Landman and Dr. Manuck had no disclosures.

Women at risk of preterm birth who took daily low-dose aspirin did not have significantly lower rates of preterm birth than those who did not take aspirin, according to preliminary findings from a small randomized controlled trial. There was a trend toward lower rates, especially among those with the highest compliance, but the study was underpowered to detect a difference with statistical significance, said Anadeijda Landman, MD, of the Amsterdam University Medical Center. Dr. Landman presented the findings Jan. 28 at a meeting sponsored by the Society for Maternal-Fetal Medicine.

Preterm birth accounts for a third of all neonatal mortality, she told attendees. Among 15 million preterm births worldwide each year, 65% are spontaneous, indicating the need for effective preventive interventions. Dr. Landman reviewed several mechanisms by which aspirin may help reduce preterm birth via different pathways.

The researchers’ multicenter, placebo-controlled trial involved 8 tertiary care and 26 secondary care hospitals in the Netherlands between May 2016 and June 2019. Starting between 8 and 15 weeks’ gestation, women took either 80 mg of aspirin or a placebo daily until 36 weeks’ gestation or delivery. Women also received progesterone, cerclage, or pessary as indicated according to local protocols.

The study enrolled 406 women with singleton pregnancy and a history of preterm birth delivered between 22 and 37 weeks’ gestation. The final analysis, after exclusions for pregnancy termination, congenital anomalies, multiples pregnancy, or similar reasons, included 193 women in the intervention group and 194 in the placebo group. The women had similar baseline characteristics across both groups except a higher number of past mid-trimester fetal deaths in the aspirin group.

“It’s important to realize these women had multiple preterm births, as one of our inclusion criteria was previous spontaneous preterm birth later than 22 weeks’ gestation, so this particular group is very high risk for cervical insufficiency as a probable cause,” Dr. Landman told attendees.

Among women in the aspirin group, 21.2% delivered before 37 weeks, compared with 25.4% in the placebo group (P = .323). The rate of spontaneous birth was 20.1% in the aspirin group and 23.8% in the placebo group (P = .376). Though still not statistically significant, the difference between the groups was larger when the researchers limited their analysis to the 245 women with at least 80% compliance: 18.5% of women in the aspirin group had a preterm birth, compared with 24.8% of women in the placebo group (P = .238).

There were no significant differences between the groups in composite poor neonatal outcomes or in a range of prespecified newborn complications. The aspirin group did have two stillbirths, two mid-trimester fetal losses, and two extremely preterm newborns (at 24+2 weeks and 25+2 weeks). The placebo group had two mid-trimester fetal losses.

“These deaths are inherent to the study population, and it seems unlikely they are related to the use of aspirin,” Dr. Landman said. “Moreover other aspirin studies have not found an increased perinatal mortality rate, and some large studies indicated the neonatal mortality rate is even reduced.”

Although preterm birth only trended lower in the aspirin group, Dr. Landman said the researchers believe they cannot rule out an effect from aspirin.

“It’s also important to note that our study was underpowered as the recurrence risk of preterm birth in our study was lower than expected, so it’s possible a small treatment effect of aspirin could not be demonstrated in our study,” she said. “And, despite the proper randomization procedure, many more women in the aspirin group had a previous mid-trimester fetal loss. This indicates that the aspirin group might be more at risk for preterm birth than the placebo group, and this imbalance could also have diminished a small protective effect of aspirin.”

In response to an audience question, Dr. Landman acknowledged that more recent studies on aspirin have used 100- to 150-mg dosages, but that evidence was not as clear when their study began in 2015. She added that her research team does not advise changing clinical care currently and believes it is too soon to recommend aspirin to this population.

Tracy Manuck, MD, MS, an associate professor of ob.gyn. at the University of North Carolina in Chapel Hill, agreed that it is premature to begin prescribing aspirin for preterm birth prevention, but she noted that most of the patients she cares for clinically already meet criteria for aspirin based on their risk factors for preeclampsia.

“Additional research is needed in the form of a well-designed and large [randomized, controlled trial],” Dr Manuck, who moderated the session, said in an interview. “However, such a trial is becoming increasingly difficult to conduct because so many pregnant women qualify to receive aspirin for the prevention of preeclampsia due to their weight, medical comorbidities, or prior pregnancy history.”

She said she anticipates seeing patient-level data meta-analyses in the coming months as more data on aspirin for preterm birth prevention are published.

“Given that these data are supportive of the overall trends seen in prior publications, I do think that low-dose aspirin will eventually bear out as a helpful preventative measure to prevent recurrent preterm birth. Aspirin is low risk, readily available, and is inexpensive,” Dr. Manuck said. “I hope that meta-analysis data will provide additional information regarding the benefit of low-dose aspirin for prematurity prevention.”

The research was funded by the Dutch Organization for Health Care Research and the Dutch Consortium for Research in Women’s Health. Dr. Landman and Dr. Manuck had no disclosures.

Women at risk of preterm birth who took daily low-dose aspirin did not have significantly lower rates of preterm birth than those who did not take aspirin, according to preliminary findings from a small randomized controlled trial. There was a trend toward lower rates, especially among those with the highest compliance, but the study was underpowered to detect a difference with statistical significance, said Anadeijda Landman, MD, of the Amsterdam University Medical Center. Dr. Landman presented the findings Jan. 28 at a meeting sponsored by the Society for Maternal-Fetal Medicine.

Preterm birth accounts for a third of all neonatal mortality, she told attendees. Among 15 million preterm births worldwide each year, 65% are spontaneous, indicating the need for effective preventive interventions. Dr. Landman reviewed several mechanisms by which aspirin may help reduce preterm birth via different pathways.

The researchers’ multicenter, placebo-controlled trial involved 8 tertiary care and 26 secondary care hospitals in the Netherlands between May 2016 and June 2019. Starting between 8 and 15 weeks’ gestation, women took either 80 mg of aspirin or a placebo daily until 36 weeks’ gestation or delivery. Women also received progesterone, cerclage, or pessary as indicated according to local protocols.

The study enrolled 406 women with singleton pregnancy and a history of preterm birth delivered between 22 and 37 weeks’ gestation. The final analysis, after exclusions for pregnancy termination, congenital anomalies, multiples pregnancy, or similar reasons, included 193 women in the intervention group and 194 in the placebo group. The women had similar baseline characteristics across both groups except a higher number of past mid-trimester fetal deaths in the aspirin group.

“It’s important to realize these women had multiple preterm births, as one of our inclusion criteria was previous spontaneous preterm birth later than 22 weeks’ gestation, so this particular group is very high risk for cervical insufficiency as a probable cause,” Dr. Landman told attendees.

Among women in the aspirin group, 21.2% delivered before 37 weeks, compared with 25.4% in the placebo group (P = .323). The rate of spontaneous birth was 20.1% in the aspirin group and 23.8% in the placebo group (P = .376). Though still not statistically significant, the difference between the groups was larger when the researchers limited their analysis to the 245 women with at least 80% compliance: 18.5% of women in the aspirin group had a preterm birth, compared with 24.8% of women in the placebo group (P = .238).

There were no significant differences between the groups in composite poor neonatal outcomes or in a range of prespecified newborn complications. The aspirin group did have two stillbirths, two mid-trimester fetal losses, and two extremely preterm newborns (at 24+2 weeks and 25+2 weeks). The placebo group had two mid-trimester fetal losses.

“These deaths are inherent to the study population, and it seems unlikely they are related to the use of aspirin,” Dr. Landman said. “Moreover other aspirin studies have not found an increased perinatal mortality rate, and some large studies indicated the neonatal mortality rate is even reduced.”

Although preterm birth only trended lower in the aspirin group, Dr. Landman said the researchers believe they cannot rule out an effect from aspirin.

“It’s also important to note that our study was underpowered as the recurrence risk of preterm birth in our study was lower than expected, so it’s possible a small treatment effect of aspirin could not be demonstrated in our study,” she said. “And, despite the proper randomization procedure, many more women in the aspirin group had a previous mid-trimester fetal loss. This indicates that the aspirin group might be more at risk for preterm birth than the placebo group, and this imbalance could also have diminished a small protective effect of aspirin.”

In response to an audience question, Dr. Landman acknowledged that more recent studies on aspirin have used 100- to 150-mg dosages, but that evidence was not as clear when their study began in 2015. She added that her research team does not advise changing clinical care currently and believes it is too soon to recommend aspirin to this population.

Tracy Manuck, MD, MS, an associate professor of ob.gyn. at the University of North Carolina in Chapel Hill, agreed that it is premature to begin prescribing aspirin for preterm birth prevention, but she noted that most of the patients she cares for clinically already meet criteria for aspirin based on their risk factors for preeclampsia.

“Additional research is needed in the form of a well-designed and large [randomized, controlled trial],” Dr Manuck, who moderated the session, said in an interview. “However, such a trial is becoming increasingly difficult to conduct because so many pregnant women qualify to receive aspirin for the prevention of preeclampsia due to their weight, medical comorbidities, or prior pregnancy history.”

She said she anticipates seeing patient-level data meta-analyses in the coming months as more data on aspirin for preterm birth prevention are published.

“Given that these data are supportive of the overall trends seen in prior publications, I do think that low-dose aspirin will eventually bear out as a helpful preventative measure to prevent recurrent preterm birth. Aspirin is low risk, readily available, and is inexpensive,” Dr. Manuck said. “I hope that meta-analysis data will provide additional information regarding the benefit of low-dose aspirin for prematurity prevention.”

The research was funded by the Dutch Organization for Health Care Research and the Dutch Consortium for Research in Women’s Health. Dr. Landman and Dr. Manuck had no disclosures.

When 42-year-old Danielle Simone Brand started having hormonal migraines, she first turned to cannabidiol (CBD) oil, eventually adding an occasional pull on a prefilled tetrahydrocannabinol (THC) vape for nighttime use. She was careful to avoid THC during work hours. A parenting and cannabis writer, Ms. Brand had more than a cursory background in cannabinoid medicine and had spent time at her local California dispensary discussing various cannabinoid components that might help alleviate her pain.

Anatoliy Sizov/Getty Images

A self-professed “do-it-yourselfer,” Ms. Brand continues to use cannabinoids for her monthly headaches, forgoing any other pain medication. “There are times for conventional medicine in partnership with your doctor, but when it comes to health and wellness, women should be empowered to make decisions and self-experiment,” she said in an interview.

Ms. Brand is not alone. Significant numbers of women are replacing or supplementing prescription medications with cannabinoids, often without consulting their primary care physician, ob.gyn., or other specialist. At times, women have tried to have these conversations, only to be met with silence or worse.

Take Linda Fuller, a 58-year-old yoga instructor from Long Island who says that she uses CBD and THC for chronic sacroiliac pain after a car accident and to alleviate stress-triggered eczema flares. “I’ve had doctors turn their backs on me; I’ve had nurse practitioners walk out on me in the middle of a sentence,” she said in an interview.

Ms. Fuller said her conversion to cannabinoid medicine is relatively new; she never used cannabis recreationally before her accident but now considers it a gift. She doesn’t keep aspirin in the house and refused pain medication immediately after she injured her back.

Diana Krach, a 34-year-old writer from Maryland, says she’s encountered roadblocks about her decision to use cannabinoids for endometriosis and for pain from Crohn’s disease. When she tried to discuss her CBD use with a gastroenterologist, he interrupted her: “Whatever pot you’re smoking isn’t going to work, you’re going on biologics.”

Ms. Krach had not been smoking anything but had turned to a CBD tincture for symptom relief after prescription pain medications failed to help.

Ms. Brand, Ms. Fuller, and Ms. Krach are the tip of the iceberg when it comes to women seeking symptom relief outside the medicine cabinet. A recent survey in the Journal of Women’s Health of almost 1,000 women show that 90% (most between the ages of 35 and 44) had used cannabis and would consider using it to treat gynecologic pain. Roughly 80% said they would consider using it for procedure-related pain or other conditions. Additionally, women have reported using cannabinoids for PTSD, sleep disturbances or insomnia, anxiety, and migraine headaches.

Observational survey data have likewise shown that 80% of women with advanced or recurrent gynecologic malignancies who were prescribed cannabis reported that it was equivalent or superior to other medications for relieving pain, neuropathy, nausea, insomnia, decreased appetite, and anxiety.

In another survey, almost half (45%) of women with gynecologic malignancies who used nonprescribed cannabis for the same symptoms reported that they had reduced their use of prescription narcotics after initiating use of cannabis.
 

The gray zone

There has been a surge in self-reported cannabis use among pregnant women in particular. The National Survey on Drug Use and Health findings for the periods 2002-2003 and 2016-2017 highlight increases in adjusted prevalence rates from 3.4% to 7% in past-month use among pregnant women overall and from 5.7% to 12.1% during the first trimester alone.

“The more that you talk to pregnant women, the more that you realize that a lot are using cannabinoids for something that is basically medicinal, for sleep, for anxiety, or for nausea,” Katrina Mark, MD, an ob.gyn. and associate professor of medicine at the University of Maryland, College Park, said in an interview. “I’m not saying it’s fine to use drugs in pregnancy, but it is a grayer conversation than a lot of colleagues want to believe. Telling women to quit seems foolish since the alternative is to be anxious, don’t sleep, don’t eat, or use a medication that also has risks to it.”

One observational study shows that pregnant women themselves are conflicted. Although the majority believe that cannabis is “natural” and “safe,” compared with prescription drugs, they aren’t entirely in the dark about potential risks. They often express frustration with practitioners’ responses when these topics are broached during office visits. An observational survey among women and practitioners published in 2020 highlights that only half of doctors openly discouraged perinatal cannabis use and that others opted out of the discussion entirely.

This is the experience of many of the women that this news organization spoke with. Ms. Krach pointed out that “there’s a big deficit in listening; the doctor is supposed to be working for our behalf, especially when it comes to reproductive health.”

Dr. Mark believed that a lot of the conversation has been clouded by the illegality of the substance but that cannabinoids deserve as much of a fair chance for discussion and consideration as other medicines, which also carry risks in pregnancy. “There’s literally no evidence that it will work in pregnancy [for these symptoms], but there’s no evidence that it doesn’t, either,” she said in an interview. “When I have this conversation with colleagues who do not share my views, I try to encourage them to look at the actual risks versus the benefits versus the alternatives.”

The ‘entourage effect’

Data supporting cannabinoids have been mostly laboratory based, case based, or observational. However, several well-designed (albeit small) trials have demonstrated efficacy for chronic pain conditions, including neuropathic and headache pain, as well as in Crohn’s disease. Most investigators have concluded that dosage is important and that there is a synergistic interaction between compounds (known as the “entourage effect”) that relates to cannabinoid efficacy or lack thereof, as well as possible adverse effects.

In addition to legality issues, the entourage effect is one of the most important factors related to the medical use of cannabinoids. “There are literally thousands of cultivars of cannabis, each with their own phytocannabinoid and terpenic profiles that may produce distinct therapeutic effects, [so] it is misguided to speak of cannabis in monolithic terms. It is like making broad claims about soup,” wrote coauthor Samoon Ahmad, MD, in Medical Marijuana: A Clinical Handbook.

Additionally, the role that reproductive hormones play is not entirely understood. Reproductive-aged women appear to be more susceptible to a “telescoping” (gender-related progression to dependence) effect in comparison with men. Ziva Cooper, PhD, director of the Cannabis Research Initiative at the University of California, Los Angeles, said in an interview. She explained that research has shown that factors such as the degree of exposure, frequency of use, and menses confound this susceptibility.
 

It’s the data

Frustration over cannabinoid therapeutics abound, especially when it comes to data, legal issues, and lack of training. “The feedback that I hear from providers is that there isn’t enough information; we just don’t know enough about it,” Dr. Mark said, “but there is information that we do have, and ignoring it is not beneficial.”

Dr. Cooper concurred. Although she readily acknowledges that data from randomized, placebo-controlled trials are mostly lacking, she says, “There are signals in the literature providing evidence for the utility of cannabis and cannabinoids for pain and some other effects.”

Other practitioners said in an interview that some patients admit to using cannabinoids but that they lack the ample information to guide these patients. By and large, many women equate “natural” with “safe,” and some will experiment on their own to see what works.

Those experiments are not without risk, which is why “it’s just as important for physicians to talk to their patients about cannabis use as it is for patients to be forthcoming about that use,” said Dr. Cooper. “It could have implications on their overall health as well as interactions with other drugs that they’re using.”

That balance from a clinical perspective on cannabis is crucial, wrote coauthor Kenneth Hill, MD, in Medical Marijuana: A Clinical Handbook. “Without it,” he wrote, “the window of opportunity for a patient to accept treatment that she needs may not be open very long.”

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

When 42-year-old Danielle Simone Brand started having hormonal migraines, she first turned to cannabidiol (CBD) oil, eventually adding an occasional pull on a prefilled tetrahydrocannabinol (THC) vape for nighttime use. She was careful to avoid THC during work hours. A parenting and cannabis writer, Ms. Brand had more than a cursory background in cannabinoid medicine and had spent time at her local California dispensary discussing various cannabinoid components that might help alleviate her pain.

Anatoliy Sizov/Getty Images

A self-professed “do-it-yourselfer,” Ms. Brand continues to use cannabinoids for her monthly headaches, forgoing any other pain medication. “There are times for conventional medicine in partnership with your doctor, but when it comes to health and wellness, women should be empowered to make decisions and self-experiment,” she said in an interview.

Ms. Brand is not alone. Significant numbers of women are replacing or supplementing prescription medications with cannabinoids, often without consulting their primary care physician, ob.gyn., or other specialist. At times, women have tried to have these conversations, only to be met with silence or worse.

Take Linda Fuller, a 58-year-old yoga instructor from Long Island who says that she uses CBD and THC for chronic sacroiliac pain after a car accident and to alleviate stress-triggered eczema flares. “I’ve had doctors turn their backs on me; I’ve had nurse practitioners walk out on me in the middle of a sentence,” she said in an interview.

Ms. Fuller said her conversion to cannabinoid medicine is relatively new; she never used cannabis recreationally before her accident but now considers it a gift. She doesn’t keep aspirin in the house and refused pain medication immediately after she injured her back.

Diana Krach, a 34-year-old writer from Maryland, says she’s encountered roadblocks about her decision to use cannabinoids for endometriosis and for pain from Crohn’s disease. When she tried to discuss her CBD use with a gastroenterologist, he interrupted her: “Whatever pot you’re smoking isn’t going to work, you’re going on biologics.”

Ms. Krach had not been smoking anything but had turned to a CBD tincture for symptom relief after prescription pain medications failed to help.

Ms. Brand, Ms. Fuller, and Ms. Krach are the tip of the iceberg when it comes to women seeking symptom relief outside the medicine cabinet. A recent survey in the Journal of Women’s Health of almost 1,000 women show that 90% (most between the ages of 35 and 44) had used cannabis and would consider using it to treat gynecologic pain. Roughly 80% said they would consider using it for procedure-related pain or other conditions. Additionally, women have reported using cannabinoids for PTSD, sleep disturbances or insomnia, anxiety, and migraine headaches.

Observational survey data have likewise shown that 80% of women with advanced or recurrent gynecologic malignancies who were prescribed cannabis reported that it was equivalent or superior to other medications for relieving pain, neuropathy, nausea, insomnia, decreased appetite, and anxiety.

In another survey, almost half (45%) of women with gynecologic malignancies who used nonprescribed cannabis for the same symptoms reported that they had reduced their use of prescription narcotics after initiating use of cannabis.
 

The gray zone

There has been a surge in self-reported cannabis use among pregnant women in particular. The National Survey on Drug Use and Health findings for the periods 2002-2003 and 2016-2017 highlight increases in adjusted prevalence rates from 3.4% to 7% in past-month use among pregnant women overall and from 5.7% to 12.1% during the first trimester alone.

“The more that you talk to pregnant women, the more that you realize that a lot are using cannabinoids for something that is basically medicinal, for sleep, for anxiety, or for nausea,” Katrina Mark, MD, an ob.gyn. and associate professor of medicine at the University of Maryland, College Park, said in an interview. “I’m not saying it’s fine to use drugs in pregnancy, but it is a grayer conversation than a lot of colleagues want to believe. Telling women to quit seems foolish since the alternative is to be anxious, don’t sleep, don’t eat, or use a medication that also has risks to it.”

One observational study shows that pregnant women themselves are conflicted. Although the majority believe that cannabis is “natural” and “safe,” compared with prescription drugs, they aren’t entirely in the dark about potential risks. They often express frustration with practitioners’ responses when these topics are broached during office visits. An observational survey among women and practitioners published in 2020 highlights that only half of doctors openly discouraged perinatal cannabis use and that others opted out of the discussion entirely.

This is the experience of many of the women that this news organization spoke with. Ms. Krach pointed out that “there’s a big deficit in listening; the doctor is supposed to be working for our behalf, especially when it comes to reproductive health.”

Dr. Mark believed that a lot of the conversation has been clouded by the illegality of the substance but that cannabinoids deserve as much of a fair chance for discussion and consideration as other medicines, which also carry risks in pregnancy. “There’s literally no evidence that it will work in pregnancy [for these symptoms], but there’s no evidence that it doesn’t, either,” she said in an interview. “When I have this conversation with colleagues who do not share my views, I try to encourage them to look at the actual risks versus the benefits versus the alternatives.”

The ‘entourage effect’

Data supporting cannabinoids have been mostly laboratory based, case based, or observational. However, several well-designed (albeit small) trials have demonstrated efficacy for chronic pain conditions, including neuropathic and headache pain, as well as in Crohn’s disease. Most investigators have concluded that dosage is important and that there is a synergistic interaction between compounds (known as the “entourage effect”) that relates to cannabinoid efficacy or lack thereof, as well as possible adverse effects.

In addition to legality issues, the entourage effect is one of the most important factors related to the medical use of cannabinoids. “There are literally thousands of cultivars of cannabis, each with their own phytocannabinoid and terpenic profiles that may produce distinct therapeutic effects, [so] it is misguided to speak of cannabis in monolithic terms. It is like making broad claims about soup,” wrote coauthor Samoon Ahmad, MD, in Medical Marijuana: A Clinical Handbook.

Additionally, the role that reproductive hormones play is not entirely understood. Reproductive-aged women appear to be more susceptible to a “telescoping” (gender-related progression to dependence) effect in comparison with men. Ziva Cooper, PhD, director of the Cannabis Research Initiative at the University of California, Los Angeles, said in an interview. She explained that research has shown that factors such as the degree of exposure, frequency of use, and menses confound this susceptibility.
 

It’s the data

Frustration over cannabinoid therapeutics abound, especially when it comes to data, legal issues, and lack of training. “The feedback that I hear from providers is that there isn’t enough information; we just don’t know enough about it,” Dr. Mark said, “but there is information that we do have, and ignoring it is not beneficial.”

Dr. Cooper concurred. Although she readily acknowledges that data from randomized, placebo-controlled trials are mostly lacking, she says, “There are signals in the literature providing evidence for the utility of cannabis and cannabinoids for pain and some other effects.”

Other practitioners said in an interview that some patients admit to using cannabinoids but that they lack the ample information to guide these patients. By and large, many women equate “natural” with “safe,” and some will experiment on their own to see what works.

Those experiments are not without risk, which is why “it’s just as important for physicians to talk to their patients about cannabis use as it is for patients to be forthcoming about that use,” said Dr. Cooper. “It could have implications on their overall health as well as interactions with other drugs that they’re using.”

That balance from a clinical perspective on cannabis is crucial, wrote coauthor Kenneth Hill, MD, in Medical Marijuana: A Clinical Handbook. “Without it,” he wrote, “the window of opportunity for a patient to accept treatment that she needs may not be open very long.”

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

When 42-year-old Danielle Simone Brand started having hormonal migraines, she first turned to cannabidiol (CBD) oil, eventually adding an occasional pull on a prefilled tetrahydrocannabinol (THC) vape for nighttime use. She was careful to avoid THC during work hours. A parenting and cannabis writer, Ms. Brand had more than a cursory background in cannabinoid medicine and had spent time at her local California dispensary discussing various cannabinoid components that might help alleviate her pain.

Anatoliy Sizov/Getty Images

A self-professed “do-it-yourselfer,” Ms. Brand continues to use cannabinoids for her monthly headaches, forgoing any other pain medication. “There are times for conventional medicine in partnership with your doctor, but when it comes to health and wellness, women should be empowered to make decisions and self-experiment,” she said in an interview.

Ms. Brand is not alone. Significant numbers of women are replacing or supplementing prescription medications with cannabinoids, often without consulting their primary care physician, ob.gyn., or other specialist. At times, women have tried to have these conversations, only to be met with silence or worse.

Take Linda Fuller, a 58-year-old yoga instructor from Long Island who says that she uses CBD and THC for chronic sacroiliac pain after a car accident and to alleviate stress-triggered eczema flares. “I’ve had doctors turn their backs on me; I’ve had nurse practitioners walk out on me in the middle of a sentence,” she said in an interview.

Ms. Fuller said her conversion to cannabinoid medicine is relatively new; she never used cannabis recreationally before her accident but now considers it a gift. She doesn’t keep aspirin in the house and refused pain medication immediately after she injured her back.

Diana Krach, a 34-year-old writer from Maryland, says she’s encountered roadblocks about her decision to use cannabinoids for endometriosis and for pain from Crohn’s disease. When she tried to discuss her CBD use with a gastroenterologist, he interrupted her: “Whatever pot you’re smoking isn’t going to work, you’re going on biologics.”

Ms. Krach had not been smoking anything but had turned to a CBD tincture for symptom relief after prescription pain medications failed to help.

Ms. Brand, Ms. Fuller, and Ms. Krach are the tip of the iceberg when it comes to women seeking symptom relief outside the medicine cabinet. A recent survey in the Journal of Women’s Health of almost 1,000 women show that 90% (most between the ages of 35 and 44) had used cannabis and would consider using it to treat gynecologic pain. Roughly 80% said they would consider using it for procedure-related pain or other conditions. Additionally, women have reported using cannabinoids for PTSD, sleep disturbances or insomnia, anxiety, and migraine headaches.

Observational survey data have likewise shown that 80% of women with advanced or recurrent gynecologic malignancies who were prescribed cannabis reported that it was equivalent or superior to other medications for relieving pain, neuropathy, nausea, insomnia, decreased appetite, and anxiety.

In another survey, almost half (45%) of women with gynecologic malignancies who used nonprescribed cannabis for the same symptoms reported that they had reduced their use of prescription narcotics after initiating use of cannabis.
 

The gray zone

There has been a surge in self-reported cannabis use among pregnant women in particular. The National Survey on Drug Use and Health findings for the periods 2002-2003 and 2016-2017 highlight increases in adjusted prevalence rates from 3.4% to 7% in past-month use among pregnant women overall and from 5.7% to 12.1% during the first trimester alone.

“The more that you talk to pregnant women, the more that you realize that a lot are using cannabinoids for something that is basically medicinal, for sleep, for anxiety, or for nausea,” Katrina Mark, MD, an ob.gyn. and associate professor of medicine at the University of Maryland, College Park, said in an interview. “I’m not saying it’s fine to use drugs in pregnancy, but it is a grayer conversation than a lot of colleagues want to believe. Telling women to quit seems foolish since the alternative is to be anxious, don’t sleep, don’t eat, or use a medication that also has risks to it.”

One observational study shows that pregnant women themselves are conflicted. Although the majority believe that cannabis is “natural” and “safe,” compared with prescription drugs, they aren’t entirely in the dark about potential risks. They often express frustration with practitioners’ responses when these topics are broached during office visits. An observational survey among women and practitioners published in 2020 highlights that only half of doctors openly discouraged perinatal cannabis use and that others opted out of the discussion entirely.

This is the experience of many of the women that this news organization spoke with. Ms. Krach pointed out that “there’s a big deficit in listening; the doctor is supposed to be working for our behalf, especially when it comes to reproductive health.”

Dr. Mark believed that a lot of the conversation has been clouded by the illegality of the substance but that cannabinoids deserve as much of a fair chance for discussion and consideration as other medicines, which also carry risks in pregnancy. “There’s literally no evidence that it will work in pregnancy [for these symptoms], but there’s no evidence that it doesn’t, either,” she said in an interview. “When I have this conversation with colleagues who do not share my views, I try to encourage them to look at the actual risks versus the benefits versus the alternatives.”

The ‘entourage effect’

Data supporting cannabinoids have been mostly laboratory based, case based, or observational. However, several well-designed (albeit small) trials have demonstrated efficacy for chronic pain conditions, including neuropathic and headache pain, as well as in Crohn’s disease. Most investigators have concluded that dosage is important and that there is a synergistic interaction between compounds (known as the “entourage effect”) that relates to cannabinoid efficacy or lack thereof, as well as possible adverse effects.

In addition to legality issues, the entourage effect is one of the most important factors related to the medical use of cannabinoids. “There are literally thousands of cultivars of cannabis, each with their own phytocannabinoid and terpenic profiles that may produce distinct therapeutic effects, [so] it is misguided to speak of cannabis in monolithic terms. It is like making broad claims about soup,” wrote coauthor Samoon Ahmad, MD, in Medical Marijuana: A Clinical Handbook.

Additionally, the role that reproductive hormones play is not entirely understood. Reproductive-aged women appear to be more susceptible to a “telescoping” (gender-related progression to dependence) effect in comparison with men. Ziva Cooper, PhD, director of the Cannabis Research Initiative at the University of California, Los Angeles, said in an interview. She explained that research has shown that factors such as the degree of exposure, frequency of use, and menses confound this susceptibility.
 

It’s the data

Frustration over cannabinoid therapeutics abound, especially when it comes to data, legal issues, and lack of training. “The feedback that I hear from providers is that there isn’t enough information; we just don’t know enough about it,” Dr. Mark said, “but there is information that we do have, and ignoring it is not beneficial.”

Dr. Cooper concurred. Although she readily acknowledges that data from randomized, placebo-controlled trials are mostly lacking, she says, “There are signals in the literature providing evidence for the utility of cannabis and cannabinoids for pain and some other effects.”

Other practitioners said in an interview that some patients admit to using cannabinoids but that they lack the ample information to guide these patients. By and large, many women equate “natural” with “safe,” and some will experiment on their own to see what works.

Those experiments are not without risk, which is why “it’s just as important for physicians to talk to their patients about cannabis use as it is for patients to be forthcoming about that use,” said Dr. Cooper. “It could have implications on their overall health as well as interactions with other drugs that they’re using.”

That balance from a clinical perspective on cannabis is crucial, wrote coauthor Kenneth Hill, MD, in Medical Marijuana: A Clinical Handbook. “Without it,” he wrote, “the window of opportunity for a patient to accept treatment that she needs may not be open very long.”

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

The SARS-CoV-2 variant first detected in the United Kingdom is rapidly becoming the dominant strain in several countries and is doubling every 10 days in the United States, according to new data.

The findings by Nicole L. Washington, PhD, associate director of research at the genomics company Helix, and colleagues were posted Feb. 7, 2021, on the preprint server medRxiv. The paper has not been peer-reviewed in a scientific journal.

The researchers also found that the transmission rate in the United States of the variant, labeled B.1.1.7, is 30%-40% higher than that of more common lineages.

While clinical outcomes initially were thought to be similar to those of other SARS-CoV-2 variants, early reports suggest that infection with the B.1.1.7 variant may increase death risk by about 30%. 

A coauthor of the current study, Kristian Andersen, PhD, told the New York Times , “Nothing in this paper is surprising, but people need to see it.”

Dr. Andersen, a virologist at the Scripps Research Institute in La Jolla, Calif., added that “we should probably prepare for this being the predominant lineage in most places in the United States by March.”

The study of the B.1.1.7 variant adds support for the Centers for Disease Control and Prevention prediction in January that it would dominate by March.

“Our study shows that the U.S. is on a similar trajectory as other countries where B.1.1.7 rapidly became the dominant SARS-CoV-2 variant, requiring immediate and decisive action to minimize COVID-19 morbidity and mortality,” the researchers wrote.

The authors pointed out that the B.1.1.7 variant became the dominant SARS-CoV-2 strain in the United Kingdom within a couple of months of its detection.

“Since then, the variant has been increasingly observed across many European countries, including Portugal and Ireland, which, like the U.K., observed devastating waves of COVID-19 after B.1.1.7 became dominant,” the authors wrote.
 

“Category 5” storm

The B.1.1.7 variant has likely been spreading between U.S. states since at least December, they wrote.

This news organization reported on Jan. 15 that, as of Jan. 13, the B.1.1.7 variant was seen in 76 cases across 12 U.S. states, according to an early release of the CDC’s Morbidity and Mortality Weekly Report. 

As of Feb. 7, there were 690 cases of the B.1.1.7 variant in the US in 33 states, according to the CDC.

Dr. Washington and colleagues examined more than 500,000 coronavirus test samples from cases across the United States that were tested at San Mateo, Calif.–based Helix facilities since July.

In the study, they found inconsistent prevalence of the variant across states. By the last week in January, the researchers estimated the proportion of B.1.1.7 in the U.S. population to be about 2.1% of all COVID-19 cases, though they found it made up about 2% of all COVID-19 cases in California and about 4.5% of cases in Florida. The authors acknowledged that their data is less robust outside of those two states.

Though that seems a relatively low frequency, “our estimates show that its growth rate is at least 35%-45% increased and doubling every week and a half,” the authors wrote.

“Because laboratories in the U.S. are only sequencing a small subset of SARS-CoV-2 samples, the true sequence diversity of SARS-CoV-2 in this country is still unknown,” they noted.

Michael Osterholm, PhD, MPH, director of the Center for Infectious Disease Research and Policy at the University of Minnesota, Minneapolis, said last week that the United States is facing a “Category 5” storm with the spread of the B.1.1.7 variant as well as the variants first identified in South Africa and Brazil.

“We are going to see something like we have not seen yet in this country,” Dr. Osterholm said recently on NBC’s Meet the Press.

Lead author Nicole L. Washington and many of the coauthors are employees of Helix. Other coauthors are employees of Illumina. Three coauthors own stock in ILMN. The work was funded by Illumina, Helix, the Innovative Genomics Institute, and the New Frontiers in Research Fund provided by the Canadian Institutes of Health Research.

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

The SARS-CoV-2 variant first detected in the United Kingdom is rapidly becoming the dominant strain in several countries and is doubling every 10 days in the United States, according to new data.

The findings by Nicole L. Washington, PhD, associate director of research at the genomics company Helix, and colleagues were posted Feb. 7, 2021, on the preprint server medRxiv. The paper has not been peer-reviewed in a scientific journal.

The researchers also found that the transmission rate in the United States of the variant, labeled B.1.1.7, is 30%-40% higher than that of more common lineages.

While clinical outcomes initially were thought to be similar to those of other SARS-CoV-2 variants, early reports suggest that infection with the B.1.1.7 variant may increase death risk by about 30%. 

A coauthor of the current study, Kristian Andersen, PhD, told the New York Times , “Nothing in this paper is surprising, but people need to see it.”

Dr. Andersen, a virologist at the Scripps Research Institute in La Jolla, Calif., added that “we should probably prepare for this being the predominant lineage in most places in the United States by March.”

The study of the B.1.1.7 variant adds support for the Centers for Disease Control and Prevention prediction in January that it would dominate by March.

“Our study shows that the U.S. is on a similar trajectory as other countries where B.1.1.7 rapidly became the dominant SARS-CoV-2 variant, requiring immediate and decisive action to minimize COVID-19 morbidity and mortality,” the researchers wrote.

The authors pointed out that the B.1.1.7 variant became the dominant SARS-CoV-2 strain in the United Kingdom within a couple of months of its detection.

“Since then, the variant has been increasingly observed across many European countries, including Portugal and Ireland, which, like the U.K., observed devastating waves of COVID-19 after B.1.1.7 became dominant,” the authors wrote.
 

“Category 5” storm

The B.1.1.7 variant has likely been spreading between U.S. states since at least December, they wrote.

This news organization reported on Jan. 15 that, as of Jan. 13, the B.1.1.7 variant was seen in 76 cases across 12 U.S. states, according to an early release of the CDC’s Morbidity and Mortality Weekly Report. 

As of Feb. 7, there were 690 cases of the B.1.1.7 variant in the US in 33 states, according to the CDC.

Dr. Washington and colleagues examined more than 500,000 coronavirus test samples from cases across the United States that were tested at San Mateo, Calif.–based Helix facilities since July.

In the study, they found inconsistent prevalence of the variant across states. By the last week in January, the researchers estimated the proportion of B.1.1.7 in the U.S. population to be about 2.1% of all COVID-19 cases, though they found it made up about 2% of all COVID-19 cases in California and about 4.5% of cases in Florida. The authors acknowledged that their data is less robust outside of those two states.

Though that seems a relatively low frequency, “our estimates show that its growth rate is at least 35%-45% increased and doubling every week and a half,” the authors wrote.

“Because laboratories in the U.S. are only sequencing a small subset of SARS-CoV-2 samples, the true sequence diversity of SARS-CoV-2 in this country is still unknown,” they noted.

Michael Osterholm, PhD, MPH, director of the Center for Infectious Disease Research and Policy at the University of Minnesota, Minneapolis, said last week that the United States is facing a “Category 5” storm with the spread of the B.1.1.7 variant as well as the variants first identified in South Africa and Brazil.

“We are going to see something like we have not seen yet in this country,” Dr. Osterholm said recently on NBC’s Meet the Press.

Lead author Nicole L. Washington and many of the coauthors are employees of Helix. Other coauthors are employees of Illumina. Three coauthors own stock in ILMN. The work was funded by Illumina, Helix, the Innovative Genomics Institute, and the New Frontiers in Research Fund provided by the Canadian Institutes of Health Research.

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

The SARS-CoV-2 variant first detected in the United Kingdom is rapidly becoming the dominant strain in several countries and is doubling every 10 days in the United States, according to new data.

The findings by Nicole L. Washington, PhD, associate director of research at the genomics company Helix, and colleagues were posted Feb. 7, 2021, on the preprint server medRxiv. The paper has not been peer-reviewed in a scientific journal.

The researchers also found that the transmission rate in the United States of the variant, labeled B.1.1.7, is 30%-40% higher than that of more common lineages.

While clinical outcomes initially were thought to be similar to those of other SARS-CoV-2 variants, early reports suggest that infection with the B.1.1.7 variant may increase death risk by about 30%. 

A coauthor of the current study, Kristian Andersen, PhD, told the New York Times , “Nothing in this paper is surprising, but people need to see it.”

Dr. Andersen, a virologist at the Scripps Research Institute in La Jolla, Calif., added that “we should probably prepare for this being the predominant lineage in most places in the United States by March.”

The study of the B.1.1.7 variant adds support for the Centers for Disease Control and Prevention prediction in January that it would dominate by March.

“Our study shows that the U.S. is on a similar trajectory as other countries where B.1.1.7 rapidly became the dominant SARS-CoV-2 variant, requiring immediate and decisive action to minimize COVID-19 morbidity and mortality,” the researchers wrote.

The authors pointed out that the B.1.1.7 variant became the dominant SARS-CoV-2 strain in the United Kingdom within a couple of months of its detection.

“Since then, the variant has been increasingly observed across many European countries, including Portugal and Ireland, which, like the U.K., observed devastating waves of COVID-19 after B.1.1.7 became dominant,” the authors wrote.
 

“Category 5” storm

The B.1.1.7 variant has likely been spreading between U.S. states since at least December, they wrote.

This news organization reported on Jan. 15 that, as of Jan. 13, the B.1.1.7 variant was seen in 76 cases across 12 U.S. states, according to an early release of the CDC’s Morbidity and Mortality Weekly Report. 

As of Feb. 7, there were 690 cases of the B.1.1.7 variant in the US in 33 states, according to the CDC.

Dr. Washington and colleagues examined more than 500,000 coronavirus test samples from cases across the United States that were tested at San Mateo, Calif.–based Helix facilities since July.

In the study, they found inconsistent prevalence of the variant across states. By the last week in January, the researchers estimated the proportion of B.1.1.7 in the U.S. population to be about 2.1% of all COVID-19 cases, though they found it made up about 2% of all COVID-19 cases in California and about 4.5% of cases in Florida. The authors acknowledged that their data is less robust outside of those two states.

Though that seems a relatively low frequency, “our estimates show that its growth rate is at least 35%-45% increased and doubling every week and a half,” the authors wrote.

“Because laboratories in the U.S. are only sequencing a small subset of SARS-CoV-2 samples, the true sequence diversity of SARS-CoV-2 in this country is still unknown,” they noted.

Michael Osterholm, PhD, MPH, director of the Center for Infectious Disease Research and Policy at the University of Minnesota, Minneapolis, said last week that the United States is facing a “Category 5” storm with the spread of the B.1.1.7 variant as well as the variants first identified in South Africa and Brazil.

“We are going to see something like we have not seen yet in this country,” Dr. Osterholm said recently on NBC’s Meet the Press.

Lead author Nicole L. Washington and many of the coauthors are employees of Helix. Other coauthors are employees of Illumina. Three coauthors own stock in ILMN. The work was funded by Illumina, Helix, the Innovative Genomics Institute, and the New Frontiers in Research Fund provided by the Canadian Institutes of Health Research.

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

States that implemented mask mandates in 2020 saw a decline in the growth of COVID-19 hospitalizations between March and October 2020, according to a new study published Feb. 5 in the CDC’s Morbidity and Mortality Weekly Report.

Hospitalization growth rates declined by 5.5 percentage points for adults between ages 18-64 about 3 weeks after the mandates were implemented, compared with climbing growth rates in the 4 weeks before mandates.

CDC Director Rochelle Walensky said she was pleased to see the results, but that it’s “too early” to tell whether President Joe Biden’s recent mask orders have had an effect on cases and hospitalizations in 2021.

“We’re going to be watching the mask data very carefully,” she said during a news briefing with the White House COVID-19 Response Team on Feb. 5. “I think it’s probably still a bit too early to tell, but I’m encouraged with the decrease in case rates right now.”

In another study published Feb. 5 in the Morbidity and Mortality Weekly Report, trained observers tracked mask use at six universities with mask mandates between September and November 2020. Overall, observers reported that about 92% of people wore masks correctly indoors, which varied based on the type of mask.

About 97% of people used N95 masks correctly, compared with 92% who used cloth masks, and 79% who used bandanas, scarves, or neck gaiters. Cloth masks were most common, and bandanas and scarves were least common.

The Biden administration is considering whether to send masks directly to American households to encourage people to wear them, according to NBC News. The White House COVID-19 Response Team is debating the logistics of mailing out masks, including how many to send and what the mask material would be, the news outlet reported.

Wisconsin Gov. Tony Evers reissued a new statewide mask mandate on Feb. 4, just an hour after the Republican-controlled legislature voted to repeal his previous mandate, according to The Associated Press. Gov. Evers said his priority is to keep people safe and that wearing a mask is the easiest way to do so.

“If the legislature keeps playing politics and we don’t keep wearing masks, we’re going to see more preventable deaths,” he said. “It’s going to take even longer to get our state and our economy back on track.”

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

States that implemented mask mandates in 2020 saw a decline in the growth of COVID-19 hospitalizations between March and October 2020, according to a new study published Feb. 5 in the CDC’s Morbidity and Mortality Weekly Report.

Hospitalization growth rates declined by 5.5 percentage points for adults between ages 18-64 about 3 weeks after the mandates were implemented, compared with climbing growth rates in the 4 weeks before mandates.

CDC Director Rochelle Walensky said she was pleased to see the results, but that it’s “too early” to tell whether President Joe Biden’s recent mask orders have had an effect on cases and hospitalizations in 2021.

“We’re going to be watching the mask data very carefully,” she said during a news briefing with the White House COVID-19 Response Team on Feb. 5. “I think it’s probably still a bit too early to tell, but I’m encouraged with the decrease in case rates right now.”

In another study published Feb. 5 in the Morbidity and Mortality Weekly Report, trained observers tracked mask use at six universities with mask mandates between September and November 2020. Overall, observers reported that about 92% of people wore masks correctly indoors, which varied based on the type of mask.

About 97% of people used N95 masks correctly, compared with 92% who used cloth masks, and 79% who used bandanas, scarves, or neck gaiters. Cloth masks were most common, and bandanas and scarves were least common.

The Biden administration is considering whether to send masks directly to American households to encourage people to wear them, according to NBC News. The White House COVID-19 Response Team is debating the logistics of mailing out masks, including how many to send and what the mask material would be, the news outlet reported.

Wisconsin Gov. Tony Evers reissued a new statewide mask mandate on Feb. 4, just an hour after the Republican-controlled legislature voted to repeal his previous mandate, according to The Associated Press. Gov. Evers said his priority is to keep people safe and that wearing a mask is the easiest way to do so.

“If the legislature keeps playing politics and we don’t keep wearing masks, we’re going to see more preventable deaths,” he said. “It’s going to take even longer to get our state and our economy back on track.”

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

States that implemented mask mandates in 2020 saw a decline in the growth of COVID-19 hospitalizations between March and October 2020, according to a new study published Feb. 5 in the CDC’s Morbidity and Mortality Weekly Report.

Hospitalization growth rates declined by 5.5 percentage points for adults between ages 18-64 about 3 weeks after the mandates were implemented, compared with climbing growth rates in the 4 weeks before mandates.

CDC Director Rochelle Walensky said she was pleased to see the results, but that it’s “too early” to tell whether President Joe Biden’s recent mask orders have had an effect on cases and hospitalizations in 2021.

“We’re going to be watching the mask data very carefully,” she said during a news briefing with the White House COVID-19 Response Team on Feb. 5. “I think it’s probably still a bit too early to tell, but I’m encouraged with the decrease in case rates right now.”

In another study published Feb. 5 in the Morbidity and Mortality Weekly Report, trained observers tracked mask use at six universities with mask mandates between September and November 2020. Overall, observers reported that about 92% of people wore masks correctly indoors, which varied based on the type of mask.

About 97% of people used N95 masks correctly, compared with 92% who used cloth masks, and 79% who used bandanas, scarves, or neck gaiters. Cloth masks were most common, and bandanas and scarves were least common.

The Biden administration is considering whether to send masks directly to American households to encourage people to wear them, according to NBC News. The White House COVID-19 Response Team is debating the logistics of mailing out masks, including how many to send and what the mask material would be, the news outlet reported.

Wisconsin Gov. Tony Evers reissued a new statewide mask mandate on Feb. 4, just an hour after the Republican-controlled legislature voted to repeal his previous mandate, according to The Associated Press. Gov. Evers said his priority is to keep people safe and that wearing a mask is the easiest way to do so.

“If the legislature keeps playing politics and we don’t keep wearing masks, we’re going to see more preventable deaths,” he said. “It’s going to take even longer to get our state and our economy back on track.”

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

New details confirm an increased risk of developing intracranial meningiomas after prolonged use of the hormonal product cyproterone acetate.

Cyproterone acetate is a synthetic progestogen and potent antiandrogen that has been used in the treatment of hirsutism, alopecia, early puberty, amenorrhea, acne, and prostate cancer, and has also been combined with an estrogen in hormone replacement therapy.

The new findings were published online in the BMJ. The primary analysis showed that, among women using cyproterone acetate, the rate of meningiomas was 23.8 per 100,000 person years vs. 4.5 per 100,000 in the control group. After adjusting for confounders, cyproterone acetate was associated with a sevenfold increased risk of meningioma.

These were young women – the mean age of participants was 29.4 years, and more than 40% of the cohort were younger than 25 years. The initial prescriber was a gynecologist for more than half (56.7%) of the participants, and 31.6% of prescriptions could correspond to the treatment of acne without hirsutism; 13.1% of prescriptions were compatible with management of hirsutism.

“Our study provides confirmation of the risk but also the measurement of the dose-effect relationship, the decrease in the risk after stopping use, and the preferential anatomical localization of meningiomas,” said lead author Alain Weill, MD, EPI-PHARE Scientific Interest Group, Saint-Denis, France.

“A large proportion of meningiomas involve the skull base, which is of considerable importance because skull base meningioma surgery is one of the most challenging forms of surgery and is associated with a much higher risk than surgery for convexity meningiomas,” he said in an interview.

Cyproterone acetate products have been available in Europe since the 1970s under various trade names and dose strengths (1, 2, 10, 50, and 100 mg), and marketed for various indications. These products are also marketed in many other industrialized nations, but not in the United States or Japan.

The link between cyproterone acetate and an increased risk of meningioma has been known for the past decade, and information on the risk of meningioma is already included in the prescribing information for cyproterone products.

Last year, the European Medicines Agency strengthened the warnings that were already in place and recommended that cyproterone products with daily doses of 10 mg or more be restricted because of the risk of developing meningioma.

“The recommendation from the EMA is a direct consequence of our study, that was sent to the EMA in summary form in 2018 and followed up with a very detailed with a report in summer 2019,” said Dr. Weill. “In light of this report, the European Medicines Agency recommended in February 2020 that drugs containing 10 mg or more of cyproterone acetate should only be used for hirsutism, androgenic alopecia, and acne and seborrhea once other treatment options have failed, including treatment with lower doses.”

Dr. Weill pointed out that two other epidemiologic studies have assessed the link between cyproterone acetate use and meningioma and showed an association. “Those studies and our own study are complementary and provide a coherent set of epidemiological evidence,” he said in the interview. “They show a documented risk for high-dose cyproterone acetate in men, women, and transgender people, and the absence of any observed risk for low-dose cyproterone acetate use in women.”
 

Strong dose-effect relationship

For their study, Dr. Weill and colleagues used data from the French administrative health care database. Between 2007 and 2014, 253,777 girls and women aged 7-70 years had begun using cyproterone acetate during that time period.

All participants had received at least one prescription for high-dose cyproterone acetate and did not have a history of meningioma, benign brain tumors, or long-term disease. They were considered to be exposed if they had received a cumulative dose of at least 3 g during the first 6 months (139,222 participants) and very slightly exposed (control group) when they had received a cumulative dose of less than 3 g (114,555 participants).

Overall, a total of 69 meningiomas were diagnosed in the exposed group (during 289,544 person years of follow-up) and 20 meningiomas in the control group (during 439,949 person years of follow-up). All were treated by surgery or radiotherapy.

When the analysis was done according to the cumulative dose, it showed a dose-effect relation, with a higher risk associated with a higher cumulative dose. The hazard ratio was not significant for exposure to less than 12 g of cyproterone acetate, but it jumped rapidly jumped as the dose climbed: The hazard ratio was 11.3 for 36-60 g and was 21.7 for 60 g or higher.

In a secondary analysis, the authors looked at the cohort who were already using cyproterone acetate in 2006 (n = 123,997). Women with long-term exposure were also taking estrogens more often (55.5% vs. 31.9%), and the incidence of meningioma in the exposed group was 141 per 100,000 person years, which was a risk greater than 20-fold (adjusted hazard ratio 21.2.) They also observed a strong dose-effect relationship, with adjusted hazard ratio ranging from 5.0 to 31.1.

However, the risk of meningioma decreased noticeably after treatment was stopped. At 1 year after discontinuing treatment, the risk of meningioma in the exposed group was 1.8-fold higher (1.0 to 3.2) than in the control group.

Dr. Weill noted the clinical implications of these findings: clinicians need to inform patients who have used high-dose cyproterone acetate for at least 3-5 years about the increased risk of intracranial meningioma, he said.  

“The indication of cyproterone acetate should be clearly defined and the lowest possible daily dose used,” he said. “In the context of prolonged use of high-dose cyproterone acetate, magnetic resonance imaging screening for meningioma should be considered.”

“In patients with a documented meningioma, cyproterone acetate should be discontinued because the meningioma might regress in response to treatment discontinuation and invasive treatment could be avoided,” Dr. Weill added.
 

Use only when necessary

Weighing in on the research, Adilia Hormigo, MD, PhD, director of neuro-oncology at The Tisch Cancer Institute at Mount Sinai Health System in New York, noted that, “it is well known that there are sex differences in the incidence of meningiomas, as they are more frequent in women than men, and there is an association between breast cancer and the occurrence of meningiomas.”

Progesterone and androgen receptors have been found in meningiomas, she said in an interview, and there is no consensus regarding estrogen receptors. “In addition, hormonal therapy to inhibit estrogen or progesterone receptors has not produced any decrease in meningiomas’ growth,” she said.

The current study revealed an association between prolonged use of cyproterone acetate with an increased incidence of meningiomas, and the sphenoid-orbital meningioma location was specific for the drug use. “It is unclear from the study if all the meningiomas were benign,” she said. “Even if they are benign, they can cause severe morbidity, including seizures.”

Dr. Hormigo recommended that an MRI be performed on any patient who is taking a long course of cyproterone acetate in order to evaluate the development of meningiomas or meningioma progression. “And the drug should only be used when necessary,” she added.

This research was funded by the French National Health Insurance Fund and the Health Product Epidemiology Scientific Interest Group. Dr. Weill is an employee of the French National Health Insurance Fund, as are several other coauthors. The other authors have disclosed no relevant financial relationships. Dr. Hormigo has disclosed no relevant financial relationships.

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

New details confirm an increased risk of developing intracranial meningiomas after prolonged use of the hormonal product cyproterone acetate.

Cyproterone acetate is a synthetic progestogen and potent antiandrogen that has been used in the treatment of hirsutism, alopecia, early puberty, amenorrhea, acne, and prostate cancer, and has also been combined with an estrogen in hormone replacement therapy.

The new findings were published online in the BMJ. The primary analysis showed that, among women using cyproterone acetate, the rate of meningiomas was 23.8 per 100,000 person years vs. 4.5 per 100,000 in the control group. After adjusting for confounders, cyproterone acetate was associated with a sevenfold increased risk of meningioma.

These were young women – the mean age of participants was 29.4 years, and more than 40% of the cohort were younger than 25 years. The initial prescriber was a gynecologist for more than half (56.7%) of the participants, and 31.6% of prescriptions could correspond to the treatment of acne without hirsutism; 13.1% of prescriptions were compatible with management of hirsutism.

“Our study provides confirmation of the risk but also the measurement of the dose-effect relationship, the decrease in the risk after stopping use, and the preferential anatomical localization of meningiomas,” said lead author Alain Weill, MD, EPI-PHARE Scientific Interest Group, Saint-Denis, France.

“A large proportion of meningiomas involve the skull base, which is of considerable importance because skull base meningioma surgery is one of the most challenging forms of surgery and is associated with a much higher risk than surgery for convexity meningiomas,” he said in an interview.

Cyproterone acetate products have been available in Europe since the 1970s under various trade names and dose strengths (1, 2, 10, 50, and 100 mg), and marketed for various indications. These products are also marketed in many other industrialized nations, but not in the United States or Japan.

The link between cyproterone acetate and an increased risk of meningioma has been known for the past decade, and information on the risk of meningioma is already included in the prescribing information for cyproterone products.

Last year, the European Medicines Agency strengthened the warnings that were already in place and recommended that cyproterone products with daily doses of 10 mg or more be restricted because of the risk of developing meningioma.

“The recommendation from the EMA is a direct consequence of our study, that was sent to the EMA in summary form in 2018 and followed up with a very detailed with a report in summer 2019,” said Dr. Weill. “In light of this report, the European Medicines Agency recommended in February 2020 that drugs containing 10 mg or more of cyproterone acetate should only be used for hirsutism, androgenic alopecia, and acne and seborrhea once other treatment options have failed, including treatment with lower doses.”

Dr. Weill pointed out that two other epidemiologic studies have assessed the link between cyproterone acetate use and meningioma and showed an association. “Those studies and our own study are complementary and provide a coherent set of epidemiological evidence,” he said in the interview. “They show a documented risk for high-dose cyproterone acetate in men, women, and transgender people, and the absence of any observed risk for low-dose cyproterone acetate use in women.”
 

Strong dose-effect relationship

For their study, Dr. Weill and colleagues used data from the French administrative health care database. Between 2007 and 2014, 253,777 girls and women aged 7-70 years had begun using cyproterone acetate during that time period.

All participants had received at least one prescription for high-dose cyproterone acetate and did not have a history of meningioma, benign brain tumors, or long-term disease. They were considered to be exposed if they had received a cumulative dose of at least 3 g during the first 6 months (139,222 participants) and very slightly exposed (control group) when they had received a cumulative dose of less than 3 g (114,555 participants).

Overall, a total of 69 meningiomas were diagnosed in the exposed group (during 289,544 person years of follow-up) and 20 meningiomas in the control group (during 439,949 person years of follow-up). All were treated by surgery or radiotherapy.

When the analysis was done according to the cumulative dose, it showed a dose-effect relation, with a higher risk associated with a higher cumulative dose. The hazard ratio was not significant for exposure to less than 12 g of cyproterone acetate, but it jumped rapidly jumped as the dose climbed: The hazard ratio was 11.3 for 36-60 g and was 21.7 for 60 g or higher.

In a secondary analysis, the authors looked at the cohort who were already using cyproterone acetate in 2006 (n = 123,997). Women with long-term exposure were also taking estrogens more often (55.5% vs. 31.9%), and the incidence of meningioma in the exposed group was 141 per 100,000 person years, which was a risk greater than 20-fold (adjusted hazard ratio 21.2.) They also observed a strong dose-effect relationship, with adjusted hazard ratio ranging from 5.0 to 31.1.

However, the risk of meningioma decreased noticeably after treatment was stopped. At 1 year after discontinuing treatment, the risk of meningioma in the exposed group was 1.8-fold higher (1.0 to 3.2) than in the control group.

Dr. Weill noted the clinical implications of these findings: clinicians need to inform patients who have used high-dose cyproterone acetate for at least 3-5 years about the increased risk of intracranial meningioma, he said.  

“The indication of cyproterone acetate should be clearly defined and the lowest possible daily dose used,” he said. “In the context of prolonged use of high-dose cyproterone acetate, magnetic resonance imaging screening for meningioma should be considered.”

“In patients with a documented meningioma, cyproterone acetate should be discontinued because the meningioma might regress in response to treatment discontinuation and invasive treatment could be avoided,” Dr. Weill added.
 

Use only when necessary

Weighing in on the research, Adilia Hormigo, MD, PhD, director of neuro-oncology at The Tisch Cancer Institute at Mount Sinai Health System in New York, noted that, “it is well known that there are sex differences in the incidence of meningiomas, as they are more frequent in women than men, and there is an association between breast cancer and the occurrence of meningiomas.”

Progesterone and androgen receptors have been found in meningiomas, she said in an interview, and there is no consensus regarding estrogen receptors. “In addition, hormonal therapy to inhibit estrogen or progesterone receptors has not produced any decrease in meningiomas’ growth,” she said.

The current study revealed an association between prolonged use of cyproterone acetate with an increased incidence of meningiomas, and the sphenoid-orbital meningioma location was specific for the drug use. “It is unclear from the study if all the meningiomas were benign,” she said. “Even if they are benign, they can cause severe morbidity, including seizures.”

Dr. Hormigo recommended that an MRI be performed on any patient who is taking a long course of cyproterone acetate in order to evaluate the development of meningiomas or meningioma progression. “And the drug should only be used when necessary,” she added.

This research was funded by the French National Health Insurance Fund and the Health Product Epidemiology Scientific Interest Group. Dr. Weill is an employee of the French National Health Insurance Fund, as are several other coauthors. The other authors have disclosed no relevant financial relationships. Dr. Hormigo has disclosed no relevant financial relationships.

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

New details confirm an increased risk of developing intracranial meningiomas after prolonged use of the hormonal product cyproterone acetate.

Cyproterone acetate is a synthetic progestogen and potent antiandrogen that has been used in the treatment of hirsutism, alopecia, early puberty, amenorrhea, acne, and prostate cancer, and has also been combined with an estrogen in hormone replacement therapy.

The new findings were published online in the BMJ. The primary analysis showed that, among women using cyproterone acetate, the rate of meningiomas was 23.8 per 100,000 person years vs. 4.5 per 100,000 in the control group. After adjusting for confounders, cyproterone acetate was associated with a sevenfold increased risk of meningioma.

These were young women – the mean age of participants was 29.4 years, and more than 40% of the cohort were younger than 25 years. The initial prescriber was a gynecologist for more than half (56.7%) of the participants, and 31.6% of prescriptions could correspond to the treatment of acne without hirsutism; 13.1% of prescriptions were compatible with management of hirsutism.

“Our study provides confirmation of the risk but also the measurement of the dose-effect relationship, the decrease in the risk after stopping use, and the preferential anatomical localization of meningiomas,” said lead author Alain Weill, MD, EPI-PHARE Scientific Interest Group, Saint-Denis, France.

“A large proportion of meningiomas involve the skull base, which is of considerable importance because skull base meningioma surgery is one of the most challenging forms of surgery and is associated with a much higher risk than surgery for convexity meningiomas,” he said in an interview.

Cyproterone acetate products have been available in Europe since the 1970s under various trade names and dose strengths (1, 2, 10, 50, and 100 mg), and marketed for various indications. These products are also marketed in many other industrialized nations, but not in the United States or Japan.

The link between cyproterone acetate and an increased risk of meningioma has been known for the past decade, and information on the risk of meningioma is already included in the prescribing information for cyproterone products.

Last year, the European Medicines Agency strengthened the warnings that were already in place and recommended that cyproterone products with daily doses of 10 mg or more be restricted because of the risk of developing meningioma.

“The recommendation from the EMA is a direct consequence of our study, that was sent to the EMA in summary form in 2018 and followed up with a very detailed with a report in summer 2019,” said Dr. Weill. “In light of this report, the European Medicines Agency recommended in February 2020 that drugs containing 10 mg or more of cyproterone acetate should only be used for hirsutism, androgenic alopecia, and acne and seborrhea once other treatment options have failed, including treatment with lower doses.”

Dr. Weill pointed out that two other epidemiologic studies have assessed the link between cyproterone acetate use and meningioma and showed an association. “Those studies and our own study are complementary and provide a coherent set of epidemiological evidence,” he said in the interview. “They show a documented risk for high-dose cyproterone acetate in men, women, and transgender people, and the absence of any observed risk for low-dose cyproterone acetate use in women.”
 

Strong dose-effect relationship

For their study, Dr. Weill and colleagues used data from the French administrative health care database. Between 2007 and 2014, 253,777 girls and women aged 7-70 years had begun using cyproterone acetate during that time period.

All participants had received at least one prescription for high-dose cyproterone acetate and did not have a history of meningioma, benign brain tumors, or long-term disease. They were considered to be exposed if they had received a cumulative dose of at least 3 g during the first 6 months (139,222 participants) and very slightly exposed (control group) when they had received a cumulative dose of less than 3 g (114,555 participants).

Overall, a total of 69 meningiomas were diagnosed in the exposed group (during 289,544 person years of follow-up) and 20 meningiomas in the control group (during 439,949 person years of follow-up). All were treated by surgery or radiotherapy.

When the analysis was done according to the cumulative dose, it showed a dose-effect relation, with a higher risk associated with a higher cumulative dose. The hazard ratio was not significant for exposure to less than 12 g of cyproterone acetate, but it jumped rapidly jumped as the dose climbed: The hazard ratio was 11.3 for 36-60 g and was 21.7 for 60 g or higher.

In a secondary analysis, the authors looked at the cohort who were already using cyproterone acetate in 2006 (n = 123,997). Women with long-term exposure were also taking estrogens more often (55.5% vs. 31.9%), and the incidence of meningioma in the exposed group was 141 per 100,000 person years, which was a risk greater than 20-fold (adjusted hazard ratio 21.2.) They also observed a strong dose-effect relationship, with adjusted hazard ratio ranging from 5.0 to 31.1.

However, the risk of meningioma decreased noticeably after treatment was stopped. At 1 year after discontinuing treatment, the risk of meningioma in the exposed group was 1.8-fold higher (1.0 to 3.2) than in the control group.

Dr. Weill noted the clinical implications of these findings: clinicians need to inform patients who have used high-dose cyproterone acetate for at least 3-5 years about the increased risk of intracranial meningioma, he said.  

“The indication of cyproterone acetate should be clearly defined and the lowest possible daily dose used,” he said. “In the context of prolonged use of high-dose cyproterone acetate, magnetic resonance imaging screening for meningioma should be considered.”

“In patients with a documented meningioma, cyproterone acetate should be discontinued because the meningioma might regress in response to treatment discontinuation and invasive treatment could be avoided,” Dr. Weill added.
 

Use only when necessary

Weighing in on the research, Adilia Hormigo, MD, PhD, director of neuro-oncology at The Tisch Cancer Institute at Mount Sinai Health System in New York, noted that, “it is well known that there are sex differences in the incidence of meningiomas, as they are more frequent in women than men, and there is an association between breast cancer and the occurrence of meningiomas.”

Progesterone and androgen receptors have been found in meningiomas, she said in an interview, and there is no consensus regarding estrogen receptors. “In addition, hormonal therapy to inhibit estrogen or progesterone receptors has not produced any decrease in meningiomas’ growth,” she said.

The current study revealed an association between prolonged use of cyproterone acetate with an increased incidence of meningiomas, and the sphenoid-orbital meningioma location was specific for the drug use. “It is unclear from the study if all the meningiomas were benign,” she said. “Even if they are benign, they can cause severe morbidity, including seizures.”

Dr. Hormigo recommended that an MRI be performed on any patient who is taking a long course of cyproterone acetate in order to evaluate the development of meningiomas or meningioma progression. “And the drug should only be used when necessary,” she added.

This research was funded by the French National Health Insurance Fund and the Health Product Epidemiology Scientific Interest Group. Dr. Weill is an employee of the French National Health Insurance Fund, as are several other coauthors. The other authors have disclosed no relevant financial relationships. Dr. Hormigo has disclosed no relevant financial relationships.

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