Cannabis use that interferes with a woman’s ability to function during pregnancy is a risk factor for severe health problems in the child, new research indicates.

Pregnant women with cannabis use disorder are more likely to have children with low birth weights and children who die within 1 year of birth, compared with matched controls, according to a study published online in Addiction.

The death rate among infants exposed to prenatal cannabis use disorder was 0.98%, compared with 0.75% among infants whose mothers did not have this diagnosis.

Cannabis use disorder during pregnancy “has increased dramatically in the past two decades,” but few studies have examined the health impacts on offspring, study author Yuyan Shi, PhD, said in an interview. “It is particularly concerning in states with cannabis legalization where cannabis is increasingly available.”

Dr. Shi, a researcher at the Herbert Wertheim School of Public Health and Human Longevity Science at the University of California, San Diego, and colleagues analyzed data from more than 4.8 million mothers who delivered a live singleton birth in California between 2001 and 2012 and their infants. They focused on 20,237 mothers who had a diagnosis of cannabis use disorder at delivery. The disorder is defined by continued use of the drug despite impairments in physical, psychological, and social functioning.

The researchers matched mothers with cannabis use disorder 1:2 to mothers who did not have this diagnosis. They aimed to balance factors such as maternal age, educational attainment, health insurance, physical and mental health conditions, prenatal care, and alcohol and opioid use disorder.
 

An increasingly common diagnosis

Over the study period, the rate of cannabis use disorder increased from 2.8 cases per 1,000 deliveries in 2001 to 6.9 cases per 1,000 deliveries in 2012.

Cannabis use disorder was associated with increased odds of preterm birth (odds ratio, 1.06), small for gestational age (OR, 1.13), low birth weight (OR, 1.13), and death within 1 year of birth (OR, 1.35), according to the researchers’ estimates. Cannabis use disorder was associated with lower odds of hospitalization within 1 year of birth, however (OR, 0.91).

“The most notable observation is that exposed infants were 35% more likely to die within 1 year of birth than unexposed infants,” Dr. Shi and colleagues wrote. More research is needed to understand the causes of death at different stages of infancy, they said.

The results “imply that cannabis use disorder screening as well as appropriate education, counseling, or referral to substance abuse treatment services should be encouraged among pregnant women,” Dr. Shi said.

The study does not establish that cannabis use disorder causes adverse effects, and it is not clear how the results might apply to mothers who use cannabis but do not meet diagnostic criteria for the disorder, the authors noted.

“Presumably the health consequences of mothers who use cannabis but do not meet the criteria ... are less severe than mothers with cannabis use disorder,” Dr. Shi said. “Unfortunately, no research has been conducted to test this hypothesis.”
 

Enough data to recommend abstaining

Many clinicians may not feel equipped to make a diagnosis of cannabis use disorder, said Jamie Lo, MD, assistant professor of obstetrics and gynecology at Oregon Health and Science University in Portland.

Although many clinicians ask patients about substance use in general, specifically screening for cannabis use is not necessarily routine practice. “I think people are starting to adopt that, but it probably will take a little bit of time,” Dr. Lo said.

Dr. Lo, who was not involved in the study, researches the effects of marijuana during pregnancy.

Confounding factors such as frequent co-use of tobacco have so far made it “difficult to suss out” whether observed effects are directly from cannabis use, other substances or exposures, or a combination, said Dr. Lo. The possibility that stigma may lead to inaccurate self-reporting poses another challenge. And the range of cannabis delivery devices further complicates matters.

“It is hard to compare smoking a bowl versus a joint versus using the oils or CBD or edibles,” Dr. Lo said. The data regarding cigarettes and alcohol are cleaner and more precise, in comparison.

Still, federal agencies and professional societies agree that “what we do know is enough to recommend that pregnant women abstain from using cannabis during pregnancy,” Dr. Lo said.

The National Institute on Drug Abuse, which funded the study, said the results add to the evidence that prenatal exposure to cannabis may be associated with poor birth outcomes and infant health.

“While we cannot establish that cannabis use caused negative outcomes in this study, these data reinforce the case for caution around using cannabis during pregnancy,” Nora D. Volkow, MD, the director of the agency, said in a news release.

“Careful analysis of data like these is one way we can responsibly study how cannabis use affects the developing child, all while a natural experiment is playing out across our country in places where cannabis is becoming widely available to pregnant consumers.”

The study authors and Dr. Lo had no disclosures.

[email protected]

Cannabis use that interferes with a woman’s ability to function during pregnancy is a risk factor for severe health problems in the child, new research indicates.

Pregnant women with cannabis use disorder are more likely to have children with low birth weights and children who die within 1 year of birth, compared with matched controls, according to a study published online in Addiction.

The death rate among infants exposed to prenatal cannabis use disorder was 0.98%, compared with 0.75% among infants whose mothers did not have this diagnosis.

Cannabis use disorder during pregnancy “has increased dramatically in the past two decades,” but few studies have examined the health impacts on offspring, study author Yuyan Shi, PhD, said in an interview. “It is particularly concerning in states with cannabis legalization where cannabis is increasingly available.”

Dr. Shi, a researcher at the Herbert Wertheim School of Public Health and Human Longevity Science at the University of California, San Diego, and colleagues analyzed data from more than 4.8 million mothers who delivered a live singleton birth in California between 2001 and 2012 and their infants. They focused on 20,237 mothers who had a diagnosis of cannabis use disorder at delivery. The disorder is defined by continued use of the drug despite impairments in physical, psychological, and social functioning.

The researchers matched mothers with cannabis use disorder 1:2 to mothers who did not have this diagnosis. They aimed to balance factors such as maternal age, educational attainment, health insurance, physical and mental health conditions, prenatal care, and alcohol and opioid use disorder.
 

An increasingly common diagnosis

Over the study period, the rate of cannabis use disorder increased from 2.8 cases per 1,000 deliveries in 2001 to 6.9 cases per 1,000 deliveries in 2012.

Cannabis use disorder was associated with increased odds of preterm birth (odds ratio, 1.06), small for gestational age (OR, 1.13), low birth weight (OR, 1.13), and death within 1 year of birth (OR, 1.35), according to the researchers’ estimates. Cannabis use disorder was associated with lower odds of hospitalization within 1 year of birth, however (OR, 0.91).

“The most notable observation is that exposed infants were 35% more likely to die within 1 year of birth than unexposed infants,” Dr. Shi and colleagues wrote. More research is needed to understand the causes of death at different stages of infancy, they said.

The results “imply that cannabis use disorder screening as well as appropriate education, counseling, or referral to substance abuse treatment services should be encouraged among pregnant women,” Dr. Shi said.

The study does not establish that cannabis use disorder causes adverse effects, and it is not clear how the results might apply to mothers who use cannabis but do not meet diagnostic criteria for the disorder, the authors noted.

“Presumably the health consequences of mothers who use cannabis but do not meet the criteria ... are less severe than mothers with cannabis use disorder,” Dr. Shi said. “Unfortunately, no research has been conducted to test this hypothesis.”
 

Enough data to recommend abstaining

Many clinicians may not feel equipped to make a diagnosis of cannabis use disorder, said Jamie Lo, MD, assistant professor of obstetrics and gynecology at Oregon Health and Science University in Portland.

Although many clinicians ask patients about substance use in general, specifically screening for cannabis use is not necessarily routine practice. “I think people are starting to adopt that, but it probably will take a little bit of time,” Dr. Lo said.

Dr. Lo, who was not involved in the study, researches the effects of marijuana during pregnancy.

Confounding factors such as frequent co-use of tobacco have so far made it “difficult to suss out” whether observed effects are directly from cannabis use, other substances or exposures, or a combination, said Dr. Lo. The possibility that stigma may lead to inaccurate self-reporting poses another challenge. And the range of cannabis delivery devices further complicates matters.

“It is hard to compare smoking a bowl versus a joint versus using the oils or CBD or edibles,” Dr. Lo said. The data regarding cigarettes and alcohol are cleaner and more precise, in comparison.

Still, federal agencies and professional societies agree that “what we do know is enough to recommend that pregnant women abstain from using cannabis during pregnancy,” Dr. Lo said.

The National Institute on Drug Abuse, which funded the study, said the results add to the evidence that prenatal exposure to cannabis may be associated with poor birth outcomes and infant health.

“While we cannot establish that cannabis use caused negative outcomes in this study, these data reinforce the case for caution around using cannabis during pregnancy,” Nora D. Volkow, MD, the director of the agency, said in a news release.

“Careful analysis of data like these is one way we can responsibly study how cannabis use affects the developing child, all while a natural experiment is playing out across our country in places where cannabis is becoming widely available to pregnant consumers.”

The study authors and Dr. Lo had no disclosures.

[email protected]

Cannabis use that interferes with a woman’s ability to function during pregnancy is a risk factor for severe health problems in the child, new research indicates.

Pregnant women with cannabis use disorder are more likely to have children with low birth weights and children who die within 1 year of birth, compared with matched controls, according to a study published online in Addiction.

The death rate among infants exposed to prenatal cannabis use disorder was 0.98%, compared with 0.75% among infants whose mothers did not have this diagnosis.

Cannabis use disorder during pregnancy “has increased dramatically in the past two decades,” but few studies have examined the health impacts on offspring, study author Yuyan Shi, PhD, said in an interview. “It is particularly concerning in states with cannabis legalization where cannabis is increasingly available.”

Dr. Shi, a researcher at the Herbert Wertheim School of Public Health and Human Longevity Science at the University of California, San Diego, and colleagues analyzed data from more than 4.8 million mothers who delivered a live singleton birth in California between 2001 and 2012 and their infants. They focused on 20,237 mothers who had a diagnosis of cannabis use disorder at delivery. The disorder is defined by continued use of the drug despite impairments in physical, psychological, and social functioning.

The researchers matched mothers with cannabis use disorder 1:2 to mothers who did not have this diagnosis. They aimed to balance factors such as maternal age, educational attainment, health insurance, physical and mental health conditions, prenatal care, and alcohol and opioid use disorder.
 

An increasingly common diagnosis

Over the study period, the rate of cannabis use disorder increased from 2.8 cases per 1,000 deliveries in 2001 to 6.9 cases per 1,000 deliveries in 2012.

Cannabis use disorder was associated with increased odds of preterm birth (odds ratio, 1.06), small for gestational age (OR, 1.13), low birth weight (OR, 1.13), and death within 1 year of birth (OR, 1.35), according to the researchers’ estimates. Cannabis use disorder was associated with lower odds of hospitalization within 1 year of birth, however (OR, 0.91).

“The most notable observation is that exposed infants were 35% more likely to die within 1 year of birth than unexposed infants,” Dr. Shi and colleagues wrote. More research is needed to understand the causes of death at different stages of infancy, they said.

The results “imply that cannabis use disorder screening as well as appropriate education, counseling, or referral to substance abuse treatment services should be encouraged among pregnant women,” Dr. Shi said.

The study does not establish that cannabis use disorder causes adverse effects, and it is not clear how the results might apply to mothers who use cannabis but do not meet diagnostic criteria for the disorder, the authors noted.

“Presumably the health consequences of mothers who use cannabis but do not meet the criteria ... are less severe than mothers with cannabis use disorder,” Dr. Shi said. “Unfortunately, no research has been conducted to test this hypothesis.”
 

Enough data to recommend abstaining

Many clinicians may not feel equipped to make a diagnosis of cannabis use disorder, said Jamie Lo, MD, assistant professor of obstetrics and gynecology at Oregon Health and Science University in Portland.

Although many clinicians ask patients about substance use in general, specifically screening for cannabis use is not necessarily routine practice. “I think people are starting to adopt that, but it probably will take a little bit of time,” Dr. Lo said.

Dr. Lo, who was not involved in the study, researches the effects of marijuana during pregnancy.

Confounding factors such as frequent co-use of tobacco have so far made it “difficult to suss out” whether observed effects are directly from cannabis use, other substances or exposures, or a combination, said Dr. Lo. The possibility that stigma may lead to inaccurate self-reporting poses another challenge. And the range of cannabis delivery devices further complicates matters.

“It is hard to compare smoking a bowl versus a joint versus using the oils or CBD or edibles,” Dr. Lo said. The data regarding cigarettes and alcohol are cleaner and more precise, in comparison.

Still, federal agencies and professional societies agree that “what we do know is enough to recommend that pregnant women abstain from using cannabis during pregnancy,” Dr. Lo said.

The National Institute on Drug Abuse, which funded the study, said the results add to the evidence that prenatal exposure to cannabis may be associated with poor birth outcomes and infant health.

“While we cannot establish that cannabis use caused negative outcomes in this study, these data reinforce the case for caution around using cannabis during pregnancy,” Nora D. Volkow, MD, the director of the agency, said in a news release.

“Careful analysis of data like these is one way we can responsibly study how cannabis use affects the developing child, all while a natural experiment is playing out across our country in places where cannabis is becoming widely available to pregnant consumers.”

The study authors and Dr. Lo had no disclosures.

[email protected]

ABSTRACT

Purpose Medical scribes are known to increase revenue by increasing visits to a medical practice. We examined whether medical scribes are associated with markers of financial benefit independent of increased visits.

Methods We conducted a pre- and post-­observational study with a control group, examining changes in the percentage of visits (1) coded as level of service 4 or 5, (2) with at least 1 hierarchical condition category code billed, and (3) at which orders for 3 pay-for-performance quality measures (screening for breast, cervical, and colon cancer) were placed, if due. We looked at changes in outcomes among scribed providers and compared them to nonscribed providers. We used generalized estimating equations with robust standard errors to account for repeated measures and the hierarchical nature of the data, controlling for patient demographics.

Results We examined 41,371 visits to 17 scribed providers and 230,297 visits to 78 nonscribed providers. In adjusted analyses, and compared to nonscribed providers, scribes were associated with an increase of:

• Frutiger LT Std9.2 percentage points in level-of-­service 4 or 5 billing (Frutiger LT StdP < .001)
• 3.6 percentage points in hierarchical condition category coding (Frutiger LT StdP < .001)
• 4.0 percentage points in breast cancer screening orders (Frutiger LT StdP = .01)
• 4.9 percentage points in colon cancer screening orders (Frutiger LT StdPFrutiger LT Std = .04).

Conclusions This study suggests that scribes are associated with financial benefit in addition to increased visit volume. Primary care practices should consider the financial benefit of scribes independent of their ability to add patient volume.

Increasingly, medical scribes are used in ambulatory care settings across the United States.¹ Scribes are trained personnel who accompany providers during visits to provide documentation support and assist with other administrative tasks. They are associated with reduced documentation time for providers^2-6 and improved provider satisfaction,^7-11 without detriment to^4-16 (or with possible improvement in^17-20) patient satisfaction in ambulatory care settings. At the same time, concerns remain that using scribes might inhibit patient communication, harm clinical reasoning, reduce the effectiveness of clinical decision-support tools, and simply serve as a work-around to fixing inefficiencies in the electronic medical record (EMR).^21-23

A driving force for the increased use of medical scribes is the expectation that they reduce the cost of providing care. Cost-­efficiency is typically described as resulting from a reduction in physician time per patient seen, which allows increased patient volume and, in turn, drives increased physician productivity.^{2,8,10,18,24-27} Whether scribes result in cost savings remains unclear; some papers suggest that scribes are cost efficient in ambulatory care,^2,10,18 while others have been unable to identify cost savings, particularly in primary care.⁴

One reason why scribes might not be associated with cost savings is that their financial benefit might be undercounted. Studies that focus on increased volume miss the opportunity to capture financial benefits conferred through mechanisms that are independent of seeing more patients:

• Scribes might help providers address and document more, and more complex, medical problems, allowing higher level-of-service (LOS) billing. For example, a provider chooses a lower LOS because they have insufficiently documented a visit to support a higher LOS; by assisting with documentation, the scribe might allow the provider to choose a higher LOS.
• Scribes might prompt a provider to use decision-support tools for risk coding (using appropriate medical codes to capture the patient’s level of medical complexity), thereby increasing reimbursement.
• Scribes might extend the time available during the visit for the provider to address pay-for-performance quality measures, such as cancer screening.

Continue to: Making visits count, not counting visits

Making visits count, not counting visits. In this study, we examined whether medical scribes in primary care are associated with improved markers of revenue that are independent of seeing more patients. Specifically, we examined whether scribes are associated with increased LOS coding, risk coding, and orders for pay-for-performance measures for all primary care visits and for nonpreventive primary care visits.

Methods

Design

This observational study compared the change in outcomes before implementation of scribes and during implementation of scribes, between scribed providers and nonscribed providers. We compared visits during the year prior to the implementation of scribes (July 2017–June 2018) with the year during their implementation (July 2018–2019).

The Cambridge Health Alliance Institutional Review Board considered this study exempt from review.

Setting

This study was conducted at a safety-net community academic health system that uses an EMR developed by Epic Systems [Verona, WI]. This EMR includes decision-support tools that prompt providers when pay-for-performance quality measures are due and when hierarchical condition category (HCC) codes—ie, specific diagnoses used by Medicare and other payers to reimburse providers for the complexity of their patients—might apply to the visit.

Primary care practices should consider the financial benefit of scribes, independent of their ability to add patient volume.

These EMR decision-support tools use algorithms that draw on age, gender, diagnoses that were billed previously or are on the problem list, laboratory findings, and prior imaging. They alert physicians when a patient is due for pay-for-performance quality measures, such as cancer screenings, and when HCC codes might be applicable.

Continue to: During the study period...

During the study period, the EMR ­decision-support tool for HCC coding underwent several changes designed to improve HCC coding. In addition, systematic changes to primary care visits took place, leading to an increase in the number of patients seen and screenings required.

Outcomes

We examined 2 categories of outcomes that confer financial benefit to many institutions: billing measures and pay-for-performance measures.

Billing measures included the percentage of visits (1) coded as LOS 4 or 5 and (2) with at least 1 HCC code billed (among those for which the decision-support tool identified at least 1 potential HCC code).

Pay-for-performance measures. We examined whether any of 3 pay-for-­performance quality measures were addressed during the visit, selecting 3 that are commonly addressed by primary care providers (PCPs) and that require PCPs to sign an order for screening during a primary care visit: breast cancer (mammography order), cervical cancer (Papanicolaou smear order), and colon cancer (an order for fecal occult blood testing or colonoscopy).

Intervention

Scribes were employees of Cambridge Health Alliance who had recently graduated from college and were interested in a career as a health care professional. Scribes received 3 days of training on how to function effectively in their role; 1 day of training in EMR functionality; and 2 hours of training on decision-support tools for pay-for-performance quality measures and risk coding. Scribes continued learning on the job through feedback from supervising PCPs. Scribes documented patient encounters, recording histories and findings on the physical exam and transcribing discussion of treatment plans and the PCP’s instructions to patients.

Continue to: The 14 scribes worked with 17 physician...

The 14 scribes worked with 17 physician and nurse practitioner PCPs beginning in July 2018. Participation by PCPs was voluntary; they received no compensation for participating in the scribe program. PCPs were not required to see additional patients to participate. PCPs who chose to work with a scribe were similar to those who declined a scribe, as regards gender, race, type of provider (MD or NP), tenure at the institution, and percentage of time in clinical work (see Table W-1).

The control group comprised providers who elected not to work with a scribe but who worked in the same clinics as the intervention providers.

Scribes might extend the time available during the visit for the provider to address pay-forperformance quality measures, such as cancer screening.

Scribes were assigned to a PCP based on availability during the PCP’s scheduled hours and worked with 1 PCP throughout the intervention (except for 1 PCP who worked with 2 scribes). All PCPs worked with their scribe(s) part time; on average, 49% of intervention PCPs’ visits were scribed.

Inclusion and exclusion criteria

Because the first year at an institution is a learning period for PCPs, we excluded those who worked at the institution for < 1 year before the start of the scribe program (n = 12). Based on the extensive clinical experience of 1 PCP (WA) with scribes, we excluded the first 200 visits or 6 weeks (whichever occurred first) with a scribe among all scribed providers, to account for an initial learning period (n = 2202, of 15,372 scribed visits [14%]). We also excluded 2 providers who left during the pre-intervention period or were in the intervention period for < 1 month.

To ensure that we captured visits to providers with clinically significant exposure to scribes, we required scribed providers to have ≥ 20% of their visits scribed during the intervention period. To minimize the potential for contamination, we excluded nonscribed visits to scribed providers during the intervention period (n = 2211), because such nonscribed visits were largely due to visits outside the scribe’s scheduled time.

Continue to: Analysis

We compared demographic characteristics for patients and providers using the chi-square test for categorical variables and the t test for continuous variables. We compared the change in outcomes from before implementation of scribes to during implementation of scribes among scribed providers, compared to nonscribed providers, using generalized estimating equations with robust standard errors to account for repeated measures (ie, multiple visits by the same patients) and the hierarchical nature of the data (ie, patients nested within providers). We then recalculated these estimates, controlling for patient demographics (age, gender, race, and ethnicity). We repeated these analyses for patients presenting for nonpreventive visits.

Results

Visit characteristics

We examined 271,768 visits, including 41,371 visits to 17 scribed providers and 230,397 visits to 78 nonscribed providers (Table 1). Patients were most likely to be female, > 21 years of age, have English as their language of care, and be non-White. Most visits were by established patients and were nonpreventive.

We noted no clinically significant differences in characteristics between visits with scribed providers and visits with nonscribed providers, and over time. Patient complexity measures, including care management enrollment and hospital admissions, were also similar between groups, and over time.

Billing measures

HCC coding. In 28.6% of visits, the decision-support tool identified at least 1 potential HCC code. Among these, the percentage of visits with at least 1 HCC code billed increased by 10.1 percentage points (from 3.9% before implementation of scribes to 14.0%) among scribed providers, compared to increasing by 6.5 percentage points (from 2.9% before implementation to 9.3%) among nonscribed providers (TABLE 2). Scribes were therefore associated with an additional 3.6 percentage-point increase in visits with at least 1 HCC code billed (P < .0001)—a difference that remained significant after adjusting for patient demographics (P < .0001).

LOS coding. Scribed providers increased the number of visits billed as LOS 4 or 5 by 9.6 percentage points (from 47.3% before implementation to 56.8%); during the same period, nonscribed providers increased the number of visits billed as LOS 4 or 5 by 1.3 percentage points (from 46.5% before implementation to 47.8%) (TABLE 2). Scribes were therefore associated with an additional 8.3 percentage points in LOS 4 or 5 billing (P < .001) (TABLE 2). This difference remained significant after adjusting for patient demographics (P < .001).

Continue to: Pay-for-performance quality measures

Breast cancer screening. Scribed providers increased the number of visits at which breast cancer screening was ordered by 2.7 percentage points (from 17.3% before implementation of scribes to 20.0%); during the same period, the number of visits at which breast cancer screening was ordered by nonscribed providers decreased by 1.9 percentage points (from 19.5% to 17.6%). Scribes were therefore associated with an increase of 4.6 percentage points in breast cancer screening orders, compared to nonscribed providers (P < .003) (TABLE 2). That difference remained significant after adjusting for patient demographics (P = .01).

Colon cancer screening. Similarly, scribed providers increased the number of visits at which colon cancer screening was ordered by 1.2 percentage points (from 19.2% before implementation of scribes to 20.3%); during the same period, the number of visits at which colon cancer screening was ordered by nonscribed providers decreased by 2.7 percentage points (from 18.5% to 15.9%) (P = .112). After adjusting for patient demographics, scribes were associated with an increase of 4.9 percentage points in colon cancer screening orders, compared to nonscribed providers (P = .044) (TABLE 2).

Cervical cancer screening. The rate at which cervical cancer screening was ordered did not change among scribed providers and decreased (by 2.5 percentage points) among nonscribed providers—a difference that was not statistically significant (P = .26).

Nonpreventive visits. Our findings overall did not change in analyses focused on nonpreventive visits, in which scribes were associated with an increase of 8.2 percentage points in LOS 4 or 5 billing (P < .001); an increase of 3.1 percentage points in HCC coding (P < .001); and an increase of 3.2 percentage points in breast cancer screening orders (P = .03) (TABLE 3). Although scribes were associated with an increase of 1.5 percentage points in cervical cancer screening orders and an increase of 3.1 percentage points in colon cancer screening orders, these increases did not reach statistical significance.

Discussion

We found that implementation of scribes is associated with (1) an increase in LOS coding and risk coding and (2) a higher frequency of addressing 2 of 3 pay-for-performance quality measures in primary care. In adjusted analyses in our study, and compared to nonscribed providers, scribes were associated with an additional 9.2 percentage points in LOS 4 or 5 billing; 3.6 percentage points in HCC coding; 4.0 percentage points in breast cancer screening orders; and 4.9 percentage points in colon cancer screening orders. Cervical cancer screening orders followed a similar pattern, with an increase of 2.3 percentage points in the adjusted screening order rate among scribed providers, compared to nonscribed providers, during implementation of scribes—although the increase was not significant. These findings did not change in analyses focused on nonpreventive visits.

Continue to: Our findings are consistent

Our findings are consistent with those of earlier studies. Prior examinations in ambulatory specialties found that scribes increased HCC coding,⁴ LOS billing,²⁴ and pay-for-performance metrics.¹⁸ The only study to examine these areas in primary care found that scribes were associated with increased pay-for-performance measure documentation,²⁰ a change that is necessary but insufficient to realize increased pay-for-­performance revenue. Therefore, our study confirms, for the first time, that PCPs can better address pay-for-performance measures, LOS billing, and HCC coding when working with a scribe in primary care.

Providers who used a scribe during the intervention period of our study increased the number of visits billed as LOS 4 or 5 by 9.6 percentage points.

Demands on primary care visits are increasing.²⁸ Physicians are required to provide more documentation; there is greater emphasis on PCPs meeting pay-for-­performance measures; and there are more data in the EMR to review. In this context, addressing pay-for-performance measures and gaps in risk coding is likely to be increasingly challenging. Our study suggests that scribes might provide a mechanism to increase risk coding, LOS billing, and pay-for-performance measures, despite increased demands on primary care visits.

Increase in LOS billing. In the settings in which we work, a fee-for-service LOS 4 primary care visit generates, on average, $20 to $75 more in revenue than an LOS 3 visit. Using an average of $50 additional revenue for LOS 4 billing, we estimate that a full-time scribe is associated with roughly $7,000 in additional revenue annually. We arrived at this estimate using an average of 1500 visits at LOS ≤ 3 for every PCP full-time equivalent. A 9.2 percentage–point increase in LOS 4 billing would lead to roughly 140 additional LOS 4 visits, with each visit generating an additional $50 in revenue.

This analysis does not account for increased revenue associated with increased pay for HCC coding identified in our study.

Our study also suggests that scribes might provide a mechanism to increase risk coding and payfor-performance, despite increased demands on primary care visits.

Furthermore, in our conservative assumption, the entire increase in LOS billing was from level 3 to level 4; in fact, a small percentage of that increase would be from level 2 and another small percentage would be to level 5—both of which would generate additional revenue. Our assumption therefore underestimates the full financial value associated with scribes in the absence of increased patient volume. Nonetheless, the assumption suggests that increases in LOS billing offset a substantial percentage of a scribe’s salary.

Continue to: Limitations of this study

Limitations of this study. Our study should be interpreted in the context of several limitations:

• The study was conducted at 1 institution. Our findings might not be generalizable beyond this setting.
• The study measures the impact of scribes when providers work with scribes part time. Because providers who utilize a scribe for all, or nearly all, their visits are likely to use a scribe more efficiently, our study might underestimate the full impact of a scribe.
• In some settings, team members such as medical assistants are trained to assist with documentation and other responsibilities (such as closing care gaps) in addition to other patient care responsibilities.^29-32 The extent to which our findings transfer to other models is unclear; studies comparing the impact of other models (which might provide even stronger outcomes) to the impact of medical scribes would be an interesting area for further research.
• In addition to the variability of models, there is likely variability in the quality and interactions of medical scribes, which might impact outcomes. We did not examine the qualities of scribes that led to outcomes in this study.
• We examined the impact of scribes on quality measure–ordering behaviors of providers, not on whether quality measures actually improved. Because scribes are associated with more face-to-face time with patients,²⁷ they might allow for increased attention being paid by physicians to barriers to pay-for-performance measures (eg, patient education). This could increase the likelihood that patients complete a multitude of screenings, and thus improve adherence and follow-up. However, the impact of scribes on quality measures is a topic for future study.

Value beyond volume. Any limitations notwithstanding, our study suggests that scribes are associated with financial benefit in addition to the benefit of increased volume. Primary care practices should therefore consider the financial benefit of scribes independent of their ability to add patient volume. By recognizing this additive value, primary care practices might more fully capture the benefit of scribes, which might then allow practices to employ scribes with less demand to increase volume. This added support without increased volume would, in turn, likely reduce provider burnout (and the costly associated turnover) and increase patient satisfaction, leading to a synergistic financial benefit.

CORRESPONDENCE
Wayne Altman, MD, FAAFP, Tufts University School of Medicine, 200 Harrison Avenue, Boston, MA 02111; wayne. [email protected]

ABSTRACT

Purpose Medical scribes are known to increase revenue by increasing visits to a medical practice. We examined whether medical scribes are associated with markers of financial benefit independent of increased visits.

Methods We conducted a pre- and post-­observational study with a control group, examining changes in the percentage of visits (1) coded as level of service 4 or 5, (2) with at least 1 hierarchical condition category code billed, and (3) at which orders for 3 pay-for-performance quality measures (screening for breast, cervical, and colon cancer) were placed, if due. We looked at changes in outcomes among scribed providers and compared them to nonscribed providers. We used generalized estimating equations with robust standard errors to account for repeated measures and the hierarchical nature of the data, controlling for patient demographics.

Results We examined 41,371 visits to 17 scribed providers and 230,297 visits to 78 nonscribed providers. In adjusted analyses, and compared to nonscribed providers, scribes were associated with an increase of:

• Frutiger LT Std9.2 percentage points in level-of-­service 4 or 5 billing (Frutiger LT StdP < .001)
• 3.6 percentage points in hierarchical condition category coding (Frutiger LT StdP < .001)
• 4.0 percentage points in breast cancer screening orders (Frutiger LT StdP = .01)
• 4.9 percentage points in colon cancer screening orders (Frutiger LT StdPFrutiger LT Std = .04).

Conclusions This study suggests that scribes are associated with financial benefit in addition to increased visit volume. Primary care practices should consider the financial benefit of scribes independent of their ability to add patient volume.

Increasingly, medical scribes are used in ambulatory care settings across the United States.¹ Scribes are trained personnel who accompany providers during visits to provide documentation support and assist with other administrative tasks. They are associated with reduced documentation time for providers^2-6 and improved provider satisfaction,^7-11 without detriment to^4-16 (or with possible improvement in^17-20) patient satisfaction in ambulatory care settings. At the same time, concerns remain that using scribes might inhibit patient communication, harm clinical reasoning, reduce the effectiveness of clinical decision-support tools, and simply serve as a work-around to fixing inefficiencies in the electronic medical record (EMR).^21-23

A driving force for the increased use of medical scribes is the expectation that they reduce the cost of providing care. Cost-­efficiency is typically described as resulting from a reduction in physician time per patient seen, which allows increased patient volume and, in turn, drives increased physician productivity.^{2,8,10,18,24-27} Whether scribes result in cost savings remains unclear; some papers suggest that scribes are cost efficient in ambulatory care,^2,10,18 while others have been unable to identify cost savings, particularly in primary care.⁴

One reason why scribes might not be associated with cost savings is that their financial benefit might be undercounted. Studies that focus on increased volume miss the opportunity to capture financial benefits conferred through mechanisms that are independent of seeing more patients:

• Scribes might help providers address and document more, and more complex, medical problems, allowing higher level-of-service (LOS) billing. For example, a provider chooses a lower LOS because they have insufficiently documented a visit to support a higher LOS; by assisting with documentation, the scribe might allow the provider to choose a higher LOS.
• Scribes might prompt a provider to use decision-support tools for risk coding (using appropriate medical codes to capture the patient’s level of medical complexity), thereby increasing reimbursement.
• Scribes might extend the time available during the visit for the provider to address pay-for-performance quality measures, such as cancer screening.

Continue to: Making visits count, not counting visits

Making visits count, not counting visits. In this study, we examined whether medical scribes in primary care are associated with improved markers of revenue that are independent of seeing more patients. Specifically, we examined whether scribes are associated with increased LOS coding, risk coding, and orders for pay-for-performance measures for all primary care visits and for nonpreventive primary care visits.

Methods

Design

This observational study compared the change in outcomes before implementation of scribes and during implementation of scribes, between scribed providers and nonscribed providers. We compared visits during the year prior to the implementation of scribes (July 2017–June 2018) with the year during their implementation (July 2018–2019).

The Cambridge Health Alliance Institutional Review Board considered this study exempt from review.

Setting

This study was conducted at a safety-net community academic health system that uses an EMR developed by Epic Systems [Verona, WI]. This EMR includes decision-support tools that prompt providers when pay-for-performance quality measures are due and when hierarchical condition category (HCC) codes—ie, specific diagnoses used by Medicare and other payers to reimburse providers for the complexity of their patients—might apply to the visit.

Primary care practices should consider the financial benefit of scribes, independent of their ability to add patient volume.

These EMR decision-support tools use algorithms that draw on age, gender, diagnoses that were billed previously or are on the problem list, laboratory findings, and prior imaging. They alert physicians when a patient is due for pay-for-performance quality measures, such as cancer screenings, and when HCC codes might be applicable.

Continue to: During the study period...

During the study period, the EMR ­decision-support tool for HCC coding underwent several changes designed to improve HCC coding. In addition, systematic changes to primary care visits took place, leading to an increase in the number of patients seen and screenings required.

Outcomes

We examined 2 categories of outcomes that confer financial benefit to many institutions: billing measures and pay-for-performance measures.

Billing measures included the percentage of visits (1) coded as LOS 4 or 5 and (2) with at least 1 HCC code billed (among those for which the decision-support tool identified at least 1 potential HCC code).

Pay-for-performance measures. We examined whether any of 3 pay-for-­performance quality measures were addressed during the visit, selecting 3 that are commonly addressed by primary care providers (PCPs) and that require PCPs to sign an order for screening during a primary care visit: breast cancer (mammography order), cervical cancer (Papanicolaou smear order), and colon cancer (an order for fecal occult blood testing or colonoscopy).

Intervention

Scribes were employees of Cambridge Health Alliance who had recently graduated from college and were interested in a career as a health care professional. Scribes received 3 days of training on how to function effectively in their role; 1 day of training in EMR functionality; and 2 hours of training on decision-support tools for pay-for-performance quality measures and risk coding. Scribes continued learning on the job through feedback from supervising PCPs. Scribes documented patient encounters, recording histories and findings on the physical exam and transcribing discussion of treatment plans and the PCP’s instructions to patients.

Continue to: The 14 scribes worked with 17 physician...

The 14 scribes worked with 17 physician and nurse practitioner PCPs beginning in July 2018. Participation by PCPs was voluntary; they received no compensation for participating in the scribe program. PCPs were not required to see additional patients to participate. PCPs who chose to work with a scribe were similar to those who declined a scribe, as regards gender, race, type of provider (MD or NP), tenure at the institution, and percentage of time in clinical work (see Table W-1).

The control group comprised providers who elected not to work with a scribe but who worked in the same clinics as the intervention providers.

Scribes might extend the time available during the visit for the provider to address pay-forperformance quality measures, such as cancer screening.

Scribes were assigned to a PCP based on availability during the PCP’s scheduled hours and worked with 1 PCP throughout the intervention (except for 1 PCP who worked with 2 scribes). All PCPs worked with their scribe(s) part time; on average, 49% of intervention PCPs’ visits were scribed.

Inclusion and exclusion criteria

Because the first year at an institution is a learning period for PCPs, we excluded those who worked at the institution for < 1 year before the start of the scribe program (n = 12). Based on the extensive clinical experience of 1 PCP (WA) with scribes, we excluded the first 200 visits or 6 weeks (whichever occurred first) with a scribe among all scribed providers, to account for an initial learning period (n = 2202, of 15,372 scribed visits [14%]). We also excluded 2 providers who left during the pre-intervention period or were in the intervention period for < 1 month.

To ensure that we captured visits to providers with clinically significant exposure to scribes, we required scribed providers to have ≥ 20% of their visits scribed during the intervention period. To minimize the potential for contamination, we excluded nonscribed visits to scribed providers during the intervention period (n = 2211), because such nonscribed visits were largely due to visits outside the scribe’s scheduled time.

Continue to: Analysis

We compared demographic characteristics for patients and providers using the chi-square test for categorical variables and the t test for continuous variables. We compared the change in outcomes from before implementation of scribes to during implementation of scribes among scribed providers, compared to nonscribed providers, using generalized estimating equations with robust standard errors to account for repeated measures (ie, multiple visits by the same patients) and the hierarchical nature of the data (ie, patients nested within providers). We then recalculated these estimates, controlling for patient demographics (age, gender, race, and ethnicity). We repeated these analyses for patients presenting for nonpreventive visits.

Results

Visit characteristics

We examined 271,768 visits, including 41,371 visits to 17 scribed providers and 230,397 visits to 78 nonscribed providers (Table 1). Patients were most likely to be female, > 21 years of age, have English as their language of care, and be non-White. Most visits were by established patients and were nonpreventive.

We noted no clinically significant differences in characteristics between visits with scribed providers and visits with nonscribed providers, and over time. Patient complexity measures, including care management enrollment and hospital admissions, were also similar between groups, and over time.

Billing measures

HCC coding. In 28.6% of visits, the decision-support tool identified at least 1 potential HCC code. Among these, the percentage of visits with at least 1 HCC code billed increased by 10.1 percentage points (from 3.9% before implementation of scribes to 14.0%) among scribed providers, compared to increasing by 6.5 percentage points (from 2.9% before implementation to 9.3%) among nonscribed providers (TABLE 2). Scribes were therefore associated with an additional 3.6 percentage-point increase in visits with at least 1 HCC code billed (P < .0001)—a difference that remained significant after adjusting for patient demographics (P < .0001).

LOS coding. Scribed providers increased the number of visits billed as LOS 4 or 5 by 9.6 percentage points (from 47.3% before implementation to 56.8%); during the same period, nonscribed providers increased the number of visits billed as LOS 4 or 5 by 1.3 percentage points (from 46.5% before implementation to 47.8%) (TABLE 2). Scribes were therefore associated with an additional 8.3 percentage points in LOS 4 or 5 billing (P < .001) (TABLE 2). This difference remained significant after adjusting for patient demographics (P < .001).

Continue to: Pay-for-performance quality measures

Breast cancer screening. Scribed providers increased the number of visits at which breast cancer screening was ordered by 2.7 percentage points (from 17.3% before implementation of scribes to 20.0%); during the same period, the number of visits at which breast cancer screening was ordered by nonscribed providers decreased by 1.9 percentage points (from 19.5% to 17.6%). Scribes were therefore associated with an increase of 4.6 percentage points in breast cancer screening orders, compared to nonscribed providers (P < .003) (TABLE 2). That difference remained significant after adjusting for patient demographics (P = .01).

Colon cancer screening. Similarly, scribed providers increased the number of visits at which colon cancer screening was ordered by 1.2 percentage points (from 19.2% before implementation of scribes to 20.3%); during the same period, the number of visits at which colon cancer screening was ordered by nonscribed providers decreased by 2.7 percentage points (from 18.5% to 15.9%) (P = .112). After adjusting for patient demographics, scribes were associated with an increase of 4.9 percentage points in colon cancer screening orders, compared to nonscribed providers (P = .044) (TABLE 2).

Cervical cancer screening. The rate at which cervical cancer screening was ordered did not change among scribed providers and decreased (by 2.5 percentage points) among nonscribed providers—a difference that was not statistically significant (P = .26).

Nonpreventive visits. Our findings overall did not change in analyses focused on nonpreventive visits, in which scribes were associated with an increase of 8.2 percentage points in LOS 4 or 5 billing (P < .001); an increase of 3.1 percentage points in HCC coding (P < .001); and an increase of 3.2 percentage points in breast cancer screening orders (P = .03) (TABLE 3). Although scribes were associated with an increase of 1.5 percentage points in cervical cancer screening orders and an increase of 3.1 percentage points in colon cancer screening orders, these increases did not reach statistical significance.

Discussion

We found that implementation of scribes is associated with (1) an increase in LOS coding and risk coding and (2) a higher frequency of addressing 2 of 3 pay-for-performance quality measures in primary care. In adjusted analyses in our study, and compared to nonscribed providers, scribes were associated with an additional 9.2 percentage points in LOS 4 or 5 billing; 3.6 percentage points in HCC coding; 4.0 percentage points in breast cancer screening orders; and 4.9 percentage points in colon cancer screening orders. Cervical cancer screening orders followed a similar pattern, with an increase of 2.3 percentage points in the adjusted screening order rate among scribed providers, compared to nonscribed providers, during implementation of scribes—although the increase was not significant. These findings did not change in analyses focused on nonpreventive visits.

Continue to: Our findings are consistent

Our findings are consistent with those of earlier studies. Prior examinations in ambulatory specialties found that scribes increased HCC coding,⁴ LOS billing,²⁴ and pay-for-performance metrics.¹⁸ The only study to examine these areas in primary care found that scribes were associated with increased pay-for-performance measure documentation,²⁰ a change that is necessary but insufficient to realize increased pay-for-­performance revenue. Therefore, our study confirms, for the first time, that PCPs can better address pay-for-performance measures, LOS billing, and HCC coding when working with a scribe in primary care.

Providers who used a scribe during the intervention period of our study increased the number of visits billed as LOS 4 or 5 by 9.6 percentage points.

Demands on primary care visits are increasing.²⁸ Physicians are required to provide more documentation; there is greater emphasis on PCPs meeting pay-for-­performance measures; and there are more data in the EMR to review. In this context, addressing pay-for-performance measures and gaps in risk coding is likely to be increasingly challenging. Our study suggests that scribes might provide a mechanism to increase risk coding, LOS billing, and pay-for-performance measures, despite increased demands on primary care visits.

Increase in LOS billing. In the settings in which we work, a fee-for-service LOS 4 primary care visit generates, on average, $20 to $75 more in revenue than an LOS 3 visit. Using an average of $50 additional revenue for LOS 4 billing, we estimate that a full-time scribe is associated with roughly $7,000 in additional revenue annually. We arrived at this estimate using an average of 1500 visits at LOS ≤ 3 for every PCP full-time equivalent. A 9.2 percentage–point increase in LOS 4 billing would lead to roughly 140 additional LOS 4 visits, with each visit generating an additional $50 in revenue.

This analysis does not account for increased revenue associated with increased pay for HCC coding identified in our study.

Our study also suggests that scribes might provide a mechanism to increase risk coding and payfor-performance, despite increased demands on primary care visits.

Furthermore, in our conservative assumption, the entire increase in LOS billing was from level 3 to level 4; in fact, a small percentage of that increase would be from level 2 and another small percentage would be to level 5—both of which would generate additional revenue. Our assumption therefore underestimates the full financial value associated with scribes in the absence of increased patient volume. Nonetheless, the assumption suggests that increases in LOS billing offset a substantial percentage of a scribe’s salary.

Continue to: Limitations of this study

Limitations of this study. Our study should be interpreted in the context of several limitations:

• The study was conducted at 1 institution. Our findings might not be generalizable beyond this setting.
• The study measures the impact of scribes when providers work with scribes part time. Because providers who utilize a scribe for all, or nearly all, their visits are likely to use a scribe more efficiently, our study might underestimate the full impact of a scribe.
• In some settings, team members such as medical assistants are trained to assist with documentation and other responsibilities (such as closing care gaps) in addition to other patient care responsibilities.^29-32 The extent to which our findings transfer to other models is unclear; studies comparing the impact of other models (which might provide even stronger outcomes) to the impact of medical scribes would be an interesting area for further research.
• In addition to the variability of models, there is likely variability in the quality and interactions of medical scribes, which might impact outcomes. We did not examine the qualities of scribes that led to outcomes in this study.
• We examined the impact of scribes on quality measure–ordering behaviors of providers, not on whether quality measures actually improved. Because scribes are associated with more face-to-face time with patients,²⁷ they might allow for increased attention being paid by physicians to barriers to pay-for-performance measures (eg, patient education). This could increase the likelihood that patients complete a multitude of screenings, and thus improve adherence and follow-up. However, the impact of scribes on quality measures is a topic for future study.

Value beyond volume. Any limitations notwithstanding, our study suggests that scribes are associated with financial benefit in addition to the benefit of increased volume. Primary care practices should therefore consider the financial benefit of scribes independent of their ability to add patient volume. By recognizing this additive value, primary care practices might more fully capture the benefit of scribes, which might then allow practices to employ scribes with less demand to increase volume. This added support without increased volume would, in turn, likely reduce provider burnout (and the costly associated turnover) and increase patient satisfaction, leading to a synergistic financial benefit.

CORRESPONDENCE
Wayne Altman, MD, FAAFP, Tufts University School of Medicine, 200 Harrison Avenue, Boston, MA 02111; wayne. [email protected]

ABSTRACT

Purpose Medical scribes are known to increase revenue by increasing visits to a medical practice. We examined whether medical scribes are associated with markers of financial benefit independent of increased visits.

Methods We conducted a pre- and post-­observational study with a control group, examining changes in the percentage of visits (1) coded as level of service 4 or 5, (2) with at least 1 hierarchical condition category code billed, and (3) at which orders for 3 pay-for-performance quality measures (screening for breast, cervical, and colon cancer) were placed, if due. We looked at changes in outcomes among scribed providers and compared them to nonscribed providers. We used generalized estimating equations with robust standard errors to account for repeated measures and the hierarchical nature of the data, controlling for patient demographics.

Results We examined 41,371 visits to 17 scribed providers and 230,297 visits to 78 nonscribed providers. In adjusted analyses, and compared to nonscribed providers, scribes were associated with an increase of:

• Frutiger LT Std9.2 percentage points in level-of-­service 4 or 5 billing (Frutiger LT StdP < .001)
• 3.6 percentage points in hierarchical condition category coding (Frutiger LT StdP < .001)
• 4.0 percentage points in breast cancer screening orders (Frutiger LT StdP = .01)
• 4.9 percentage points in colon cancer screening orders (Frutiger LT StdPFrutiger LT Std = .04).

Conclusions This study suggests that scribes are associated with financial benefit in addition to increased visit volume. Primary care practices should consider the financial benefit of scribes independent of their ability to add patient volume.

Increasingly, medical scribes are used in ambulatory care settings across the United States.¹ Scribes are trained personnel who accompany providers during visits to provide documentation support and assist with other administrative tasks. They are associated with reduced documentation time for providers^2-6 and improved provider satisfaction,^7-11 without detriment to^4-16 (or with possible improvement in^17-20) patient satisfaction in ambulatory care settings. At the same time, concerns remain that using scribes might inhibit patient communication, harm clinical reasoning, reduce the effectiveness of clinical decision-support tools, and simply serve as a work-around to fixing inefficiencies in the electronic medical record (EMR).^21-23

A driving force for the increased use of medical scribes is the expectation that they reduce the cost of providing care. Cost-­efficiency is typically described as resulting from a reduction in physician time per patient seen, which allows increased patient volume and, in turn, drives increased physician productivity.^{2,8,10,18,24-27} Whether scribes result in cost savings remains unclear; some papers suggest that scribes are cost efficient in ambulatory care,^2,10,18 while others have been unable to identify cost savings, particularly in primary care.⁴

One reason why scribes might not be associated with cost savings is that their financial benefit might be undercounted. Studies that focus on increased volume miss the opportunity to capture financial benefits conferred through mechanisms that are independent of seeing more patients:

• Scribes might help providers address and document more, and more complex, medical problems, allowing higher level-of-service (LOS) billing. For example, a provider chooses a lower LOS because they have insufficiently documented a visit to support a higher LOS; by assisting with documentation, the scribe might allow the provider to choose a higher LOS.
• Scribes might prompt a provider to use decision-support tools for risk coding (using appropriate medical codes to capture the patient’s level of medical complexity), thereby increasing reimbursement.
• Scribes might extend the time available during the visit for the provider to address pay-for-performance quality measures, such as cancer screening.

Continue to: Making visits count, not counting visits

Making visits count, not counting visits. In this study, we examined whether medical scribes in primary care are associated with improved markers of revenue that are independent of seeing more patients. Specifically, we examined whether scribes are associated with increased LOS coding, risk coding, and orders for pay-for-performance measures for all primary care visits and for nonpreventive primary care visits.

Methods

Design

This observational study compared the change in outcomes before implementation of scribes and during implementation of scribes, between scribed providers and nonscribed providers. We compared visits during the year prior to the implementation of scribes (July 2017–June 2018) with the year during their implementation (July 2018–2019).

The Cambridge Health Alliance Institutional Review Board considered this study exempt from review.

Setting

This study was conducted at a safety-net community academic health system that uses an EMR developed by Epic Systems [Verona, WI]. This EMR includes decision-support tools that prompt providers when pay-for-performance quality measures are due and when hierarchical condition category (HCC) codes—ie, specific diagnoses used by Medicare and other payers to reimburse providers for the complexity of their patients—might apply to the visit.

Primary care practices should consider the financial benefit of scribes, independent of their ability to add patient volume.

These EMR decision-support tools use algorithms that draw on age, gender, diagnoses that were billed previously or are on the problem list, laboratory findings, and prior imaging. They alert physicians when a patient is due for pay-for-performance quality measures, such as cancer screenings, and when HCC codes might be applicable.

Continue to: During the study period...

During the study period, the EMR ­decision-support tool for HCC coding underwent several changes designed to improve HCC coding. In addition, systematic changes to primary care visits took place, leading to an increase in the number of patients seen and screenings required.

Outcomes

We examined 2 categories of outcomes that confer financial benefit to many institutions: billing measures and pay-for-performance measures.

Billing measures included the percentage of visits (1) coded as LOS 4 or 5 and (2) with at least 1 HCC code billed (among those for which the decision-support tool identified at least 1 potential HCC code).

Pay-for-performance measures. We examined whether any of 3 pay-for-­performance quality measures were addressed during the visit, selecting 3 that are commonly addressed by primary care providers (PCPs) and that require PCPs to sign an order for screening during a primary care visit: breast cancer (mammography order), cervical cancer (Papanicolaou smear order), and colon cancer (an order for fecal occult blood testing or colonoscopy).

Intervention

Scribes were employees of Cambridge Health Alliance who had recently graduated from college and were interested in a career as a health care professional. Scribes received 3 days of training on how to function effectively in their role; 1 day of training in EMR functionality; and 2 hours of training on decision-support tools for pay-for-performance quality measures and risk coding. Scribes continued learning on the job through feedback from supervising PCPs. Scribes documented patient encounters, recording histories and findings on the physical exam and transcribing discussion of treatment plans and the PCP’s instructions to patients.

Continue to: The 14 scribes worked with 17 physician...

The 14 scribes worked with 17 physician and nurse practitioner PCPs beginning in July 2018. Participation by PCPs was voluntary; they received no compensation for participating in the scribe program. PCPs were not required to see additional patients to participate. PCPs who chose to work with a scribe were similar to those who declined a scribe, as regards gender, race, type of provider (MD or NP), tenure at the institution, and percentage of time in clinical work (see Table W-1).

The control group comprised providers who elected not to work with a scribe but who worked in the same clinics as the intervention providers.

Scribes might extend the time available during the visit for the provider to address pay-forperformance quality measures, such as cancer screening.

Scribes were assigned to a PCP based on availability during the PCP’s scheduled hours and worked with 1 PCP throughout the intervention (except for 1 PCP who worked with 2 scribes). All PCPs worked with their scribe(s) part time; on average, 49% of intervention PCPs’ visits were scribed.

Inclusion and exclusion criteria

Because the first year at an institution is a learning period for PCPs, we excluded those who worked at the institution for < 1 year before the start of the scribe program (n = 12). Based on the extensive clinical experience of 1 PCP (WA) with scribes, we excluded the first 200 visits or 6 weeks (whichever occurred first) with a scribe among all scribed providers, to account for an initial learning period (n = 2202, of 15,372 scribed visits [14%]). We also excluded 2 providers who left during the pre-intervention period or were in the intervention period for < 1 month.

To ensure that we captured visits to providers with clinically significant exposure to scribes, we required scribed providers to have ≥ 20% of their visits scribed during the intervention period. To minimize the potential for contamination, we excluded nonscribed visits to scribed providers during the intervention period (n = 2211), because such nonscribed visits were largely due to visits outside the scribe’s scheduled time.

Continue to: Analysis

We compared demographic characteristics for patients and providers using the chi-square test for categorical variables and the t test for continuous variables. We compared the change in outcomes from before implementation of scribes to during implementation of scribes among scribed providers, compared to nonscribed providers, using generalized estimating equations with robust standard errors to account for repeated measures (ie, multiple visits by the same patients) and the hierarchical nature of the data (ie, patients nested within providers). We then recalculated these estimates, controlling for patient demographics (age, gender, race, and ethnicity). We repeated these analyses for patients presenting for nonpreventive visits.

Results

Visit characteristics

We examined 271,768 visits, including 41,371 visits to 17 scribed providers and 230,397 visits to 78 nonscribed providers (Table 1). Patients were most likely to be female, > 21 years of age, have English as their language of care, and be non-White. Most visits were by established patients and were nonpreventive.

We noted no clinically significant differences in characteristics between visits with scribed providers and visits with nonscribed providers, and over time. Patient complexity measures, including care management enrollment and hospital admissions, were also similar between groups, and over time.

Billing measures

HCC coding. In 28.6% of visits, the decision-support tool identified at least 1 potential HCC code. Among these, the percentage of visits with at least 1 HCC code billed increased by 10.1 percentage points (from 3.9% before implementation of scribes to 14.0%) among scribed providers, compared to increasing by 6.5 percentage points (from 2.9% before implementation to 9.3%) among nonscribed providers (TABLE 2). Scribes were therefore associated with an additional 3.6 percentage-point increase in visits with at least 1 HCC code billed (P < .0001)—a difference that remained significant after adjusting for patient demographics (P < .0001).

LOS coding. Scribed providers increased the number of visits billed as LOS 4 or 5 by 9.6 percentage points (from 47.3% before implementation to 56.8%); during the same period, nonscribed providers increased the number of visits billed as LOS 4 or 5 by 1.3 percentage points (from 46.5% before implementation to 47.8%) (TABLE 2). Scribes were therefore associated with an additional 8.3 percentage points in LOS 4 or 5 billing (P < .001) (TABLE 2). This difference remained significant after adjusting for patient demographics (P < .001).

Continue to: Pay-for-performance quality measures

Breast cancer screening. Scribed providers increased the number of visits at which breast cancer screening was ordered by 2.7 percentage points (from 17.3% before implementation of scribes to 20.0%); during the same period, the number of visits at which breast cancer screening was ordered by nonscribed providers decreased by 1.9 percentage points (from 19.5% to 17.6%). Scribes were therefore associated with an increase of 4.6 percentage points in breast cancer screening orders, compared to nonscribed providers (P < .003) (TABLE 2). That difference remained significant after adjusting for patient demographics (P = .01).

Colon cancer screening. Similarly, scribed providers increased the number of visits at which colon cancer screening was ordered by 1.2 percentage points (from 19.2% before implementation of scribes to 20.3%); during the same period, the number of visits at which colon cancer screening was ordered by nonscribed providers decreased by 2.7 percentage points (from 18.5% to 15.9%) (P = .112). After adjusting for patient demographics, scribes were associated with an increase of 4.9 percentage points in colon cancer screening orders, compared to nonscribed providers (P = .044) (TABLE 2).

Cervical cancer screening. The rate at which cervical cancer screening was ordered did not change among scribed providers and decreased (by 2.5 percentage points) among nonscribed providers—a difference that was not statistically significant (P = .26).

Nonpreventive visits. Our findings overall did not change in analyses focused on nonpreventive visits, in which scribes were associated with an increase of 8.2 percentage points in LOS 4 or 5 billing (P < .001); an increase of 3.1 percentage points in HCC coding (P < .001); and an increase of 3.2 percentage points in breast cancer screening orders (P = .03) (TABLE 3). Although scribes were associated with an increase of 1.5 percentage points in cervical cancer screening orders and an increase of 3.1 percentage points in colon cancer screening orders, these increases did not reach statistical significance.

Discussion

We found that implementation of scribes is associated with (1) an increase in LOS coding and risk coding and (2) a higher frequency of addressing 2 of 3 pay-for-performance quality measures in primary care. In adjusted analyses in our study, and compared to nonscribed providers, scribes were associated with an additional 9.2 percentage points in LOS 4 or 5 billing; 3.6 percentage points in HCC coding; 4.0 percentage points in breast cancer screening orders; and 4.9 percentage points in colon cancer screening orders. Cervical cancer screening orders followed a similar pattern, with an increase of 2.3 percentage points in the adjusted screening order rate among scribed providers, compared to nonscribed providers, during implementation of scribes—although the increase was not significant. These findings did not change in analyses focused on nonpreventive visits.

Continue to: Our findings are consistent

Our findings are consistent with those of earlier studies. Prior examinations in ambulatory specialties found that scribes increased HCC coding,⁴ LOS billing,²⁴ and pay-for-performance metrics.¹⁸ The only study to examine these areas in primary care found that scribes were associated with increased pay-for-performance measure documentation,²⁰ a change that is necessary but insufficient to realize increased pay-for-­performance revenue. Therefore, our study confirms, for the first time, that PCPs can better address pay-for-performance measures, LOS billing, and HCC coding when working with a scribe in primary care.

Providers who used a scribe during the intervention period of our study increased the number of visits billed as LOS 4 or 5 by 9.6 percentage points.

Demands on primary care visits are increasing.²⁸ Physicians are required to provide more documentation; there is greater emphasis on PCPs meeting pay-for-­performance measures; and there are more data in the EMR to review. In this context, addressing pay-for-performance measures and gaps in risk coding is likely to be increasingly challenging. Our study suggests that scribes might provide a mechanism to increase risk coding, LOS billing, and pay-for-performance measures, despite increased demands on primary care visits.

Increase in LOS billing. In the settings in which we work, a fee-for-service LOS 4 primary care visit generates, on average, $20 to $75 more in revenue than an LOS 3 visit. Using an average of $50 additional revenue for LOS 4 billing, we estimate that a full-time scribe is associated with roughly $7,000 in additional revenue annually. We arrived at this estimate using an average of 1500 visits at LOS ≤ 3 for every PCP full-time equivalent. A 9.2 percentage–point increase in LOS 4 billing would lead to roughly 140 additional LOS 4 visits, with each visit generating an additional $50 in revenue.

This analysis does not account for increased revenue associated with increased pay for HCC coding identified in our study.

Our study also suggests that scribes might provide a mechanism to increase risk coding and payfor-performance, despite increased demands on primary care visits.

Furthermore, in our conservative assumption, the entire increase in LOS billing was from level 3 to level 4; in fact, a small percentage of that increase would be from level 2 and another small percentage would be to level 5—both of which would generate additional revenue. Our assumption therefore underestimates the full financial value associated with scribes in the absence of increased patient volume. Nonetheless, the assumption suggests that increases in LOS billing offset a substantial percentage of a scribe’s salary.

Continue to: Limitations of this study

Limitations of this study. Our study should be interpreted in the context of several limitations:

• The study was conducted at 1 institution. Our findings might not be generalizable beyond this setting.
• The study measures the impact of scribes when providers work with scribes part time. Because providers who utilize a scribe for all, or nearly all, their visits are likely to use a scribe more efficiently, our study might underestimate the full impact of a scribe.
• In some settings, team members such as medical assistants are trained to assist with documentation and other responsibilities (such as closing care gaps) in addition to other patient care responsibilities.^29-32 The extent to which our findings transfer to other models is unclear; studies comparing the impact of other models (which might provide even stronger outcomes) to the impact of medical scribes would be an interesting area for further research.
• In addition to the variability of models, there is likely variability in the quality and interactions of medical scribes, which might impact outcomes. We did not examine the qualities of scribes that led to outcomes in this study.
• We examined the impact of scribes on quality measure–ordering behaviors of providers, not on whether quality measures actually improved. Because scribes are associated with more face-to-face time with patients,²⁷ they might allow for increased attention being paid by physicians to barriers to pay-for-performance measures (eg, patient education). This could increase the likelihood that patients complete a multitude of screenings, and thus improve adherence and follow-up. However, the impact of scribes on quality measures is a topic for future study.

Value beyond volume. Any limitations notwithstanding, our study suggests that scribes are associated with financial benefit in addition to the benefit of increased volume. Primary care practices should therefore consider the financial benefit of scribes independent of their ability to add patient volume. By recognizing this additive value, primary care practices might more fully capture the benefit of scribes, which might then allow practices to employ scribes with less demand to increase volume. This added support without increased volume would, in turn, likely reduce provider burnout (and the costly associated turnover) and increase patient satisfaction, leading to a synergistic financial benefit.

CORRESPONDENCE
Wayne Altman, MD, FAAFP, Tufts University School of Medicine, 200 Harrison Avenue, Boston, MA 02111; wayne. [email protected]

“Vaccines have been the bright light of this extraordinary challenge that we’ve gone through,” said Anthony S. Fauci, MD, director of the National Institute of Allergy and Infectious Diseases.

In an address for the opening ceremony of the American Thoracic Society’s virtual international conference, Dr. Fauci emphasized the role of basic and clinical research and government support for science in helping turn the tide of the COVID-19 pandemic.

“A few weeks ago, I wrote an editorial in Science, because there was some misunderstanding about how and why we were able to go from a realization of a new pathogen in January of 2020, to getting doses of vaccines in the arms of individuals – a highly efficacious vaccine – 11 months later. Truly, an unprecedented accomplishment,” he said.

“But as I said in the editorial, the speed and efficiency with which these highly efficacious vaccines were developed, and their potential for saving millions of lives, are due to an extraordinary multidisciplinary effort, involving basic, preclinical, and clinical science that had been underway – out of the spotlight – for decades and decades before the unfolding of the COVID-19 pandemic, a fact that very few people really appreciate: namely, the importance of investment in biomedical research.”
 

The general addresses the troops

Perhaps no other audience is so well suited to receive Dr. Fauci’s speech as those who are currently attending (virtually) the ATS conference, including researchers who scrutinize the virus from every angle to describe its workings and identify its vulnerabilities, epidemiologists who study viral transmission and look for ways to thwart it, public health workers who fan out to communities across the country to push vaccine acceptance, and clinicians who specialize in critical care and pulmonary medicine, many of whom staff the respiratory floors and intensive care units where the most severely ill patients are treated.

Speaking about the lessons learned and challenges remaining from the COVID-19 pandemic, Dr. Fauci briefly reviewed the epidemiology, virology and transmission, diagnostics, and clinical course of SARS-CoV-2 infections and the therapeutics and vaccines for COVID-19.
 

Epidemiology

The pandemic began in December 2019 with recognition of a novel type of pneumonia in the Wuhan District of Central China, Dr. Fauci noted.

“Very quickly thereafter, in the first week of January 2020, the Chinese identified a new strain of coronavirus as [the] source of the outbreak. Fast forward to where we are right now: We have experienced and are experiencing the most devastating pandemic of a respiratory illness in the last 102 years, with already approximately 160 million individuals having been infected – and this is clearly a gross undercounting – and also 3.3 million deaths, again, very likely an undercounting,” he said.

According to the Centers for Disease Control and Prevention, as of May 9, 2021, there were approximately 32.5 million cases of COVID-19 and 578,520 deaths in the United States. Those cases and deaths occurred largely in three surges in the United States, in early spring, early summer, and late fall of 2020.
 

Virology and transmission

SARS-CoV-2 is a beta-coronavirus in the same subgenus as SARS-CoV-1 and some bat coronaviruses, Dr. Fauci explained. The viral genome is large, about 30,000 kilobases, and it has four structural proteins, most importantly the S or “spike” protein that allows the virus to attach to and fuse with cell membranes by binding to the ACE2 receptor on tissues in the upper and lower respiratory tract, gastrointestinal tract, cardiovascular system, and other organ systems.

The virus is transmitted mainly through exposure to respiratory droplets within 6 feet of an infected person, or sometimes through droplets or particles that remain in the air over time and various distances.

Contact with contaminated surfaces, once feared as a means of transmission, is now understood to be less common.

The virus has been detected in stool, blood, semen, and ocular secretions, although the role of transmission through these sources is still unknown.

“Some very interesting characteristics of this virus, really quite unique compared to other viruses, certainly other respiratory viruses, is [that] about a third to 40% of people who are infected never develop any symptoms,” Dr. Fauci said. “Importantly, and very problematic to what we do to contain it – particularly with regard to identification, isolation, and contract tracing – between 50% and 60% of the transmissions occur either from someone who will never develop symptoms, or someone in the presymptomatic phase of disease.”

The fundamentals of preventing acquisition and transmission are as familiar to most Americans now as the Pledge of Allegiance: universal mask wearing, physical distancing, avoiding crowds and congregate settings, preference for outdoor over indoor settings, and frequent hand washing, he noted.
 

Diagnostics

Tests for SARS-CoV-2 infection fall into three basic categories: molecular tests such as polymerase chain reaction (PCR) that are highly specific and highly sensitive for actual infections, antigen tests that detect the viral protein rather than the nucleic acids, and antibody tests to detect serum proteins made in response to viral infection.

Antigen testing is used largely for broader surveillance of groups of individuals to detect viral penetrance within that group, Dr. Fauci noted.
 

Clinical course

The clinical course of COVID-19 has some interesting characteristics but is not substantially different from a flu-like syndrome, Dr. Fauci said.

Symptoms and signs common to both types of infections include fever, cough, fatigue, anorexia, dyspnea, and myalgias, but the loss of smell and/or taste preceding the onset of respiratory symptoms is a unique feature of COVID-19.

Dr. Fauci cited data on more than 44,000 individuals with confirmed COVID-19 in China that showed that a large majority (81%) of cases were mild or moderate in nature, but 14% of patients experienced severe disease, and 5% were critically ill. The case-fatality rate in this study was 2.3%.

People at increased risk for severe disease include older adults and those of any age with certain comorbidities.

Manifestations of severe COVID-19 infections in adults can include neurological disorders, hyperinflammation, acute respiratory distress syndrome, cardiac dysfunction, hypercoagulability, and acute kidney injury.

In children, COVID-19 has been associated with a multisystem inflammatory syndrome (MIS-C) similar to Kawasaki disease.

In a substantial number of cases, the effects of COVID-19 can linger for 6 months or longer, Dr. Fauci said, pointing to a study from the University of Washington in Seattle.

Investigators there found that approximately 30% of patients enrolled at their center reported persistent symptoms for as long as 9 months after the initial illness, with fatigue as the most commonly reported symptom. One-third of outpatients with mild disease also reported persistent symptoms.
 

Therapeutics

Therapeutics that are either approved by the Food and Drug Administration, have emergency use authorization, or are in clinical trials for early or moderate disease include remdesivir (Veklury, Gilead Sciences), monoclonal antibodies, convalescent plasma, antiviral agents, hyperimmune globulin, anticoagulants, and immunomodulators.

Options for moderate to severe to advanced disease include dexamethasone, baricitinib (Olumiant, Eli Lilly and Company) plus remdesivir, and immunomodulators such as infliximab (Remicade, Janssen Biotech), and biosimilars.
 

Vaccines

Finally, Dr. Fauci reviewed the current state of vaccines, including the three with emergency use authorization from the FDA as of this writing: two nucleic acid, messenger RNA-based (mRNA) vaccines from Moderna and Pfizer/BioNTech, and an adenoviral vector-based vaccine from Johnson & Johnson.

Other vaccines in development or in use elsewhere in the world include recombinant protein and adjuvant approaches by GlaxoSmithKline and Sanofi (in a phase 2 clinical trial launched in February 2021) and by Novavax.

The three vaccines in use in the United States were highly efficacious in both clinical trials, with efficacy of about 95% for the mRNA vaccines and 67% for the Johnson & Johnson vaccine.

The real-world performance of these vaccines has been even more impressive, however.

For example, the Johnson & Johnson vaccine had 72% efficacy at preventing moderate to severe COVID 19 in the United States, 68% in Brazil, and 64% in South Africa, and 85% efficacy against severe disease across all regions studied, Dr. Fauci said.

He cited a study of 22,234 employees of the University of Texas Southwestern Medical Center in Dallas who were vaccinated under a program started on Dec. 15, 2020. The COVID-19 infection rate among these vaccinated employees was 0.05%.

Dr. Fauci recounted the experience in Israel, where the highly transmissible B.1.1.7 strain of SARS-CoV-2 is predominant. A chart of the progress shows clearly that as the vaccine doses delivered steadily increased, the number of COVID-19 cases began a precipitous decline.
 

Horse race

Fittingly for a speech presented on the day that the Preakness Stakes – the second leg in thoroughbred racing’s Triple Crown – was run, Dr. Fauci closed with a cartoon showing two racehorses, labeled “SARS-CoV-2” and “Vaccines,” nearly neck-and-neck, but with vaccines having a slight lead.

“We are in a race against the virus. The vaccines, and the virus: If we vaccinate the overwhelming proportion of our population, we will without a doubt be able to crush the outbreak in the same way as we have done with other viral-borne diseases like measles, smallpox, and polio.

“So, the message is: Get vaccinated,” he concluded.
 

“Vaccines have been the bright light of this extraordinary challenge that we’ve gone through,” said Anthony S. Fauci, MD, director of the National Institute of Allergy and Infectious Diseases.

In an address for the opening ceremony of the American Thoracic Society’s virtual international conference, Dr. Fauci emphasized the role of basic and clinical research and government support for science in helping turn the tide of the COVID-19 pandemic.

“A few weeks ago, I wrote an editorial in Science, because there was some misunderstanding about how and why we were able to go from a realization of a new pathogen in January of 2020, to getting doses of vaccines in the arms of individuals – a highly efficacious vaccine – 11 months later. Truly, an unprecedented accomplishment,” he said.

“But as I said in the editorial, the speed and efficiency with which these highly efficacious vaccines were developed, and their potential for saving millions of lives, are due to an extraordinary multidisciplinary effort, involving basic, preclinical, and clinical science that had been underway – out of the spotlight – for decades and decades before the unfolding of the COVID-19 pandemic, a fact that very few people really appreciate: namely, the importance of investment in biomedical research.”
 

The general addresses the troops

Perhaps no other audience is so well suited to receive Dr. Fauci’s speech as those who are currently attending (virtually) the ATS conference, including researchers who scrutinize the virus from every angle to describe its workings and identify its vulnerabilities, epidemiologists who study viral transmission and look for ways to thwart it, public health workers who fan out to communities across the country to push vaccine acceptance, and clinicians who specialize in critical care and pulmonary medicine, many of whom staff the respiratory floors and intensive care units where the most severely ill patients are treated.

Speaking about the lessons learned and challenges remaining from the COVID-19 pandemic, Dr. Fauci briefly reviewed the epidemiology, virology and transmission, diagnostics, and clinical course of SARS-CoV-2 infections and the therapeutics and vaccines for COVID-19.
 

Epidemiology

The pandemic began in December 2019 with recognition of a novel type of pneumonia in the Wuhan District of Central China, Dr. Fauci noted.

“Very quickly thereafter, in the first week of January 2020, the Chinese identified a new strain of coronavirus as [the] source of the outbreak. Fast forward to where we are right now: We have experienced and are experiencing the most devastating pandemic of a respiratory illness in the last 102 years, with already approximately 160 million individuals having been infected – and this is clearly a gross undercounting – and also 3.3 million deaths, again, very likely an undercounting,” he said.

According to the Centers for Disease Control and Prevention, as of May 9, 2021, there were approximately 32.5 million cases of COVID-19 and 578,520 deaths in the United States. Those cases and deaths occurred largely in three surges in the United States, in early spring, early summer, and late fall of 2020.
 

Virology and transmission

SARS-CoV-2 is a beta-coronavirus in the same subgenus as SARS-CoV-1 and some bat coronaviruses, Dr. Fauci explained. The viral genome is large, about 30,000 kilobases, and it has four structural proteins, most importantly the S or “spike” protein that allows the virus to attach to and fuse with cell membranes by binding to the ACE2 receptor on tissues in the upper and lower respiratory tract, gastrointestinal tract, cardiovascular system, and other organ systems.

The virus is transmitted mainly through exposure to respiratory droplets within 6 feet of an infected person, or sometimes through droplets or particles that remain in the air over time and various distances.

Contact with contaminated surfaces, once feared as a means of transmission, is now understood to be less common.

The virus has been detected in stool, blood, semen, and ocular secretions, although the role of transmission through these sources is still unknown.

“Some very interesting characteristics of this virus, really quite unique compared to other viruses, certainly other respiratory viruses, is [that] about a third to 40% of people who are infected never develop any symptoms,” Dr. Fauci said. “Importantly, and very problematic to what we do to contain it – particularly with regard to identification, isolation, and contract tracing – between 50% and 60% of the transmissions occur either from someone who will never develop symptoms, or someone in the presymptomatic phase of disease.”

The fundamentals of preventing acquisition and transmission are as familiar to most Americans now as the Pledge of Allegiance: universal mask wearing, physical distancing, avoiding crowds and congregate settings, preference for outdoor over indoor settings, and frequent hand washing, he noted.
 

Diagnostics

Tests for SARS-CoV-2 infection fall into three basic categories: molecular tests such as polymerase chain reaction (PCR) that are highly specific and highly sensitive for actual infections, antigen tests that detect the viral protein rather than the nucleic acids, and antibody tests to detect serum proteins made in response to viral infection.

Antigen testing is used largely for broader surveillance of groups of individuals to detect viral penetrance within that group, Dr. Fauci noted.
 

Clinical course

The clinical course of COVID-19 has some interesting characteristics but is not substantially different from a flu-like syndrome, Dr. Fauci said.

Symptoms and signs common to both types of infections include fever, cough, fatigue, anorexia, dyspnea, and myalgias, but the loss of smell and/or taste preceding the onset of respiratory symptoms is a unique feature of COVID-19.

Dr. Fauci cited data on more than 44,000 individuals with confirmed COVID-19 in China that showed that a large majority (81%) of cases were mild or moderate in nature, but 14% of patients experienced severe disease, and 5% were critically ill. The case-fatality rate in this study was 2.3%.

People at increased risk for severe disease include older adults and those of any age with certain comorbidities.

Manifestations of severe COVID-19 infections in adults can include neurological disorders, hyperinflammation, acute respiratory distress syndrome, cardiac dysfunction, hypercoagulability, and acute kidney injury.

In children, COVID-19 has been associated with a multisystem inflammatory syndrome (MIS-C) similar to Kawasaki disease.

In a substantial number of cases, the effects of COVID-19 can linger for 6 months or longer, Dr. Fauci said, pointing to a study from the University of Washington in Seattle.

Investigators there found that approximately 30% of patients enrolled at their center reported persistent symptoms for as long as 9 months after the initial illness, with fatigue as the most commonly reported symptom. One-third of outpatients with mild disease also reported persistent symptoms.
 

Therapeutics

Therapeutics that are either approved by the Food and Drug Administration, have emergency use authorization, or are in clinical trials for early or moderate disease include remdesivir (Veklury, Gilead Sciences), monoclonal antibodies, convalescent plasma, antiviral agents, hyperimmune globulin, anticoagulants, and immunomodulators.

Options for moderate to severe to advanced disease include dexamethasone, baricitinib (Olumiant, Eli Lilly and Company) plus remdesivir, and immunomodulators such as infliximab (Remicade, Janssen Biotech), and biosimilars.
 

Vaccines

Finally, Dr. Fauci reviewed the current state of vaccines, including the three with emergency use authorization from the FDA as of this writing: two nucleic acid, messenger RNA-based (mRNA) vaccines from Moderna and Pfizer/BioNTech, and an adenoviral vector-based vaccine from Johnson & Johnson.

Other vaccines in development or in use elsewhere in the world include recombinant protein and adjuvant approaches by GlaxoSmithKline and Sanofi (in a phase 2 clinical trial launched in February 2021) and by Novavax.

The three vaccines in use in the United States were highly efficacious in both clinical trials, with efficacy of about 95% for the mRNA vaccines and 67% for the Johnson & Johnson vaccine.

The real-world performance of these vaccines has been even more impressive, however.

For example, the Johnson & Johnson vaccine had 72% efficacy at preventing moderate to severe COVID 19 in the United States, 68% in Brazil, and 64% in South Africa, and 85% efficacy against severe disease across all regions studied, Dr. Fauci said.

He cited a study of 22,234 employees of the University of Texas Southwestern Medical Center in Dallas who were vaccinated under a program started on Dec. 15, 2020. The COVID-19 infection rate among these vaccinated employees was 0.05%.

Dr. Fauci recounted the experience in Israel, where the highly transmissible B.1.1.7 strain of SARS-CoV-2 is predominant. A chart of the progress shows clearly that as the vaccine doses delivered steadily increased, the number of COVID-19 cases began a precipitous decline.
 

Horse race

Fittingly for a speech presented on the day that the Preakness Stakes – the second leg in thoroughbred racing’s Triple Crown – was run, Dr. Fauci closed with a cartoon showing two racehorses, labeled “SARS-CoV-2” and “Vaccines,” nearly neck-and-neck, but with vaccines having a slight lead.

“We are in a race against the virus. The vaccines, and the virus: If we vaccinate the overwhelming proportion of our population, we will without a doubt be able to crush the outbreak in the same way as we have done with other viral-borne diseases like measles, smallpox, and polio.

“So, the message is: Get vaccinated,” he concluded.
 

“Vaccines have been the bright light of this extraordinary challenge that we’ve gone through,” said Anthony S. Fauci, MD, director of the National Institute of Allergy and Infectious Diseases.

In an address for the opening ceremony of the American Thoracic Society’s virtual international conference, Dr. Fauci emphasized the role of basic and clinical research and government support for science in helping turn the tide of the COVID-19 pandemic.

“A few weeks ago, I wrote an editorial in Science, because there was some misunderstanding about how and why we were able to go from a realization of a new pathogen in January of 2020, to getting doses of vaccines in the arms of individuals – a highly efficacious vaccine – 11 months later. Truly, an unprecedented accomplishment,” he said.

“But as I said in the editorial, the speed and efficiency with which these highly efficacious vaccines were developed, and their potential for saving millions of lives, are due to an extraordinary multidisciplinary effort, involving basic, preclinical, and clinical science that had been underway – out of the spotlight – for decades and decades before the unfolding of the COVID-19 pandemic, a fact that very few people really appreciate: namely, the importance of investment in biomedical research.”
 

The general addresses the troops

Perhaps no other audience is so well suited to receive Dr. Fauci’s speech as those who are currently attending (virtually) the ATS conference, including researchers who scrutinize the virus from every angle to describe its workings and identify its vulnerabilities, epidemiologists who study viral transmission and look for ways to thwart it, public health workers who fan out to communities across the country to push vaccine acceptance, and clinicians who specialize in critical care and pulmonary medicine, many of whom staff the respiratory floors and intensive care units where the most severely ill patients are treated.

Speaking about the lessons learned and challenges remaining from the COVID-19 pandemic, Dr. Fauci briefly reviewed the epidemiology, virology and transmission, diagnostics, and clinical course of SARS-CoV-2 infections and the therapeutics and vaccines for COVID-19.
 

Epidemiology

The pandemic began in December 2019 with recognition of a novel type of pneumonia in the Wuhan District of Central China, Dr. Fauci noted.

“Very quickly thereafter, in the first week of January 2020, the Chinese identified a new strain of coronavirus as [the] source of the outbreak. Fast forward to where we are right now: We have experienced and are experiencing the most devastating pandemic of a respiratory illness in the last 102 years, with already approximately 160 million individuals having been infected – and this is clearly a gross undercounting – and also 3.3 million deaths, again, very likely an undercounting,” he said.

According to the Centers for Disease Control and Prevention, as of May 9, 2021, there were approximately 32.5 million cases of COVID-19 and 578,520 deaths in the United States. Those cases and deaths occurred largely in three surges in the United States, in early spring, early summer, and late fall of 2020.
 

Virology and transmission

SARS-CoV-2 is a beta-coronavirus in the same subgenus as SARS-CoV-1 and some bat coronaviruses, Dr. Fauci explained. The viral genome is large, about 30,000 kilobases, and it has four structural proteins, most importantly the S or “spike” protein that allows the virus to attach to and fuse with cell membranes by binding to the ACE2 receptor on tissues in the upper and lower respiratory tract, gastrointestinal tract, cardiovascular system, and other organ systems.

The virus is transmitted mainly through exposure to respiratory droplets within 6 feet of an infected person, or sometimes through droplets or particles that remain in the air over time and various distances.

Contact with contaminated surfaces, once feared as a means of transmission, is now understood to be less common.

The virus has been detected in stool, blood, semen, and ocular secretions, although the role of transmission through these sources is still unknown.

“Some very interesting characteristics of this virus, really quite unique compared to other viruses, certainly other respiratory viruses, is [that] about a third to 40% of people who are infected never develop any symptoms,” Dr. Fauci said. “Importantly, and very problematic to what we do to contain it – particularly with regard to identification, isolation, and contract tracing – between 50% and 60% of the transmissions occur either from someone who will never develop symptoms, or someone in the presymptomatic phase of disease.”

The fundamentals of preventing acquisition and transmission are as familiar to most Americans now as the Pledge of Allegiance: universal mask wearing, physical distancing, avoiding crowds and congregate settings, preference for outdoor over indoor settings, and frequent hand washing, he noted.
 

Diagnostics

Tests for SARS-CoV-2 infection fall into three basic categories: molecular tests such as polymerase chain reaction (PCR) that are highly specific and highly sensitive for actual infections, antigen tests that detect the viral protein rather than the nucleic acids, and antibody tests to detect serum proteins made in response to viral infection.

Antigen testing is used largely for broader surveillance of groups of individuals to detect viral penetrance within that group, Dr. Fauci noted.
 

Clinical course

The clinical course of COVID-19 has some interesting characteristics but is not substantially different from a flu-like syndrome, Dr. Fauci said.

Symptoms and signs common to both types of infections include fever, cough, fatigue, anorexia, dyspnea, and myalgias, but the loss of smell and/or taste preceding the onset of respiratory symptoms is a unique feature of COVID-19.

Dr. Fauci cited data on more than 44,000 individuals with confirmed COVID-19 in China that showed that a large majority (81%) of cases were mild or moderate in nature, but 14% of patients experienced severe disease, and 5% were critically ill. The case-fatality rate in this study was 2.3%.

People at increased risk for severe disease include older adults and those of any age with certain comorbidities.

Manifestations of severe COVID-19 infections in adults can include neurological disorders, hyperinflammation, acute respiratory distress syndrome, cardiac dysfunction, hypercoagulability, and acute kidney injury.

In children, COVID-19 has been associated with a multisystem inflammatory syndrome (MIS-C) similar to Kawasaki disease.

In a substantial number of cases, the effects of COVID-19 can linger for 6 months or longer, Dr. Fauci said, pointing to a study from the University of Washington in Seattle.

Investigators there found that approximately 30% of patients enrolled at their center reported persistent symptoms for as long as 9 months after the initial illness, with fatigue as the most commonly reported symptom. One-third of outpatients with mild disease also reported persistent symptoms.
 

Therapeutics

Therapeutics that are either approved by the Food and Drug Administration, have emergency use authorization, or are in clinical trials for early or moderate disease include remdesivir (Veklury, Gilead Sciences), monoclonal antibodies, convalescent plasma, antiviral agents, hyperimmune globulin, anticoagulants, and immunomodulators.

Options for moderate to severe to advanced disease include dexamethasone, baricitinib (Olumiant, Eli Lilly and Company) plus remdesivir, and immunomodulators such as infliximab (Remicade, Janssen Biotech), and biosimilars.
 

Vaccines

Finally, Dr. Fauci reviewed the current state of vaccines, including the three with emergency use authorization from the FDA as of this writing: two nucleic acid, messenger RNA-based (mRNA) vaccines from Moderna and Pfizer/BioNTech, and an adenoviral vector-based vaccine from Johnson & Johnson.

Other vaccines in development or in use elsewhere in the world include recombinant protein and adjuvant approaches by GlaxoSmithKline and Sanofi (in a phase 2 clinical trial launched in February 2021) and by Novavax.

The three vaccines in use in the United States were highly efficacious in both clinical trials, with efficacy of about 95% for the mRNA vaccines and 67% for the Johnson & Johnson vaccine.

The real-world performance of these vaccines has been even more impressive, however.

For example, the Johnson & Johnson vaccine had 72% efficacy at preventing moderate to severe COVID 19 in the United States, 68% in Brazil, and 64% in South Africa, and 85% efficacy against severe disease across all regions studied, Dr. Fauci said.

He cited a study of 22,234 employees of the University of Texas Southwestern Medical Center in Dallas who were vaccinated under a program started on Dec. 15, 2020. The COVID-19 infection rate among these vaccinated employees was 0.05%.

Dr. Fauci recounted the experience in Israel, where the highly transmissible B.1.1.7 strain of SARS-CoV-2 is predominant. A chart of the progress shows clearly that as the vaccine doses delivered steadily increased, the number of COVID-19 cases began a precipitous decline.
 

Horse race

Fittingly for a speech presented on the day that the Preakness Stakes – the second leg in thoroughbred racing’s Triple Crown – was run, Dr. Fauci closed with a cartoon showing two racehorses, labeled “SARS-CoV-2” and “Vaccines,” nearly neck-and-neck, but with vaccines having a slight lead.

“We are in a race against the virus. The vaccines, and the virus: If we vaccinate the overwhelming proportion of our population, we will without a doubt be able to crush the outbreak in the same way as we have done with other viral-borne diseases like measles, smallpox, and polio.

“So, the message is: Get vaccinated,” he concluded.
 

Physicians in several specialties continue to see sharp drops in patient visits, but for internists, the numbers have rebounded since the beginning of the pandemic.

Internists are seeing only 3% fewer patients than they did before the COVID-19 pandemic (72 per week on average now vs. 74 before the pandemic). Comparatively, for pediatricians, patient volume remains down 18%. Dermatologists, otolaryngologists, and orthopedists report that visits are down by about 15%.

The number of hours worked also rebounded for internists. In fact, some report working slightly more hours now than they did before the pandemic (52 hours a week, up from 50).

Pay for internists continues to hover near the bottom of the scale among specialties. In this year’s Medscape Internist Compensation Report 2021, internists averaged $248,000, down from $251,000 last year. Pediatricians were the lowest paid, at $221,000, followed by family physicians, at $236,000. Plastic surgeons made the most, at $526,000, followed by orthopedists, at $511,000.

It helped to be self-employed. These internists made $276,000 on average, compared with $238,000 for their employed counterparts.
 

Half say pay is fair

Internists are also near the bottom among specialists who feel they are fairly compensated. As in last year’s survey, just more than half of internists (52%) said they felt that they were fairly paid this year. By comparison, 79% of oncologists reported they were fairly compensated, which is on the high end regarding satisfaction, but only 44% of infectious diseases specialists felt that way.

Some indicators in the survey responses may help explain the dissatisfaction.

Internists are near the top in time spent on paperwork. On average, they spent 19.7 hours on paperwork and administration this year, up slightly from 18.5 last year. Infectious disease physicians spent the most time on those tasks (24.2 hours a week), and anesthesiologists spent the fewest, at 10.1 hours per week.

Administrative work was among many frustrations internists reported. The following are the top five most challenging aspects of the job, according to the respondents:

• Having so many rules and regulations (24%)
• Having to work long hours (16%)
• Dealing with difficult patients (16%)
• Working with electronic health records systems (11%)
• Danger/risk associated with treating COVID-19 patients (10%)

Conversely, the most rewarding aspects were “gratitude/relationships with patients” (31%); “knowing that I’m making the world a better place” (26%); and “being very good at what I do” (20%).
 

More than one-third lost income

More than one-third of internists (36%) reported that they lost some income during the past year.

Among those who lost income, 81% said they expect income to return to prepandemic levels within 3 years. Half of that group expected the rebound would come within the next year.

Slightly more than one-third of internists said they would participate in the merit-based incentive payment system (MIPS), and 12% said they would participate in advanced alternative payment models. The rest either said they would participate in neither, or they hadn’t decided.

“The stakes for the Quality Payment Program – the program that incorporates MIPS – are high, with a 9% penalty applied to all Medicare reimbursement for failure to participate,” says Elizabeth Woodcock, MBA, CPC, president of the physician practice consulting firm Woodcock and Associates, in Atlanta, Georgia.

“With margins already slim,” she told this news organization, “most physicians can’t afford this massive penalty.”

If they could choose again, most internists (76%) said they would choose medicine, which was almost the same number as physicians overall who would pick medicine again. Oncologists (88%) and ophthalmologists (87%) were the specialists most likely to choose medicine again. Those in physical medicine and rehabilitation were least likely to choose medicine again, at 67%.

But asked about their specialty, internists’ enthusiasm decreased. Only 68% said that they would make that same choice again.

That was up considerably, however, from the 2015 survey: For that year, only 25% said they would choose internal medicine again.

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

Physicians in several specialties continue to see sharp drops in patient visits, but for internists, the numbers have rebounded since the beginning of the pandemic.

Internists are seeing only 3% fewer patients than they did before the COVID-19 pandemic (72 per week on average now vs. 74 before the pandemic). Comparatively, for pediatricians, patient volume remains down 18%. Dermatologists, otolaryngologists, and orthopedists report that visits are down by about 15%.

The number of hours worked also rebounded for internists. In fact, some report working slightly more hours now than they did before the pandemic (52 hours a week, up from 50).

Pay for internists continues to hover near the bottom of the scale among specialties. In this year’s Medscape Internist Compensation Report 2021, internists averaged $248,000, down from $251,000 last year. Pediatricians were the lowest paid, at $221,000, followed by family physicians, at $236,000. Plastic surgeons made the most, at $526,000, followed by orthopedists, at $511,000.

It helped to be self-employed. These internists made $276,000 on average, compared with $238,000 for their employed counterparts.
 

Half say pay is fair

Internists are also near the bottom among specialists who feel they are fairly compensated. As in last year’s survey, just more than half of internists (52%) said they felt that they were fairly paid this year. By comparison, 79% of oncologists reported they were fairly compensated, which is on the high end regarding satisfaction, but only 44% of infectious diseases specialists felt that way.

Some indicators in the survey responses may help explain the dissatisfaction.

Internists are near the top in time spent on paperwork. On average, they spent 19.7 hours on paperwork and administration this year, up slightly from 18.5 last year. Infectious disease physicians spent the most time on those tasks (24.2 hours a week), and anesthesiologists spent the fewest, at 10.1 hours per week.

Administrative work was among many frustrations internists reported. The following are the top five most challenging aspects of the job, according to the respondents:

• Having so many rules and regulations (24%)
• Having to work long hours (16%)
• Dealing with difficult patients (16%)
• Working with electronic health records systems (11%)
• Danger/risk associated with treating COVID-19 patients (10%)

Conversely, the most rewarding aspects were “gratitude/relationships with patients” (31%); “knowing that I’m making the world a better place” (26%); and “being very good at what I do” (20%).
 

More than one-third lost income

More than one-third of internists (36%) reported that they lost some income during the past year.

Among those who lost income, 81% said they expect income to return to prepandemic levels within 3 years. Half of that group expected the rebound would come within the next year.

Slightly more than one-third of internists said they would participate in the merit-based incentive payment system (MIPS), and 12% said they would participate in advanced alternative payment models. The rest either said they would participate in neither, or they hadn’t decided.

“The stakes for the Quality Payment Program – the program that incorporates MIPS – are high, with a 9% penalty applied to all Medicare reimbursement for failure to participate,” says Elizabeth Woodcock, MBA, CPC, president of the physician practice consulting firm Woodcock and Associates, in Atlanta, Georgia.

“With margins already slim,” she told this news organization, “most physicians can’t afford this massive penalty.”

If they could choose again, most internists (76%) said they would choose medicine, which was almost the same number as physicians overall who would pick medicine again. Oncologists (88%) and ophthalmologists (87%) were the specialists most likely to choose medicine again. Those in physical medicine and rehabilitation were least likely to choose medicine again, at 67%.

But asked about their specialty, internists’ enthusiasm decreased. Only 68% said that they would make that same choice again.

That was up considerably, however, from the 2015 survey: For that year, only 25% said they would choose internal medicine again.

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

Physicians in several specialties continue to see sharp drops in patient visits, but for internists, the numbers have rebounded since the beginning of the pandemic.

Internists are seeing only 3% fewer patients than they did before the COVID-19 pandemic (72 per week on average now vs. 74 before the pandemic). Comparatively, for pediatricians, patient volume remains down 18%. Dermatologists, otolaryngologists, and orthopedists report that visits are down by about 15%.

The number of hours worked also rebounded for internists. In fact, some report working slightly more hours now than they did before the pandemic (52 hours a week, up from 50).

Pay for internists continues to hover near the bottom of the scale among specialties. In this year’s Medscape Internist Compensation Report 2021, internists averaged $248,000, down from $251,000 last year. Pediatricians were the lowest paid, at $221,000, followed by family physicians, at $236,000. Plastic surgeons made the most, at $526,000, followed by orthopedists, at $511,000.

It helped to be self-employed. These internists made $276,000 on average, compared with $238,000 for their employed counterparts.
 

Half say pay is fair

Internists are also near the bottom among specialists who feel they are fairly compensated. As in last year’s survey, just more than half of internists (52%) said they felt that they were fairly paid this year. By comparison, 79% of oncologists reported they were fairly compensated, which is on the high end regarding satisfaction, but only 44% of infectious diseases specialists felt that way.

Some indicators in the survey responses may help explain the dissatisfaction.

Internists are near the top in time spent on paperwork. On average, they spent 19.7 hours on paperwork and administration this year, up slightly from 18.5 last year. Infectious disease physicians spent the most time on those tasks (24.2 hours a week), and anesthesiologists spent the fewest, at 10.1 hours per week.

Administrative work was among many frustrations internists reported. The following are the top five most challenging aspects of the job, according to the respondents:

• Having so many rules and regulations (24%)
• Having to work long hours (16%)
• Dealing with difficult patients (16%)
• Working with electronic health records systems (11%)
• Danger/risk associated with treating COVID-19 patients (10%)

Conversely, the most rewarding aspects were “gratitude/relationships with patients” (31%); “knowing that I’m making the world a better place” (26%); and “being very good at what I do” (20%).
 

More than one-third lost income

More than one-third of internists (36%) reported that they lost some income during the past year.

Among those who lost income, 81% said they expect income to return to prepandemic levels within 3 years. Half of that group expected the rebound would come within the next year.

Slightly more than one-third of internists said they would participate in the merit-based incentive payment system (MIPS), and 12% said they would participate in advanced alternative payment models. The rest either said they would participate in neither, or they hadn’t decided.

“The stakes for the Quality Payment Program – the program that incorporates MIPS – are high, with a 9% penalty applied to all Medicare reimbursement for failure to participate,” says Elizabeth Woodcock, MBA, CPC, president of the physician practice consulting firm Woodcock and Associates, in Atlanta, Georgia.

“With margins already slim,” she told this news organization, “most physicians can’t afford this massive penalty.”

If they could choose again, most internists (76%) said they would choose medicine, which was almost the same number as physicians overall who would pick medicine again. Oncologists (88%) and ophthalmologists (87%) were the specialists most likely to choose medicine again. Those in physical medicine and rehabilitation were least likely to choose medicine again, at 67%.

But asked about their specialty, internists’ enthusiasm decreased. Only 68% said that they would make that same choice again.

That was up considerably, however, from the 2015 survey: For that year, only 25% said they would choose internal medicine again.

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

Perimenopausal women are using prescription sleep medications for long periods of time despite no evidence of efficacy, a new study shows.

“While there are good data from [randomized, controlled trials] that these medications improve sleep disturbances in the short term,” few studies have examined whether they provide long-term benefits, stated the authors of the paper, which was published in BMJ Open.

“The current observational study does not support use of sleep medications over the long term, as there were no self-reported differences at 1 or 2 years of follow-up comparing sleep medication users with nonusers,” author Daniel H. Solomon, MD, MPH, from Brigham and Women’s Hospital, Boston, and colleagues wrote.

Women included in the analysis were drawn from the Study of Women’s Health Across the Nation (SWAN), an ongoing multicenter, longitudinal study examining women during the menopausal transition. The average age of the women included in the cohort was 49.5 years and approximately half were White. All women reported a sleep disturbance on at least 3 nights per week during a 2-week interval. At follow up, women were asked to use a Likert scale to rate three aspects of sleep: difficulty initiating sleep, frequent awakening, and waking up early. On the scale, 1 represented having no difficulties on any nights, 3 represented having difficulties 1-2 nights per week, and 5 represented having difficulty 5-7 nights per week.

Women already using prescription sleep medication at their baseline visit were excluded from the study. Medications used included benzodiazepines, selective BZD receptor agonists, and other hypnotics.

Over the 21 years of follow-up in the SWAN study (1995-2016), Dr. Solomon and colleagues identified 238 women using sleep medication and these were compared with a cohort of 447 propensity score–matched non–sleep medication uses. Overall, the 685 women included were similar in characteristics to each other as well as to the other potentially eligible women not included in the analysis.
 

Sleep disturbance patterns compared

At baseline, sleep disturbance patterns were similar between the two groups. Among medication users, the mean score for difficulty initiating sleep was 2.7 (95% confidence interval, 2.5-2.9), waking frequently 3.8 (95% CI, 3.6-3.9), and waking early 2.9 (95% CI, 2.7-3.1). Among the nonusers, the baseline scores were 2.6 (95% CI, 2.5-2.7), 3.7 (95% CI, 3.6-3.8), and 2.7 (95% CI, 2.5-2.8), respectively. After 1 year, there was no statistically significant difference in scores between the two groups. The average ratings for medication users were 2.6 (95% CI, 2.3-2.8) for difficulty initiating sleep, 3.8 (95% CI, 3.6-4.0) for waking frequently, and 2.8 (95% CI, 2.6-3.0) for waking early.

Average ratings among nonusers were 2.3 (95% CI, 2.2-2.4), 3.5 (95% CI, 3.3-3.6), and 2.5 (95% CI, 2.3-2.6), respectively.

After 2 years, there were still no statistically significant reductions in sleep disturbances among those taking prescription sleep medications, compared with those not taking medication.

The researchers noted that approximately half of the women in this cohort were current or past tobacco users and that 20% were moderate to heavy alcohol users.
 

More work-up, not more medication, needed

The study authors acknowledged the limitations of an observational study and noted that, since participants only reported medication use and sleep disturbances at annual visits, they did not know whether patients’ medication use was intermittent or of any interim outcomes. Additionally, the authors pointed out that those classified as “nonusers” may have been using over-the-counter medication.

“Investigations should look at detailed-use patterns, on a daily or weekly basis, with frequent outcomes data,” Dr. Solomon said in an interview. “While our data shed new light on chronic use, we only had data collected on an annual basis; daily or weekly data would provide more granular information.”

Regarding clinician prescribing practices, Dr. Solomon said, “short-term, intermittent use can be helpful, but use these agents sparingly” and “educate patients that chronic regular use of medications for sleep is not associated with improvement in sleep disturbances.”

Commenting on the study, Andrea Matsumura, MD, a sleep specialist at the Oregon Clinic in Portland, echoed this sentiment: “When someone says they are having trouble sleeping this is the tip of the iceberg and it warrants an evaluation to determine if someone has a breathing disorder, a circadian disorder, a life situation, or a type of insomnia that is driving the sleeplessness.”

“I think this study supports what we all should know,” Dr. Matsumura concluded. “Sleep aids are not meant to be used long term” and should not be used for longer than 2 weeks without further work-up.

Funding for this study was provided through a grant from the National Institutes of Health. Dr. Solomon has received salary support from research grants to Brigham and Women’s Hospital for unrelated work from AbbVie, Amgen, Corrona, Genentech and Pfizer. The other authors and Dr. Matsumura have reported no relevant financial relationships.

Perimenopausal women are using prescription sleep medications for long periods of time despite no evidence of efficacy, a new study shows.

“While there are good data from [randomized, controlled trials] that these medications improve sleep disturbances in the short term,” few studies have examined whether they provide long-term benefits, stated the authors of the paper, which was published in BMJ Open.

“The current observational study does not support use of sleep medications over the long term, as there were no self-reported differences at 1 or 2 years of follow-up comparing sleep medication users with nonusers,” author Daniel H. Solomon, MD, MPH, from Brigham and Women’s Hospital, Boston, and colleagues wrote.

Women included in the analysis were drawn from the Study of Women’s Health Across the Nation (SWAN), an ongoing multicenter, longitudinal study examining women during the menopausal transition. The average age of the women included in the cohort was 49.5 years and approximately half were White. All women reported a sleep disturbance on at least 3 nights per week during a 2-week interval. At follow up, women were asked to use a Likert scale to rate three aspects of sleep: difficulty initiating sleep, frequent awakening, and waking up early. On the scale, 1 represented having no difficulties on any nights, 3 represented having difficulties 1-2 nights per week, and 5 represented having difficulty 5-7 nights per week.

Women already using prescription sleep medication at their baseline visit were excluded from the study. Medications used included benzodiazepines, selective BZD receptor agonists, and other hypnotics.

Over the 21 years of follow-up in the SWAN study (1995-2016), Dr. Solomon and colleagues identified 238 women using sleep medication and these were compared with a cohort of 447 propensity score–matched non–sleep medication uses. Overall, the 685 women included were similar in characteristics to each other as well as to the other potentially eligible women not included in the analysis.
 

Sleep disturbance patterns compared

At baseline, sleep disturbance patterns were similar between the two groups. Among medication users, the mean score for difficulty initiating sleep was 2.7 (95% confidence interval, 2.5-2.9), waking frequently 3.8 (95% CI, 3.6-3.9), and waking early 2.9 (95% CI, 2.7-3.1). Among the nonusers, the baseline scores were 2.6 (95% CI, 2.5-2.7), 3.7 (95% CI, 3.6-3.8), and 2.7 (95% CI, 2.5-2.8), respectively. After 1 year, there was no statistically significant difference in scores between the two groups. The average ratings for medication users were 2.6 (95% CI, 2.3-2.8) for difficulty initiating sleep, 3.8 (95% CI, 3.6-4.0) for waking frequently, and 2.8 (95% CI, 2.6-3.0) for waking early.

Average ratings among nonusers were 2.3 (95% CI, 2.2-2.4), 3.5 (95% CI, 3.3-3.6), and 2.5 (95% CI, 2.3-2.6), respectively.

After 2 years, there were still no statistically significant reductions in sleep disturbances among those taking prescription sleep medications, compared with those not taking medication.

The researchers noted that approximately half of the women in this cohort were current or past tobacco users and that 20% were moderate to heavy alcohol users.
 

More work-up, not more medication, needed

The study authors acknowledged the limitations of an observational study and noted that, since participants only reported medication use and sleep disturbances at annual visits, they did not know whether patients’ medication use was intermittent or of any interim outcomes. Additionally, the authors pointed out that those classified as “nonusers” may have been using over-the-counter medication.

“Investigations should look at detailed-use patterns, on a daily or weekly basis, with frequent outcomes data,” Dr. Solomon said in an interview. “While our data shed new light on chronic use, we only had data collected on an annual basis; daily or weekly data would provide more granular information.”

Regarding clinician prescribing practices, Dr. Solomon said, “short-term, intermittent use can be helpful, but use these agents sparingly” and “educate patients that chronic regular use of medications for sleep is not associated with improvement in sleep disturbances.”

Commenting on the study, Andrea Matsumura, MD, a sleep specialist at the Oregon Clinic in Portland, echoed this sentiment: “When someone says they are having trouble sleeping this is the tip of the iceberg and it warrants an evaluation to determine if someone has a breathing disorder, a circadian disorder, a life situation, or a type of insomnia that is driving the sleeplessness.”

“I think this study supports what we all should know,” Dr. Matsumura concluded. “Sleep aids are not meant to be used long term” and should not be used for longer than 2 weeks without further work-up.

Funding for this study was provided through a grant from the National Institutes of Health. Dr. Solomon has received salary support from research grants to Brigham and Women’s Hospital for unrelated work from AbbVie, Amgen, Corrona, Genentech and Pfizer. The other authors and Dr. Matsumura have reported no relevant financial relationships.

Perimenopausal women are using prescription sleep medications for long periods of time despite no evidence of efficacy, a new study shows.

“While there are good data from [randomized, controlled trials] that these medications improve sleep disturbances in the short term,” few studies have examined whether they provide long-term benefits, stated the authors of the paper, which was published in BMJ Open.

“The current observational study does not support use of sleep medications over the long term, as there were no self-reported differences at 1 or 2 years of follow-up comparing sleep medication users with nonusers,” author Daniel H. Solomon, MD, MPH, from Brigham and Women’s Hospital, Boston, and colleagues wrote.

Women included in the analysis were drawn from the Study of Women’s Health Across the Nation (SWAN), an ongoing multicenter, longitudinal study examining women during the menopausal transition. The average age of the women included in the cohort was 49.5 years and approximately half were White. All women reported a sleep disturbance on at least 3 nights per week during a 2-week interval. At follow up, women were asked to use a Likert scale to rate three aspects of sleep: difficulty initiating sleep, frequent awakening, and waking up early. On the scale, 1 represented having no difficulties on any nights, 3 represented having difficulties 1-2 nights per week, and 5 represented having difficulty 5-7 nights per week.

Women already using prescription sleep medication at their baseline visit were excluded from the study. Medications used included benzodiazepines, selective BZD receptor agonists, and other hypnotics.

Over the 21 years of follow-up in the SWAN study (1995-2016), Dr. Solomon and colleagues identified 238 women using sleep medication and these were compared with a cohort of 447 propensity score–matched non–sleep medication uses. Overall, the 685 women included were similar in characteristics to each other as well as to the other potentially eligible women not included in the analysis.
 

Sleep disturbance patterns compared

At baseline, sleep disturbance patterns were similar between the two groups. Among medication users, the mean score for difficulty initiating sleep was 2.7 (95% confidence interval, 2.5-2.9), waking frequently 3.8 (95% CI, 3.6-3.9), and waking early 2.9 (95% CI, 2.7-3.1). Among the nonusers, the baseline scores were 2.6 (95% CI, 2.5-2.7), 3.7 (95% CI, 3.6-3.8), and 2.7 (95% CI, 2.5-2.8), respectively. After 1 year, there was no statistically significant difference in scores between the two groups. The average ratings for medication users were 2.6 (95% CI, 2.3-2.8) for difficulty initiating sleep, 3.8 (95% CI, 3.6-4.0) for waking frequently, and 2.8 (95% CI, 2.6-3.0) for waking early.

Average ratings among nonusers were 2.3 (95% CI, 2.2-2.4), 3.5 (95% CI, 3.3-3.6), and 2.5 (95% CI, 2.3-2.6), respectively.

After 2 years, there were still no statistically significant reductions in sleep disturbances among those taking prescription sleep medications, compared with those not taking medication.

The researchers noted that approximately half of the women in this cohort were current or past tobacco users and that 20% were moderate to heavy alcohol users.
 

More work-up, not more medication, needed

The study authors acknowledged the limitations of an observational study and noted that, since participants only reported medication use and sleep disturbances at annual visits, they did not know whether patients’ medication use was intermittent or of any interim outcomes. Additionally, the authors pointed out that those classified as “nonusers” may have been using over-the-counter medication.

“Investigations should look at detailed-use patterns, on a daily or weekly basis, with frequent outcomes data,” Dr. Solomon said in an interview. “While our data shed new light on chronic use, we only had data collected on an annual basis; daily or weekly data would provide more granular information.”

Regarding clinician prescribing practices, Dr. Solomon said, “short-term, intermittent use can be helpful, but use these agents sparingly” and “educate patients that chronic regular use of medications for sleep is not associated with improvement in sleep disturbances.”

Commenting on the study, Andrea Matsumura, MD, a sleep specialist at the Oregon Clinic in Portland, echoed this sentiment: “When someone says they are having trouble sleeping this is the tip of the iceberg and it warrants an evaluation to determine if someone has a breathing disorder, a circadian disorder, a life situation, or a type of insomnia that is driving the sleeplessness.”

“I think this study supports what we all should know,” Dr. Matsumura concluded. “Sleep aids are not meant to be used long term” and should not be used for longer than 2 weeks without further work-up.

Funding for this study was provided through a grant from the National Institutes of Health. Dr. Solomon has received salary support from research grants to Brigham and Women’s Hospital for unrelated work from AbbVie, Amgen, Corrona, Genentech and Pfizer. The other authors and Dr. Matsumura have reported no relevant financial relationships.

The use of e-cigarettes is linked to a higher frequency of self-reported wheezing and shortness of breath in adolescents and young adults, according to an online survey. The association was present even after controlling for cigarette and cannabis use.

Previous studies of adolescents and young adults have shown associations between e-cigarette use and wheeze, shortness of breath, and asthma. The Youth Risk Behavior Surveillance (YRBS) survey by the Centers for Disease Control and Prevention and other health agencies, conducted from 2015 to 2017, found that 63.5% of youth who used e-cigarettes also used some combination of cigarettes and cannabis. Combined use was associated with a 55%-65% increased odds of self-reported asthma.

The Population Assessment of Tobacco and Health (PATH) study, which was published in October 2020, had similar findings, though it did not find an association between e-cigarette use alone and wheezing.

“The findings from the current study highlight that we need to keep asking young people about respiratory symptoms, couse of other tobacco products, as well as cannabis use. As more products, including cannabis and various e-cigarette devices, enter the market, assessing respiratory health will be important both where adolescents and young adults receive their health care and in research,” Alayna Tackett, PhD, said in an interview. Dr. Tackett presented the study at the American Thoracic Society’s virtual international conference. She is an assistant professor of preventive medicine at the University of Southern California, Los Angeles.

“I found [the study] very interesting because it seems to be identifying a physiologic response to these e-cigarettes,” said Christopher Pascoe, MD, who was asked to comment. “And they were so young [age 14-21 years]. The fact that these symptoms of wheezing and shortness of breath are coming from people who are this young suggests that there may be chronic problems showing up later with continued use of these devices.”

Dr. Pascoe is an assistant professor of physiology and pathophysiology at the University of Manitoba, Winnipeg, where he also works with the Children’s Hospital Research Institute of Manitoba. His own research examines lung tissue harvested from pneumothorax surgeries in smokers and e-cigarette users to identify markers of inflammation.

He called the research a “good start” at unraveling the impacts of e-cigarettes and smoking, since some people use both products. “The fact that there was still a twofold increase in odds for wheezing, shortness of breath among people who use these e-cigarettes, but weren’t using cannabis and weren’t using cigarettes. I think it’s novel, and it suggests that there is an effect [of e-cigarettes alone].”

The study is based on a self-reported data, which is a significant limitation, especially considering that asthma is often overreported. “Self-report can be fraught with things, but I think it’s an interesting starting point for trying to recruit people who are just e-cigarette users and following them up further,” said Dr. Pascoe.

The researchers surveyed 2,931 individuals aged 14-21 years between Aug. 6 and Aug.30, 2020, with an average age of 18.9 years. Of the respondents, 80% were women and girls, and 75% were White. The high percentage of women and girls was unusual. Dr. Tackett provided no explanation for the atypical demographic but noted that the current study used convenience sampling.

The survey asked about use of e-cigarettes, cigarettes, and cannabis in the past 30 days, as well as asthma diagnosis and respiratory symptoms over the same period. The methodology employed survey management company Lucid, which recruited, collected data from, and provided compensation to participants.

A total of 24% of participants reported asthma, 13% reported wheeze, and 20% reported shortness of breath. Among 1,414 respondents who reported e-cigarette use in the past 30 days, 15% also said they had used cigarettes, and 37% said they had used cannabis.

After controlling for age, birth sex, and race/ethnicity, compared with self-reported never e-cigarette users, there was an association between past 30-day e-cigarette use and self-reported asthma (odds ratio, 1.4; 95% CI, 1.1-1.7), wheeze (OR, 3.1; 95% CI, 2.3-4.2), and shortness of breath (OR, 2.9; 95% CI, 2.3-3.6). After the researchers controlled for past 30-day cigarette cannabis use, the association with asthma was no longer statistically significant (OR, 1.11; 95% CI, 0.87-1.41), but the association with wheeze (OR, 2.3; 95% CI, 1.6-3.0) and shortness of breath (OR, 2.1; 95% CI, 1.6-2.8) remained.

Dr. Tackett noted that wheeze and shortness of breath are only two indicators of respiratory health, and more research needs to be done. Her team is conducting follow-up studies using objective measurement tools such as home-based spirometry in adolescents and young adults who exclusively use e-cigarettes and who have never used e-cigarettes.

“We need to better understand the complex relationships between use of these products and whether multiple product use is associated with worse respiratory outcomes,” said Dr. Tackett.

Dr. Pascoe and Dr. Tackett disclosed no relevant financial relationships.

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

The use of e-cigarettes is linked to a higher frequency of self-reported wheezing and shortness of breath in adolescents and young adults, according to an online survey. The association was present even after controlling for cigarette and cannabis use.

Previous studies of adolescents and young adults have shown associations between e-cigarette use and wheeze, shortness of breath, and asthma. The Youth Risk Behavior Surveillance (YRBS) survey by the Centers for Disease Control and Prevention and other health agencies, conducted from 2015 to 2017, found that 63.5% of youth who used e-cigarettes also used some combination of cigarettes and cannabis. Combined use was associated with a 55%-65% increased odds of self-reported asthma.

The Population Assessment of Tobacco and Health (PATH) study, which was published in October 2020, had similar findings, though it did not find an association between e-cigarette use alone and wheezing.

“The findings from the current study highlight that we need to keep asking young people about respiratory symptoms, couse of other tobacco products, as well as cannabis use. As more products, including cannabis and various e-cigarette devices, enter the market, assessing respiratory health will be important both where adolescents and young adults receive their health care and in research,” Alayna Tackett, PhD, said in an interview. Dr. Tackett presented the study at the American Thoracic Society’s virtual international conference. She is an assistant professor of preventive medicine at the University of Southern California, Los Angeles.

“I found [the study] very interesting because it seems to be identifying a physiologic response to these e-cigarettes,” said Christopher Pascoe, MD, who was asked to comment. “And they were so young [age 14-21 years]. The fact that these symptoms of wheezing and shortness of breath are coming from people who are this young suggests that there may be chronic problems showing up later with continued use of these devices.”

Dr. Pascoe is an assistant professor of physiology and pathophysiology at the University of Manitoba, Winnipeg, where he also works with the Children’s Hospital Research Institute of Manitoba. His own research examines lung tissue harvested from pneumothorax surgeries in smokers and e-cigarette users to identify markers of inflammation.

He called the research a “good start” at unraveling the impacts of e-cigarettes and smoking, since some people use both products. “The fact that there was still a twofold increase in odds for wheezing, shortness of breath among people who use these e-cigarettes, but weren’t using cannabis and weren’t using cigarettes. I think it’s novel, and it suggests that there is an effect [of e-cigarettes alone].”

The study is based on a self-reported data, which is a significant limitation, especially considering that asthma is often overreported. “Self-report can be fraught with things, but I think it’s an interesting starting point for trying to recruit people who are just e-cigarette users and following them up further,” said Dr. Pascoe.

The researchers surveyed 2,931 individuals aged 14-21 years between Aug. 6 and Aug.30, 2020, with an average age of 18.9 years. Of the respondents, 80% were women and girls, and 75% were White. The high percentage of women and girls was unusual. Dr. Tackett provided no explanation for the atypical demographic but noted that the current study used convenience sampling.

The survey asked about use of e-cigarettes, cigarettes, and cannabis in the past 30 days, as well as asthma diagnosis and respiratory symptoms over the same period. The methodology employed survey management company Lucid, which recruited, collected data from, and provided compensation to participants.

A total of 24% of participants reported asthma, 13% reported wheeze, and 20% reported shortness of breath. Among 1,414 respondents who reported e-cigarette use in the past 30 days, 15% also said they had used cigarettes, and 37% said they had used cannabis.

After controlling for age, birth sex, and race/ethnicity, compared with self-reported never e-cigarette users, there was an association between past 30-day e-cigarette use and self-reported asthma (odds ratio, 1.4; 95% CI, 1.1-1.7), wheeze (OR, 3.1; 95% CI, 2.3-4.2), and shortness of breath (OR, 2.9; 95% CI, 2.3-3.6). After the researchers controlled for past 30-day cigarette cannabis use, the association with asthma was no longer statistically significant (OR, 1.11; 95% CI, 0.87-1.41), but the association with wheeze (OR, 2.3; 95% CI, 1.6-3.0) and shortness of breath (OR, 2.1; 95% CI, 1.6-2.8) remained.

Dr. Tackett noted that wheeze and shortness of breath are only two indicators of respiratory health, and more research needs to be done. Her team is conducting follow-up studies using objective measurement tools such as home-based spirometry in adolescents and young adults who exclusively use e-cigarettes and who have never used e-cigarettes.

“We need to better understand the complex relationships between use of these products and whether multiple product use is associated with worse respiratory outcomes,” said Dr. Tackett.

Dr. Pascoe and Dr. Tackett disclosed no relevant financial relationships.

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

The use of e-cigarettes is linked to a higher frequency of self-reported wheezing and shortness of breath in adolescents and young adults, according to an online survey. The association was present even after controlling for cigarette and cannabis use.

Previous studies of adolescents and young adults have shown associations between e-cigarette use and wheeze, shortness of breath, and asthma. The Youth Risk Behavior Surveillance (YRBS) survey by the Centers for Disease Control and Prevention and other health agencies, conducted from 2015 to 2017, found that 63.5% of youth who used e-cigarettes also used some combination of cigarettes and cannabis. Combined use was associated with a 55%-65% increased odds of self-reported asthma.

The Population Assessment of Tobacco and Health (PATH) study, which was published in October 2020, had similar findings, though it did not find an association between e-cigarette use alone and wheezing.

“The findings from the current study highlight that we need to keep asking young people about respiratory symptoms, couse of other tobacco products, as well as cannabis use. As more products, including cannabis and various e-cigarette devices, enter the market, assessing respiratory health will be important both where adolescents and young adults receive their health care and in research,” Alayna Tackett, PhD, said in an interview. Dr. Tackett presented the study at the American Thoracic Society’s virtual international conference. She is an assistant professor of preventive medicine at the University of Southern California, Los Angeles.

“I found [the study] very interesting because it seems to be identifying a physiologic response to these e-cigarettes,” said Christopher Pascoe, MD, who was asked to comment. “And they were so young [age 14-21 years]. The fact that these symptoms of wheezing and shortness of breath are coming from people who are this young suggests that there may be chronic problems showing up later with continued use of these devices.”

Dr. Pascoe is an assistant professor of physiology and pathophysiology at the University of Manitoba, Winnipeg, where he also works with the Children’s Hospital Research Institute of Manitoba. His own research examines lung tissue harvested from pneumothorax surgeries in smokers and e-cigarette users to identify markers of inflammation.

He called the research a “good start” at unraveling the impacts of e-cigarettes and smoking, since some people use both products. “The fact that there was still a twofold increase in odds for wheezing, shortness of breath among people who use these e-cigarettes, but weren’t using cannabis and weren’t using cigarettes. I think it’s novel, and it suggests that there is an effect [of e-cigarettes alone].”

The study is based on a self-reported data, which is a significant limitation, especially considering that asthma is often overreported. “Self-report can be fraught with things, but I think it’s an interesting starting point for trying to recruit people who are just e-cigarette users and following them up further,” said Dr. Pascoe.

The researchers surveyed 2,931 individuals aged 14-21 years between Aug. 6 and Aug.30, 2020, with an average age of 18.9 years. Of the respondents, 80% were women and girls, and 75% were White. The high percentage of women and girls was unusual. Dr. Tackett provided no explanation for the atypical demographic but noted that the current study used convenience sampling.

The survey asked about use of e-cigarettes, cigarettes, and cannabis in the past 30 days, as well as asthma diagnosis and respiratory symptoms over the same period. The methodology employed survey management company Lucid, which recruited, collected data from, and provided compensation to participants.

A total of 24% of participants reported asthma, 13% reported wheeze, and 20% reported shortness of breath. Among 1,414 respondents who reported e-cigarette use in the past 30 days, 15% also said they had used cigarettes, and 37% said they had used cannabis.

After controlling for age, birth sex, and race/ethnicity, compared with self-reported never e-cigarette users, there was an association between past 30-day e-cigarette use and self-reported asthma (odds ratio, 1.4; 95% CI, 1.1-1.7), wheeze (OR, 3.1; 95% CI, 2.3-4.2), and shortness of breath (OR, 2.9; 95% CI, 2.3-3.6). After the researchers controlled for past 30-day cigarette cannabis use, the association with asthma was no longer statistically significant (OR, 1.11; 95% CI, 0.87-1.41), but the association with wheeze (OR, 2.3; 95% CI, 1.6-3.0) and shortness of breath (OR, 2.1; 95% CI, 1.6-2.8) remained.

Dr. Tackett noted that wheeze and shortness of breath are only two indicators of respiratory health, and more research needs to be done. Her team is conducting follow-up studies using objective measurement tools such as home-based spirometry in adolescents and young adults who exclusively use e-cigarettes and who have never used e-cigarettes.

“We need to better understand the complex relationships between use of these products and whether multiple product use is associated with worse respiratory outcomes,” said Dr. Tackett.

Dr. Pascoe and Dr. Tackett disclosed no relevant financial relationships.

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

The use of bioactive ingredients culled from the marine environment has increased significantly in recent years for use in skin care because of the reputed antioxidant and anti-aging activity of these substances.^1-3

ingwio/Getty Images

In the last couple of decades, secondary metabolites with bioactive properties have been identified in seaweeds. Among these substances, phlorotannins have been isolated from brown seaweeds and demonstrated to exhibit anti-allergic, anti-inflammatory, antioxidant, anticancer, and antiwrinkling activity, as well as some capacity to promote hair growth.⁴ Sanjeewa et al. suggest that phlorotannins, or marine polyphenols, derived from brown seaweed are well suited for use in cosmeceutical formulations and appear to exhibit skin whitening and antiwrinkling properties in particular.⁴ This column will discuss recent findings regarding the use of marine ingredients in cosmetic formulations, with a particular focus on substances such as fucoidan, as well as emerging evidence regarding the benefits to human skin derived from salmon eggs.

Recent studies of marine products in cosmetic formulations

In 2017, Fabrowska et al. showed in two groups of 10 volunteers each (one ranging from 20 to 30 years old and one from 40 to 50 years old) that the freshwater alga Cladophora glomerate is an effective ingredient for use as a cosmetic agent intended to moisturize and firm the skin.⁵

The next year, Thu et al. reported on the preparation of a cream mask composed of Vietnamese seaweeds (Caulerpa lentillifera, Sargassum crassifolium, Ulva reticulata, and Kappaphycus alvarezii), which they found to be abundant in proteins, polysaccharides, carotenoids, and other vitamins and to have potent antibacterial, cell proliferation, moisture retention, and tyrosinase inhibitory properties. The authors added that the seaweed cream mask was safe, provoked no irritation, and appeared to be effective in delivering anti-aging and moisturizing benefits.⁶

In 2019, Jesumani et al., in reviewing the potential cutaneous benefits of bioactive substances in seaweed, noted a significant increase in the use of ingredients found in macroalgae or seaweed in cosmetic formulations, also noting the range of reputed bioactivity (i.e., antioxidant, antitumor, anti-inflammatory, antilipidemic, antimicrobial, and anti-allergic).⁷ Seaweeds are a significant source of vitamins A, B, C, D, and E, and green, red, and brown algae contain pigments that protect against UV irradiation.^7,8

Also that year, Hameury et al. conducted an ex vivo assessment to predict the cutaneous anti-aging benefits of an aqueous gel containing 6.1% marine ingredients (amino acid-enriched giant kelp extract, trace element-enriched seawater, and dedifferentiated sea fennel cells) topically applied on human skin explants. The investigators found that 64 proteins were significantly regulated by the gel when marine ingredients were compared with untreated skin explants, with the ingredients shown to act on the epidermis and dermis. These proteins are involved in multiple functions including gene expression, inflammatory processes, dermal extracellular matrix production, and melanogenesis and keratinocyte proliferation, suggesting, according to the authors, that marine ingredients could play a role in preventing cutaneous aging and contributing to the health of the epidermis and dermis.⁹

Early in 2020, Poulose et al. reported on the first use of a photoprotective cosmetic cream combining nanomelanin and seaweed that exerts antioxidant, antibacterial, and wound healing activity.¹⁰

The skin-lightening potential of fucoidan

In 2017, Wang et al. investigated the antimelanogenic activity of fucoidan – a complex sulfated polysaccharide extracted from brown seaweed known to possess a broad array of biologic functions – on B16 murine melanoma cells. Their in vitro studies revealed that fucoidan suppresses B16 melanoma cell proliferation and cellular tyrosinase activity and has potential as a skin-whitening cosmeceutical agent.¹¹

Two years later, Jesumani et al. investigated the polysaccharides extracted from the seaweed species Sargassum vachellianum, S. horneri, and S. hemiphyllum. Found to be abundant in fucose, all of the evaluated polysaccharides demonstrated dose-dependent antioxidant activity and effectiveness in hindering tyrosinase and elastase. The researchers concluded that all of the tested species display potential as key ingredients in cosmeceutical agents intended to treat wrinkles or lighten skin.¹²

More recently, a comparative study by the same team revealed that both fucoidan-rich polysaccharide extract and polyphenol-rich extract from the seaweed S. vachellianum delivered significant protective activity. Both protected the skin from UV harm: The fucoidan-rich extract showed superior free radical scavenging and antimicrobial activity, while the polyphenol extract performed better at absorbing UV radiation. The investigators suggested that both extracts could provide a balanced approach to skin protection when featured in skin care products.¹³

In addition, it is worth noting that a key monomeric component of red macroalgae (Rhodophyta), 3,6-anhydro-l-galactose, has been found in vitro to display skin-whitening activity.¹⁴

Salmon eggs

In a 2013 double-blind, randomized clinical trial with 66 patients, Lønne et al. reported that subjects treated topically with salmon egg extract experienced significant amelioration of photoaging, including wrinkles, pigmentation, erythema, and xerosis, yielding global skin appearance improvement.^3,15

A pilot study by Mekas et al., which was reported 2 years later and included 75 patients, revealed that skin tone and evenness were improved by a topical exfoliative cream featuring hydrolyzed roe proteins, based on subjective and objective measures comparing 4% glycolic acid.^3,16

In 2016, Yoshino et al. showed that human dermal fibroblasts incubated with salmon egg extract upregulated the expression of collagen type I genes and several oxidative genes.^3,17 The topical application of hydrolyzed salmon roe proteins to human skin has also been demonstrated to eliminate cell-to-cell adhesions thus ameliorating the appearance of photodamaged skin.^1,3,16

More recently, a comprehensive PubMed search on the bioactive ingredients used in Korean cosmeceuticals reported early in 2020 that there is increased interest in salmon eggs because they provide a copious supply of unsaturated fatty acids, proteins, vitamins, and minerals known to nurture cutaneous health.^3,15

Conclusion

Seaweed and other marine life forms have been considered a rich source for cosmetic and cosmeceutical products for several years. Research into the numerous bioactive properties of these multitudinous species has ramped up in recent years and is yielding evidence regarding the efficacy and potential broader uses of such ingredients in cutaneous health care. As we build on our understanding of just how dynamic a source of treatment options may lie under the sea, we become increasingly aware, ironically, of the damage that human industrialization exerts on the planet, as well as these precious marine resources (including the possibly deleterious effects of chemical sunscreens like those that are now banned for sale in Hawai‘i). Humanity will need to become much better stewards of the Earth if we are to enhance our future opportunities and possibly harness the potent marine ingredients still available with the potential to enhance skin health and appearance.

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

References

1. Kim SK. J Cosmet Dermatol. 2014;13(1):56-67.

2. Venkatesan J et al. Mar Drugs. 2017;15(5):1-18.

3. Nguyen JK et al. J Cosmet Dermatol 2020 Jul;19(7):1555-69.

4. Sanjeewa KKA et al. J Photochem Photobiol B. 2016 Sep;162:100-5.

5. Fabrowska J et al. Acta Pol Pharm. 2017 Mar;74(2):633-41.

6. Thu NTH et al. J Cosmet Sci. Nov/Dec 2018;69(6):447-62.

7. Jesumani V et al. Mar Drugs. 2019 Dec 6;17(12):688.

8. Kim MS et al. Photochem Photobiol. Jul-Aug 2013;89(4):911-8.

9. Hameury S et al. J Cosmet Dermatol. 2019 Feb;18(1):355-70.

10. Poulose N et al. J Photochem Photobiol B. 2020 Apr;205:111816.

11. Wang ZJ et al. Afr J Tradit Complement Altern Med. 2017 Jun 5;14(4);149-55.

12. Jesumani V et al. Int J Biol Macromol. 2019 Nov 1;140:216-24.

13. Jesumani V et al. PLoS One. 2020 Jan 7;15(1):e0227308.

14. Kim JH et al. Mar Drugs. 2017 Oct 20;15(10):321.

15. Lønne GK et al. Int J Cosmet Sci. 2013 Oct;35(5):515-22.

16. Mekas M et al. J Drugs Dermatol. 2015 Nov;14(11):1306-19.

17. Yoshino A et al. Clin Interv Aging. 2016;11:1159-68.

The use of bioactive ingredients culled from the marine environment has increased significantly in recent years for use in skin care because of the reputed antioxidant and anti-aging activity of these substances.^1-3

ingwio/Getty Images

In the last couple of decades, secondary metabolites with bioactive properties have been identified in seaweeds. Among these substances, phlorotannins have been isolated from brown seaweeds and demonstrated to exhibit anti-allergic, anti-inflammatory, antioxidant, anticancer, and antiwrinkling activity, as well as some capacity to promote hair growth.⁴ Sanjeewa et al. suggest that phlorotannins, or marine polyphenols, derived from brown seaweed are well suited for use in cosmeceutical formulations and appear to exhibit skin whitening and antiwrinkling properties in particular.⁴ This column will discuss recent findings regarding the use of marine ingredients in cosmetic formulations, with a particular focus on substances such as fucoidan, as well as emerging evidence regarding the benefits to human skin derived from salmon eggs.

Recent studies of marine products in cosmetic formulations

In 2017, Fabrowska et al. showed in two groups of 10 volunteers each (one ranging from 20 to 30 years old and one from 40 to 50 years old) that the freshwater alga Cladophora glomerate is an effective ingredient for use as a cosmetic agent intended to moisturize and firm the skin.⁵

The next year, Thu et al. reported on the preparation of a cream mask composed of Vietnamese seaweeds (Caulerpa lentillifera, Sargassum crassifolium, Ulva reticulata, and Kappaphycus alvarezii), which they found to be abundant in proteins, polysaccharides, carotenoids, and other vitamins and to have potent antibacterial, cell proliferation, moisture retention, and tyrosinase inhibitory properties. The authors added that the seaweed cream mask was safe, provoked no irritation, and appeared to be effective in delivering anti-aging and moisturizing benefits.⁶

In 2019, Jesumani et al., in reviewing the potential cutaneous benefits of bioactive substances in seaweed, noted a significant increase in the use of ingredients found in macroalgae or seaweed in cosmetic formulations, also noting the range of reputed bioactivity (i.e., antioxidant, antitumor, anti-inflammatory, antilipidemic, antimicrobial, and anti-allergic).⁷ Seaweeds are a significant source of vitamins A, B, C, D, and E, and green, red, and brown algae contain pigments that protect against UV irradiation.^7,8

Also that year, Hameury et al. conducted an ex vivo assessment to predict the cutaneous anti-aging benefits of an aqueous gel containing 6.1% marine ingredients (amino acid-enriched giant kelp extract, trace element-enriched seawater, and dedifferentiated sea fennel cells) topically applied on human skin explants. The investigators found that 64 proteins were significantly regulated by the gel when marine ingredients were compared with untreated skin explants, with the ingredients shown to act on the epidermis and dermis. These proteins are involved in multiple functions including gene expression, inflammatory processes, dermal extracellular matrix production, and melanogenesis and keratinocyte proliferation, suggesting, according to the authors, that marine ingredients could play a role in preventing cutaneous aging and contributing to the health of the epidermis and dermis.⁹

Early in 2020, Poulose et al. reported on the first use of a photoprotective cosmetic cream combining nanomelanin and seaweed that exerts antioxidant, antibacterial, and wound healing activity.¹⁰

The skin-lightening potential of fucoidan

In 2017, Wang et al. investigated the antimelanogenic activity of fucoidan – a complex sulfated polysaccharide extracted from brown seaweed known to possess a broad array of biologic functions – on B16 murine melanoma cells. Their in vitro studies revealed that fucoidan suppresses B16 melanoma cell proliferation and cellular tyrosinase activity and has potential as a skin-whitening cosmeceutical agent.¹¹

Two years later, Jesumani et al. investigated the polysaccharides extracted from the seaweed species Sargassum vachellianum, S. horneri, and S. hemiphyllum. Found to be abundant in fucose, all of the evaluated polysaccharides demonstrated dose-dependent antioxidant activity and effectiveness in hindering tyrosinase and elastase. The researchers concluded that all of the tested species display potential as key ingredients in cosmeceutical agents intended to treat wrinkles or lighten skin.¹²

More recently, a comparative study by the same team revealed that both fucoidan-rich polysaccharide extract and polyphenol-rich extract from the seaweed S. vachellianum delivered significant protective activity. Both protected the skin from UV harm: The fucoidan-rich extract showed superior free radical scavenging and antimicrobial activity, while the polyphenol extract performed better at absorbing UV radiation. The investigators suggested that both extracts could provide a balanced approach to skin protection when featured in skin care products.¹³

In addition, it is worth noting that a key monomeric component of red macroalgae (Rhodophyta), 3,6-anhydro-l-galactose, has been found in vitro to display skin-whitening activity.¹⁴

Salmon eggs

In a 2013 double-blind, randomized clinical trial with 66 patients, Lønne et al. reported that subjects treated topically with salmon egg extract experienced significant amelioration of photoaging, including wrinkles, pigmentation, erythema, and xerosis, yielding global skin appearance improvement.^3,15

A pilot study by Mekas et al., which was reported 2 years later and included 75 patients, revealed that skin tone and evenness were improved by a topical exfoliative cream featuring hydrolyzed roe proteins, based on subjective and objective measures comparing 4% glycolic acid.^3,16

In 2016, Yoshino et al. showed that human dermal fibroblasts incubated with salmon egg extract upregulated the expression of collagen type I genes and several oxidative genes.^3,17 The topical application of hydrolyzed salmon roe proteins to human skin has also been demonstrated to eliminate cell-to-cell adhesions thus ameliorating the appearance of photodamaged skin.^1,3,16

More recently, a comprehensive PubMed search on the bioactive ingredients used in Korean cosmeceuticals reported early in 2020 that there is increased interest in salmon eggs because they provide a copious supply of unsaturated fatty acids, proteins, vitamins, and minerals known to nurture cutaneous health.^3,15

Conclusion

Seaweed and other marine life forms have been considered a rich source for cosmetic and cosmeceutical products for several years. Research into the numerous bioactive properties of these multitudinous species has ramped up in recent years and is yielding evidence regarding the efficacy and potential broader uses of such ingredients in cutaneous health care. As we build on our understanding of just how dynamic a source of treatment options may lie under the sea, we become increasingly aware, ironically, of the damage that human industrialization exerts on the planet, as well as these precious marine resources (including the possibly deleterious effects of chemical sunscreens like those that are now banned for sale in Hawai‘i). Humanity will need to become much better stewards of the Earth if we are to enhance our future opportunities and possibly harness the potent marine ingredients still available with the potential to enhance skin health and appearance.

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

References

1. Kim SK. J Cosmet Dermatol. 2014;13(1):56-67.

2. Venkatesan J et al. Mar Drugs. 2017;15(5):1-18.

3. Nguyen JK et al. J Cosmet Dermatol 2020 Jul;19(7):1555-69.

4. Sanjeewa KKA et al. J Photochem Photobiol B. 2016 Sep;162:100-5.

5. Fabrowska J et al. Acta Pol Pharm. 2017 Mar;74(2):633-41.

6. Thu NTH et al. J Cosmet Sci. Nov/Dec 2018;69(6):447-62.

7. Jesumani V et al. Mar Drugs. 2019 Dec 6;17(12):688.

8. Kim MS et al. Photochem Photobiol. Jul-Aug 2013;89(4):911-8.

9. Hameury S et al. J Cosmet Dermatol. 2019 Feb;18(1):355-70.

10. Poulose N et al. J Photochem Photobiol B. 2020 Apr;205:111816.

11. Wang ZJ et al. Afr J Tradit Complement Altern Med. 2017 Jun 5;14(4);149-55.

12. Jesumani V et al. Int J Biol Macromol. 2019 Nov 1;140:216-24.

13. Jesumani V et al. PLoS One. 2020 Jan 7;15(1):e0227308.

14. Kim JH et al. Mar Drugs. 2017 Oct 20;15(10):321.

15. Lønne GK et al. Int J Cosmet Sci. 2013 Oct;35(5):515-22.

16. Mekas M et al. J Drugs Dermatol. 2015 Nov;14(11):1306-19.

17. Yoshino A et al. Clin Interv Aging. 2016;11:1159-68.

The use of bioactive ingredients culled from the marine environment has increased significantly in recent years for use in skin care because of the reputed antioxidant and anti-aging activity of these substances.^1-3

ingwio/Getty Images

In the last couple of decades, secondary metabolites with bioactive properties have been identified in seaweeds. Among these substances, phlorotannins have been isolated from brown seaweeds and demonstrated to exhibit anti-allergic, anti-inflammatory, antioxidant, anticancer, and antiwrinkling activity, as well as some capacity to promote hair growth.⁴ Sanjeewa et al. suggest that phlorotannins, or marine polyphenols, derived from brown seaweed are well suited for use in cosmeceutical formulations and appear to exhibit skin whitening and antiwrinkling properties in particular.⁴ This column will discuss recent findings regarding the use of marine ingredients in cosmetic formulations, with a particular focus on substances such as fucoidan, as well as emerging evidence regarding the benefits to human skin derived from salmon eggs.

Recent studies of marine products in cosmetic formulations

In 2017, Fabrowska et al. showed in two groups of 10 volunteers each (one ranging from 20 to 30 years old and one from 40 to 50 years old) that the freshwater alga Cladophora glomerate is an effective ingredient for use as a cosmetic agent intended to moisturize and firm the skin.⁵

The next year, Thu et al. reported on the preparation of a cream mask composed of Vietnamese seaweeds (Caulerpa lentillifera, Sargassum crassifolium, Ulva reticulata, and Kappaphycus alvarezii), which they found to be abundant in proteins, polysaccharides, carotenoids, and other vitamins and to have potent antibacterial, cell proliferation, moisture retention, and tyrosinase inhibitory properties. The authors added that the seaweed cream mask was safe, provoked no irritation, and appeared to be effective in delivering anti-aging and moisturizing benefits.⁶

In 2019, Jesumani et al., in reviewing the potential cutaneous benefits of bioactive substances in seaweed, noted a significant increase in the use of ingredients found in macroalgae or seaweed in cosmetic formulations, also noting the range of reputed bioactivity (i.e., antioxidant, antitumor, anti-inflammatory, antilipidemic, antimicrobial, and anti-allergic).⁷ Seaweeds are a significant source of vitamins A, B, C, D, and E, and green, red, and brown algae contain pigments that protect against UV irradiation.^7,8

Also that year, Hameury et al. conducted an ex vivo assessment to predict the cutaneous anti-aging benefits of an aqueous gel containing 6.1% marine ingredients (amino acid-enriched giant kelp extract, trace element-enriched seawater, and dedifferentiated sea fennel cells) topically applied on human skin explants. The investigators found that 64 proteins were significantly regulated by the gel when marine ingredients were compared with untreated skin explants, with the ingredients shown to act on the epidermis and dermis. These proteins are involved in multiple functions including gene expression, inflammatory processes, dermal extracellular matrix production, and melanogenesis and keratinocyte proliferation, suggesting, according to the authors, that marine ingredients could play a role in preventing cutaneous aging and contributing to the health of the epidermis and dermis.⁹

Early in 2020, Poulose et al. reported on the first use of a photoprotective cosmetic cream combining nanomelanin and seaweed that exerts antioxidant, antibacterial, and wound healing activity.¹⁰

The skin-lightening potential of fucoidan

In 2017, Wang et al. investigated the antimelanogenic activity of fucoidan – a complex sulfated polysaccharide extracted from brown seaweed known to possess a broad array of biologic functions – on B16 murine melanoma cells. Their in vitro studies revealed that fucoidan suppresses B16 melanoma cell proliferation and cellular tyrosinase activity and has potential as a skin-whitening cosmeceutical agent.¹¹

Two years later, Jesumani et al. investigated the polysaccharides extracted from the seaweed species Sargassum vachellianum, S. horneri, and S. hemiphyllum. Found to be abundant in fucose, all of the evaluated polysaccharides demonstrated dose-dependent antioxidant activity and effectiveness in hindering tyrosinase and elastase. The researchers concluded that all of the tested species display potential as key ingredients in cosmeceutical agents intended to treat wrinkles or lighten skin.¹²

More recently, a comparative study by the same team revealed that both fucoidan-rich polysaccharide extract and polyphenol-rich extract from the seaweed S. vachellianum delivered significant protective activity. Both protected the skin from UV harm: The fucoidan-rich extract showed superior free radical scavenging and antimicrobial activity, while the polyphenol extract performed better at absorbing UV radiation. The investigators suggested that both extracts could provide a balanced approach to skin protection when featured in skin care products.¹³

In addition, it is worth noting that a key monomeric component of red macroalgae (Rhodophyta), 3,6-anhydro-l-galactose, has been found in vitro to display skin-whitening activity.¹⁴

Salmon eggs

In a 2013 double-blind, randomized clinical trial with 66 patients, Lønne et al. reported that subjects treated topically with salmon egg extract experienced significant amelioration of photoaging, including wrinkles, pigmentation, erythema, and xerosis, yielding global skin appearance improvement.^3,15

A pilot study by Mekas et al., which was reported 2 years later and included 75 patients, revealed that skin tone and evenness were improved by a topical exfoliative cream featuring hydrolyzed roe proteins, based on subjective and objective measures comparing 4% glycolic acid.^3,16

In 2016, Yoshino et al. showed that human dermal fibroblasts incubated with salmon egg extract upregulated the expression of collagen type I genes and several oxidative genes.^3,17 The topical application of hydrolyzed salmon roe proteins to human skin has also been demonstrated to eliminate cell-to-cell adhesions thus ameliorating the appearance of photodamaged skin.^1,3,16

More recently, a comprehensive PubMed search on the bioactive ingredients used in Korean cosmeceuticals reported early in 2020 that there is increased interest in salmon eggs because they provide a copious supply of unsaturated fatty acids, proteins, vitamins, and minerals known to nurture cutaneous health.^3,15

Conclusion

Seaweed and other marine life forms have been considered a rich source for cosmetic and cosmeceutical products for several years. Research into the numerous bioactive properties of these multitudinous species has ramped up in recent years and is yielding evidence regarding the efficacy and potential broader uses of such ingredients in cutaneous health care. As we build on our understanding of just how dynamic a source of treatment options may lie under the sea, we become increasingly aware, ironically, of the damage that human industrialization exerts on the planet, as well as these precious marine resources (including the possibly deleterious effects of chemical sunscreens like those that are now banned for sale in Hawai‘i). Humanity will need to become much better stewards of the Earth if we are to enhance our future opportunities and possibly harness the potent marine ingredients still available with the potential to enhance skin health and appearance.

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

References

1. Kim SK. J Cosmet Dermatol. 2014;13(1):56-67.

2. Venkatesan J et al. Mar Drugs. 2017;15(5):1-18.

3. Nguyen JK et al. J Cosmet Dermatol 2020 Jul;19(7):1555-69.

4. Sanjeewa KKA et al. J Photochem Photobiol B. 2016 Sep;162:100-5.

5. Fabrowska J et al. Acta Pol Pharm. 2017 Mar;74(2):633-41.

6. Thu NTH et al. J Cosmet Sci. Nov/Dec 2018;69(6):447-62.

7. Jesumani V et al. Mar Drugs. 2019 Dec 6;17(12):688.

8. Kim MS et al. Photochem Photobiol. Jul-Aug 2013;89(4):911-8.

9. Hameury S et al. J Cosmet Dermatol. 2019 Feb;18(1):355-70.

10. Poulose N et al. J Photochem Photobiol B. 2020 Apr;205:111816.

11. Wang ZJ et al. Afr J Tradit Complement Altern Med. 2017 Jun 5;14(4);149-55.

12. Jesumani V et al. Int J Biol Macromol. 2019 Nov 1;140:216-24.

13. Jesumani V et al. PLoS One. 2020 Jan 7;15(1):e0227308.

14. Kim JH et al. Mar Drugs. 2017 Oct 20;15(10):321.

15. Lønne GK et al. Int J Cosmet Sci. 2013 Oct;35(5):515-22.

16. Mekas M et al. J Drugs Dermatol. 2015 Nov;14(11):1306-19.

17. Yoshino A et al. Clin Interv Aging. 2016;11:1159-68.

Finerenone treatment of patients with type 2 diabetes and diabetic kidney disease was linked to a significant drop in the incidence of new-onset atrial fibrillation as a prespecified, exploratory endpoint of the FIDELIO-DKD pivotal trial that randomized more than 5,700 patients.

Treatment with finerenone linked with a 29% relative reduction compared with placebo in incident cases of atrial fibrillation (AFib), Gerasimos Filippatos, MD, reported at the annual scientific sessions of the American College of Cardiology.

The absolute reduction was modest, a 1.3% reduction from the 4.5% incidence rate on placebo to a 3.2% rate on finerenone during a median 2.6 years of follow-up. Concurrently with the report, the results appeared online (J Am Coll Cardiol. 2021 May 17. doi: 10.1016/j.jacc.2021.04.079).

The analyses Dr. Filippatos presented also showed that whether or not patients had a history of AFib, there was no impact on either the primary benefit from finerenone treatment seen in FIDELIO-DKD, which was a significant 18% relative risk reduction compared with placebo in the combined rate of kidney failure, a 40% or greater decline from baseline in estimated glomerular filtration rate, or renal death.

Likewise, prior AFib status had no effect on the study’s key secondary endpoint, a significant 14% relative risk reduction in the combined rate of cardiovascular death, nonfatal MI, nonfatal stroke, or hospitalization for heart failure.

The primary results from FIDELIO-DKD (Efficacy and Safety of Finerenone in Subjects With Type 2 Diabetes Mellitus and Diabetic Kidney Disease) appeared in a 2020 report (N Engl J Med. 2020 Dec 3;383[23];2219-29).
 

‘Side benefits can be very helpful’

“It’s important to know of finerenone’s benefits beyond the primary outcome of a trial because side benefits can be very helpful,” said Anne B. Curtis, MD, an electrophysiologist and professor and chair of medicine at the University of Buffalo (N.Y.) School of Medicine and Biomedical Sciences. “It’s not a huge benefit, but this could be an added benefit for selected patients,” she said during a press briefing. “Background studies had shown favorable remodeling of the heart [by finerenone] that could affect AFib.”

Possible mitigating effects by finerenone on inflammation and fibrosis might also mediate the drug’s apparent effect on AFib, said Dr. Filippatos, professor of cardiology and director of the Heart Failure and Cardio-Oncology Clinic at Attikon University Hospital and the University of Athens.

He noted that additional data addressing a possible AFib effect of finerenone will emerge soon from the FIGARO-DKD trial, which enrolled patients similar to those in FIDELIO-DKD but with more moderate stages of kidney disease, and from the FINEARTS-HF trial, which is examining the effect of finerenone in patients with heart failure with an ejection fraction of at least 40%.

“Heart failure and AFib go together tightly. It’s worth studying this specifically, so we can see whether there is an impact of finerenone on patients with heart failure who may not necessarily have kidney disease or diabetes,” Dr. Curtis said.
 

Hypothesis-generating findings

The new findings reported by Dr. Filippatos “should be considered hypothesis generating. Until we have more information, upstream therapies, including mineralocorticoid receptor antagonists [MRAs, the umbrella drug class that includes finerenone], should be used in appropriate patient populations based on defined benefits with the hope they will also reduce the development of AFib and atrial flutter over time,” Gerald V. Naccarelli, MD, and coauthors wrote in an editorial that accompanied the report (J Am Coll Cardiol. 2021 May 17. doi: 10.1016/j.jacc.2021.04.080).

The FIDELIO-DKD trial randomized 5,734 patients at 913 sites in 48 countries, including 461 patients with a history of AFib. The observed link of finerenone treatment with a reduced incidence of AFib appeared consistent regardless of patients’ age, sex, race, their kidney characteristics at baseline, baseline levels of systolic blood pressure, serum potassium, body mass index, A1c, or use of glucose-lowering medications.

Finerenone belongs to a new class of MRAs that have a nonsteroidal structure, in contrast with the MRAs spironolactone and eplerenone. This means that finerenone does not produce steroidal-associated adverse effects linked with certain other MRAs, such as gynecomastia, and may also differ in other actions.

FIDELIO-DKD was sponsored by Bayer, the company developing finerenone. Dr. Filippatos has received lecture fees from or participated in the direction of trials on behalf of Bayer, as well as for Amgen, Boehringer Ingelheim, Medtronic, Novartis, Servier, and Vifor. Dr. Curtis is an adviser to and receives honoraria from St. Jude Medical, and receives honoraria from Medtronic. Dr. Naccarelli has been a consultant to Acesion, ARCA, GlaxoSmithKline, Janssen, Milestone, Omeicos, and Sanofi. His coauthors had no disclosures.

[email protected]

Finerenone treatment of patients with type 2 diabetes and diabetic kidney disease was linked to a significant drop in the incidence of new-onset atrial fibrillation as a prespecified, exploratory endpoint of the FIDELIO-DKD pivotal trial that randomized more than 5,700 patients.

Treatment with finerenone linked with a 29% relative reduction compared with placebo in incident cases of atrial fibrillation (AFib), Gerasimos Filippatos, MD, reported at the annual scientific sessions of the American College of Cardiology.

The absolute reduction was modest, a 1.3% reduction from the 4.5% incidence rate on placebo to a 3.2% rate on finerenone during a median 2.6 years of follow-up. Concurrently with the report, the results appeared online (J Am Coll Cardiol. 2021 May 17. doi: 10.1016/j.jacc.2021.04.079).

The analyses Dr. Filippatos presented also showed that whether or not patients had a history of AFib, there was no impact on either the primary benefit from finerenone treatment seen in FIDELIO-DKD, which was a significant 18% relative risk reduction compared with placebo in the combined rate of kidney failure, a 40% or greater decline from baseline in estimated glomerular filtration rate, or renal death.

Likewise, prior AFib status had no effect on the study’s key secondary endpoint, a significant 14% relative risk reduction in the combined rate of cardiovascular death, nonfatal MI, nonfatal stroke, or hospitalization for heart failure.

The primary results from FIDELIO-DKD (Efficacy and Safety of Finerenone in Subjects With Type 2 Diabetes Mellitus and Diabetic Kidney Disease) appeared in a 2020 report (N Engl J Med. 2020 Dec 3;383[23];2219-29).
 

‘Side benefits can be very helpful’

“It’s important to know of finerenone’s benefits beyond the primary outcome of a trial because side benefits can be very helpful,” said Anne B. Curtis, MD, an electrophysiologist and professor and chair of medicine at the University of Buffalo (N.Y.) School of Medicine and Biomedical Sciences. “It’s not a huge benefit, but this could be an added benefit for selected patients,” she said during a press briefing. “Background studies had shown favorable remodeling of the heart [by finerenone] that could affect AFib.”

Possible mitigating effects by finerenone on inflammation and fibrosis might also mediate the drug’s apparent effect on AFib, said Dr. Filippatos, professor of cardiology and director of the Heart Failure and Cardio-Oncology Clinic at Attikon University Hospital and the University of Athens.

He noted that additional data addressing a possible AFib effect of finerenone will emerge soon from the FIGARO-DKD trial, which enrolled patients similar to those in FIDELIO-DKD but with more moderate stages of kidney disease, and from the FINEARTS-HF trial, which is examining the effect of finerenone in patients with heart failure with an ejection fraction of at least 40%.

“Heart failure and AFib go together tightly. It’s worth studying this specifically, so we can see whether there is an impact of finerenone on patients with heart failure who may not necessarily have kidney disease or diabetes,” Dr. Curtis said.
 

Hypothesis-generating findings

The new findings reported by Dr. Filippatos “should be considered hypothesis generating. Until we have more information, upstream therapies, including mineralocorticoid receptor antagonists [MRAs, the umbrella drug class that includes finerenone], should be used in appropriate patient populations based on defined benefits with the hope they will also reduce the development of AFib and atrial flutter over time,” Gerald V. Naccarelli, MD, and coauthors wrote in an editorial that accompanied the report (J Am Coll Cardiol. 2021 May 17. doi: 10.1016/j.jacc.2021.04.080).

The FIDELIO-DKD trial randomized 5,734 patients at 913 sites in 48 countries, including 461 patients with a history of AFib. The observed link of finerenone treatment with a reduced incidence of AFib appeared consistent regardless of patients’ age, sex, race, their kidney characteristics at baseline, baseline levels of systolic blood pressure, serum potassium, body mass index, A1c, or use of glucose-lowering medications.

Finerenone belongs to a new class of MRAs that have a nonsteroidal structure, in contrast with the MRAs spironolactone and eplerenone. This means that finerenone does not produce steroidal-associated adverse effects linked with certain other MRAs, such as gynecomastia, and may also differ in other actions.

FIDELIO-DKD was sponsored by Bayer, the company developing finerenone. Dr. Filippatos has received lecture fees from or participated in the direction of trials on behalf of Bayer, as well as for Amgen, Boehringer Ingelheim, Medtronic, Novartis, Servier, and Vifor. Dr. Curtis is an adviser to and receives honoraria from St. Jude Medical, and receives honoraria from Medtronic. Dr. Naccarelli has been a consultant to Acesion, ARCA, GlaxoSmithKline, Janssen, Milestone, Omeicos, and Sanofi. His coauthors had no disclosures.

[email protected]

Finerenone treatment of patients with type 2 diabetes and diabetic kidney disease was linked to a significant drop in the incidence of new-onset atrial fibrillation as a prespecified, exploratory endpoint of the FIDELIO-DKD pivotal trial that randomized more than 5,700 patients.

Treatment with finerenone linked with a 29% relative reduction compared with placebo in incident cases of atrial fibrillation (AFib), Gerasimos Filippatos, MD, reported at the annual scientific sessions of the American College of Cardiology.

The absolute reduction was modest, a 1.3% reduction from the 4.5% incidence rate on placebo to a 3.2% rate on finerenone during a median 2.6 years of follow-up. Concurrently with the report, the results appeared online (J Am Coll Cardiol. 2021 May 17. doi: 10.1016/j.jacc.2021.04.079).

The analyses Dr. Filippatos presented also showed that whether or not patients had a history of AFib, there was no impact on either the primary benefit from finerenone treatment seen in FIDELIO-DKD, which was a significant 18% relative risk reduction compared with placebo in the combined rate of kidney failure, a 40% or greater decline from baseline in estimated glomerular filtration rate, or renal death.

Likewise, prior AFib status had no effect on the study’s key secondary endpoint, a significant 14% relative risk reduction in the combined rate of cardiovascular death, nonfatal MI, nonfatal stroke, or hospitalization for heart failure.

The primary results from FIDELIO-DKD (Efficacy and Safety of Finerenone in Subjects With Type 2 Diabetes Mellitus and Diabetic Kidney Disease) appeared in a 2020 report (N Engl J Med. 2020 Dec 3;383[23];2219-29).
 

‘Side benefits can be very helpful’

“It’s important to know of finerenone’s benefits beyond the primary outcome of a trial because side benefits can be very helpful,” said Anne B. Curtis, MD, an electrophysiologist and professor and chair of medicine at the University of Buffalo (N.Y.) School of Medicine and Biomedical Sciences. “It’s not a huge benefit, but this could be an added benefit for selected patients,” she said during a press briefing. “Background studies had shown favorable remodeling of the heart [by finerenone] that could affect AFib.”

Possible mitigating effects by finerenone on inflammation and fibrosis might also mediate the drug’s apparent effect on AFib, said Dr. Filippatos, professor of cardiology and director of the Heart Failure and Cardio-Oncology Clinic at Attikon University Hospital and the University of Athens.

He noted that additional data addressing a possible AFib effect of finerenone will emerge soon from the FIGARO-DKD trial, which enrolled patients similar to those in FIDELIO-DKD but with more moderate stages of kidney disease, and from the FINEARTS-HF trial, which is examining the effect of finerenone in patients with heart failure with an ejection fraction of at least 40%.

“Heart failure and AFib go together tightly. It’s worth studying this specifically, so we can see whether there is an impact of finerenone on patients with heart failure who may not necessarily have kidney disease or diabetes,” Dr. Curtis said.
 

Hypothesis-generating findings

The new findings reported by Dr. Filippatos “should be considered hypothesis generating. Until we have more information, upstream therapies, including mineralocorticoid receptor antagonists [MRAs, the umbrella drug class that includes finerenone], should be used in appropriate patient populations based on defined benefits with the hope they will also reduce the development of AFib and atrial flutter over time,” Gerald V. Naccarelli, MD, and coauthors wrote in an editorial that accompanied the report (J Am Coll Cardiol. 2021 May 17. doi: 10.1016/j.jacc.2021.04.080).

The FIDELIO-DKD trial randomized 5,734 patients at 913 sites in 48 countries, including 461 patients with a history of AFib. The observed link of finerenone treatment with a reduced incidence of AFib appeared consistent regardless of patients’ age, sex, race, their kidney characteristics at baseline, baseline levels of systolic blood pressure, serum potassium, body mass index, A1c, or use of glucose-lowering medications.

Finerenone belongs to a new class of MRAs that have a nonsteroidal structure, in contrast with the MRAs spironolactone and eplerenone. This means that finerenone does not produce steroidal-associated adverse effects linked with certain other MRAs, such as gynecomastia, and may also differ in other actions.

FIDELIO-DKD was sponsored by Bayer, the company developing finerenone. Dr. Filippatos has received lecture fees from or participated in the direction of trials on behalf of Bayer, as well as for Amgen, Boehringer Ingelheim, Medtronic, Novartis, Servier, and Vifor. Dr. Curtis is an adviser to and receives honoraria from St. Jude Medical, and receives honoraria from Medtronic. Dr. Naccarelli has been a consultant to Acesion, ARCA, GlaxoSmithKline, Janssen, Milestone, Omeicos, and Sanofi. His coauthors had no disclosures.

[email protected]

In patients hospitalized with COVID-19 infection, the sodium-glucose transporter 2 inhibitor dapagliflozin showed a trend for benefit relative to placebo on multiple outcomes, including the primary outcome of time to organ failure or death, according to results from the randomized DARE-19 trial.

Because of the failure to reach statistical significance, these results have no immediate relevance, but the trends support interest in further testing SGLT2 inhibitors in acute diseases posing a high risk for organ failure, according to Mikhail Kosiborod, MD.

In a trial that did not meet its primary endpoint, Dr. Kosiborod acknowledged that positive interpretations are speculative, but he does believe that there is one immediate take-home message.

“Our results do not support discontinuation of SGLT2 inhibitors in the setting of COVID-19 as long as patients are monitored,” said Dr. Kosiborod, director of cardiometabolic research at Saint Luke’s Mid-America Heart Institute, Kansas City, Mo.

At many institutions, it has been common to discontinue SGLT2 inhibitors in patients admitted with COVID-19. One reason was the concern that drugs in this class could exacerbate organ damage, particularly if they were to induced ketoacidosis. However, only 2 (0.003%) of 613 patients treated with dapagliflozin developed ketoacidosis, and the signal for organ protection overall, although not significant, was consistent.

“Numerically, fewer patients treated with dapagliflozin experienced organ failure and death, and this was consistent across systems, including the kidney,” Dr. Kosiborod said in presenting the study at the annual scientific sessions of the American College of Cardiology.

Overall, the study suggests that, in the context of COVID-19, dapagliflozin did not show harm and might have potential benefit, he added.

DARE-19 was rapidly conceived, designed, and implemented during the early stages of the COVID-19 pandemic. Based on prior evidence that SGLT2 inhibitors “favorably affect a number of pathophysiologic pathways disrupted during acute illness” and that drugs in this class have provided organ protection in the context of heart failure, chronic kidney disease, and other cardiometabolic conditions, the study was designed to test the hypothesis that this mechanism might improve outcomes in patients hospitalized with COVID-19, Dr. Kosiborod said.

The entry criteria included confirmed or suspected COVID-19 with an onset of 4 days of fewer and one additional risk factor, such as atherosclerotic cardiovascular disease, hypertension, or type 2 diabetes. Patients with significant renal impairment or a history of diabetic ketoacidosis were excluded.

On top of standard treatments for COVID-19, patients were randomized to 10 mg dapagliflozin or placebo once daily. There were two primary endpoints. That of prevention was time to criteria for respiratory, cardiovascular, or renal organ failure or death. The second primary outcome, for recovery, was a hierarchical composite for four endpoints: death, organ failure, status at 30 days if hospitalized, and time to discharge if this occurred before day 30.

Of the 1,250 patients randomized at 95 sites in seven countries, 617 in the dapagliflozin group and 620 patients in the placebo group completed the study. Baseline characteristics, which included a mean of age of 62 years; types of comorbidities; and types of treatments were similar.
 

Results for two primary endpoints

The curves for the primary outcome of prevention had already separated by day 3 and continued to widen over the 30 days in which outcomes were compared. At the end of 30 days, 11.2% of the dapagliflozin group and 13.8% of the placebo group had an event. By hazard ratio, dapagliflozin was linked to 20% nonsignificant relative protection from events (hazard ratio, 0.80; 95% confidence interval, 0.58-1.10).

The trend (P = .168) for the primary endpoint for prevention was reflected in the individual components. For dapagliflozin related to placebo, there were generally similar or greater reductions in new or worsening organ failure (HR, 0.80), cardiac decompensation (HR, 0.81), respiratory decompensation (HR, 0.85), and kidney decompensation (HR, 0.65). None were statistically significant, but the confidence intervals were tight with the upper end never exceeding 1.20.

Moreover, the relative risk reduction for all-cause mortality moved in the same direction (HR, 0.77; 95% CI, 0.52-1.16).

In the hierarchical composite endpoint of recovery, there was no significant difference in the time to discharge, but again many recovery metrics numerically favored dapagliflozin with an overall difference producing a statistical trend (P = .14) similar to organ failure events and death.

In safety analyses, dapagliflozin consistently outperformed placebo across a broad array of safety measure, including any severe adverse event (65% vs. 82%), any adverse event with an outcome of death (32% vs. 48%), discontinuation caused by an adverse event (44% vs. 55%), and acute kidney injury (21% vs. 34%).
 

Data could fuel related studies

According to Ana Barac, MD, PhD, director of the cardio-oncology program in the Medstar Heart and Vascular Institute, Washington, these data are “thought provoking.” Although this was a negative trial, she said that it generates an “exciting hypothesis” about the potential of SGLT2 inhibitors to provide organ protection. She called for studies to pursue this path of research.

More immediately, Dr. Barac agreed that these data argue against stopping SGLT2 inhibitors in patients admitted to a hospital for COVID-19 infection.

“These data show that these drugs are not going to lead to harm, but they might lead to benefit,” she said.

For James Januzzi, MD, a cardiologist at Massachusetts General Hospital and professor of medicine at Harvard Medical School, both in Boston, DARE-19 was perhaps most impressive because of its rigorous design and execution in the midst of a pandemic.

Over the past year, “the medical literature was flooded with grossly underpowered, poorly designed, single-center studies” yielding results that have been hard to interpret, Dr. Januzzi said. Despite the fact that this study failed to confirm its hypothesis, he said the investigators deserve praise for the quality of the work.

Courtesy Massachusetts General Hospital

Dr. Januzzi also believes the study is not without clinically relevant findings, particularly the fact that dapagliflozin was associated with a lower rate of adverse events than placebo. This, at least, provides reassurance about the safety of this drug in the setting of COVID-19 infection.

Dr. Kosiborod reported financial relationships with more than 10 pharmaceutical companies, including AstraZeneca, which provided funding for DARE-19. Dr. Barac reported financial relationships with Bristol-Myers Squibb and CTI BioPharma. Dr. Januzzi reported financial relationships with Boehringer Ingelheim, GE Healthcare, Johnson & Johnson, Merck, Novartis, Pfizer, and Roche.

In patients hospitalized with COVID-19 infection, the sodium-glucose transporter 2 inhibitor dapagliflozin showed a trend for benefit relative to placebo on multiple outcomes, including the primary outcome of time to organ failure or death, according to results from the randomized DARE-19 trial.

Because of the failure to reach statistical significance, these results have no immediate relevance, but the trends support interest in further testing SGLT2 inhibitors in acute diseases posing a high risk for organ failure, according to Mikhail Kosiborod, MD.

In a trial that did not meet its primary endpoint, Dr. Kosiborod acknowledged that positive interpretations are speculative, but he does believe that there is one immediate take-home message.

“Our results do not support discontinuation of SGLT2 inhibitors in the setting of COVID-19 as long as patients are monitored,” said Dr. Kosiborod, director of cardiometabolic research at Saint Luke’s Mid-America Heart Institute, Kansas City, Mo.

At many institutions, it has been common to discontinue SGLT2 inhibitors in patients admitted with COVID-19. One reason was the concern that drugs in this class could exacerbate organ damage, particularly if they were to induced ketoacidosis. However, only 2 (0.003%) of 613 patients treated with dapagliflozin developed ketoacidosis, and the signal for organ protection overall, although not significant, was consistent.

“Numerically, fewer patients treated with dapagliflozin experienced organ failure and death, and this was consistent across systems, including the kidney,” Dr. Kosiborod said in presenting the study at the annual scientific sessions of the American College of Cardiology.

Overall, the study suggests that, in the context of COVID-19, dapagliflozin did not show harm and might have potential benefit, he added.

DARE-19 was rapidly conceived, designed, and implemented during the early stages of the COVID-19 pandemic. Based on prior evidence that SGLT2 inhibitors “favorably affect a number of pathophysiologic pathways disrupted during acute illness” and that drugs in this class have provided organ protection in the context of heart failure, chronic kidney disease, and other cardiometabolic conditions, the study was designed to test the hypothesis that this mechanism might improve outcomes in patients hospitalized with COVID-19, Dr. Kosiborod said.

The entry criteria included confirmed or suspected COVID-19 with an onset of 4 days of fewer and one additional risk factor, such as atherosclerotic cardiovascular disease, hypertension, or type 2 diabetes. Patients with significant renal impairment or a history of diabetic ketoacidosis were excluded.

On top of standard treatments for COVID-19, patients were randomized to 10 mg dapagliflozin or placebo once daily. There were two primary endpoints. That of prevention was time to criteria for respiratory, cardiovascular, or renal organ failure or death. The second primary outcome, for recovery, was a hierarchical composite for four endpoints: death, organ failure, status at 30 days if hospitalized, and time to discharge if this occurred before day 30.

Of the 1,250 patients randomized at 95 sites in seven countries, 617 in the dapagliflozin group and 620 patients in the placebo group completed the study. Baseline characteristics, which included a mean of age of 62 years; types of comorbidities; and types of treatments were similar.
 

Results for two primary endpoints

The curves for the primary outcome of prevention had already separated by day 3 and continued to widen over the 30 days in which outcomes were compared. At the end of 30 days, 11.2% of the dapagliflozin group and 13.8% of the placebo group had an event. By hazard ratio, dapagliflozin was linked to 20% nonsignificant relative protection from events (hazard ratio, 0.80; 95% confidence interval, 0.58-1.10).

The trend (P = .168) for the primary endpoint for prevention was reflected in the individual components. For dapagliflozin related to placebo, there were generally similar or greater reductions in new or worsening organ failure (HR, 0.80), cardiac decompensation (HR, 0.81), respiratory decompensation (HR, 0.85), and kidney decompensation (HR, 0.65). None were statistically significant, but the confidence intervals were tight with the upper end never exceeding 1.20.

Moreover, the relative risk reduction for all-cause mortality moved in the same direction (HR, 0.77; 95% CI, 0.52-1.16).

In the hierarchical composite endpoint of recovery, there was no significant difference in the time to discharge, but again many recovery metrics numerically favored dapagliflozin with an overall difference producing a statistical trend (P = .14) similar to organ failure events and death.

In safety analyses, dapagliflozin consistently outperformed placebo across a broad array of safety measure, including any severe adverse event (65% vs. 82%), any adverse event with an outcome of death (32% vs. 48%), discontinuation caused by an adverse event (44% vs. 55%), and acute kidney injury (21% vs. 34%).
 

Data could fuel related studies

According to Ana Barac, MD, PhD, director of the cardio-oncology program in the Medstar Heart and Vascular Institute, Washington, these data are “thought provoking.” Although this was a negative trial, she said that it generates an “exciting hypothesis” about the potential of SGLT2 inhibitors to provide organ protection. She called for studies to pursue this path of research.

More immediately, Dr. Barac agreed that these data argue against stopping SGLT2 inhibitors in patients admitted to a hospital for COVID-19 infection.

“These data show that these drugs are not going to lead to harm, but they might lead to benefit,” she said.

For James Januzzi, MD, a cardiologist at Massachusetts General Hospital and professor of medicine at Harvard Medical School, both in Boston, DARE-19 was perhaps most impressive because of its rigorous design and execution in the midst of a pandemic.

Over the past year, “the medical literature was flooded with grossly underpowered, poorly designed, single-center studies” yielding results that have been hard to interpret, Dr. Januzzi said. Despite the fact that this study failed to confirm its hypothesis, he said the investigators deserve praise for the quality of the work.

Courtesy Massachusetts General Hospital

Dr. Januzzi also believes the study is not without clinically relevant findings, particularly the fact that dapagliflozin was associated with a lower rate of adverse events than placebo. This, at least, provides reassurance about the safety of this drug in the setting of COVID-19 infection.

Dr. Kosiborod reported financial relationships with more than 10 pharmaceutical companies, including AstraZeneca, which provided funding for DARE-19. Dr. Barac reported financial relationships with Bristol-Myers Squibb and CTI BioPharma. Dr. Januzzi reported financial relationships with Boehringer Ingelheim, GE Healthcare, Johnson & Johnson, Merck, Novartis, Pfizer, and Roche.

In patients hospitalized with COVID-19 infection, the sodium-glucose transporter 2 inhibitor dapagliflozin showed a trend for benefit relative to placebo on multiple outcomes, including the primary outcome of time to organ failure or death, according to results from the randomized DARE-19 trial.

Because of the failure to reach statistical significance, these results have no immediate relevance, but the trends support interest in further testing SGLT2 inhibitors in acute diseases posing a high risk for organ failure, according to Mikhail Kosiborod, MD.

In a trial that did not meet its primary endpoint, Dr. Kosiborod acknowledged that positive interpretations are speculative, but he does believe that there is one immediate take-home message.

“Our results do not support discontinuation of SGLT2 inhibitors in the setting of COVID-19 as long as patients are monitored,” said Dr. Kosiborod, director of cardiometabolic research at Saint Luke’s Mid-America Heart Institute, Kansas City, Mo.

At many institutions, it has been common to discontinue SGLT2 inhibitors in patients admitted with COVID-19. One reason was the concern that drugs in this class could exacerbate organ damage, particularly if they were to induced ketoacidosis. However, only 2 (0.003%) of 613 patients treated with dapagliflozin developed ketoacidosis, and the signal for organ protection overall, although not significant, was consistent.

“Numerically, fewer patients treated with dapagliflozin experienced organ failure and death, and this was consistent across systems, including the kidney,” Dr. Kosiborod said in presenting the study at the annual scientific sessions of the American College of Cardiology.

Overall, the study suggests that, in the context of COVID-19, dapagliflozin did not show harm and might have potential benefit, he added.

DARE-19 was rapidly conceived, designed, and implemented during the early stages of the COVID-19 pandemic. Based on prior evidence that SGLT2 inhibitors “favorably affect a number of pathophysiologic pathways disrupted during acute illness” and that drugs in this class have provided organ protection in the context of heart failure, chronic kidney disease, and other cardiometabolic conditions, the study was designed to test the hypothesis that this mechanism might improve outcomes in patients hospitalized with COVID-19, Dr. Kosiborod said.

The entry criteria included confirmed or suspected COVID-19 with an onset of 4 days of fewer and one additional risk factor, such as atherosclerotic cardiovascular disease, hypertension, or type 2 diabetes. Patients with significant renal impairment or a history of diabetic ketoacidosis were excluded.

On top of standard treatments for COVID-19, patients were randomized to 10 mg dapagliflozin or placebo once daily. There were two primary endpoints. That of prevention was time to criteria for respiratory, cardiovascular, or renal organ failure or death. The second primary outcome, for recovery, was a hierarchical composite for four endpoints: death, organ failure, status at 30 days if hospitalized, and time to discharge if this occurred before day 30.

Of the 1,250 patients randomized at 95 sites in seven countries, 617 in the dapagliflozin group and 620 patients in the placebo group completed the study. Baseline characteristics, which included a mean of age of 62 years; types of comorbidities; and types of treatments were similar.
 

Results for two primary endpoints

The curves for the primary outcome of prevention had already separated by day 3 and continued to widen over the 30 days in which outcomes were compared. At the end of 30 days, 11.2% of the dapagliflozin group and 13.8% of the placebo group had an event. By hazard ratio, dapagliflozin was linked to 20% nonsignificant relative protection from events (hazard ratio, 0.80; 95% confidence interval, 0.58-1.10).

The trend (P = .168) for the primary endpoint for prevention was reflected in the individual components. For dapagliflozin related to placebo, there were generally similar or greater reductions in new or worsening organ failure (HR, 0.80), cardiac decompensation (HR, 0.81), respiratory decompensation (HR, 0.85), and kidney decompensation (HR, 0.65). None were statistically significant, but the confidence intervals were tight with the upper end never exceeding 1.20.

Moreover, the relative risk reduction for all-cause mortality moved in the same direction (HR, 0.77; 95% CI, 0.52-1.16).

In the hierarchical composite endpoint of recovery, there was no significant difference in the time to discharge, but again many recovery metrics numerically favored dapagliflozin with an overall difference producing a statistical trend (P = .14) similar to organ failure events and death.

In safety analyses, dapagliflozin consistently outperformed placebo across a broad array of safety measure, including any severe adverse event (65% vs. 82%), any adverse event with an outcome of death (32% vs. 48%), discontinuation caused by an adverse event (44% vs. 55%), and acute kidney injury (21% vs. 34%).
 

Data could fuel related studies

According to Ana Barac, MD, PhD, director of the cardio-oncology program in the Medstar Heart and Vascular Institute, Washington, these data are “thought provoking.” Although this was a negative trial, she said that it generates an “exciting hypothesis” about the potential of SGLT2 inhibitors to provide organ protection. She called for studies to pursue this path of research.

More immediately, Dr. Barac agreed that these data argue against stopping SGLT2 inhibitors in patients admitted to a hospital for COVID-19 infection.

“These data show that these drugs are not going to lead to harm, but they might lead to benefit,” she said.

For James Januzzi, MD, a cardiologist at Massachusetts General Hospital and professor of medicine at Harvard Medical School, both in Boston, DARE-19 was perhaps most impressive because of its rigorous design and execution in the midst of a pandemic.

Over the past year, “the medical literature was flooded with grossly underpowered, poorly designed, single-center studies” yielding results that have been hard to interpret, Dr. Januzzi said. Despite the fact that this study failed to confirm its hypothesis, he said the investigators deserve praise for the quality of the work.

Courtesy Massachusetts General Hospital

Dr. Januzzi also believes the study is not without clinically relevant findings, particularly the fact that dapagliflozin was associated with a lower rate of adverse events than placebo. This, at least, provides reassurance about the safety of this drug in the setting of COVID-19 infection.

Dr. Kosiborod reported financial relationships with more than 10 pharmaceutical companies, including AstraZeneca, which provided funding for DARE-19. Dr. Barac reported financial relationships with Bristol-Myers Squibb and CTI BioPharma. Dr. Januzzi reported financial relationships with Boehringer Ingelheim, GE Healthcare, Johnson & Johnson, Merck, Novartis, Pfizer, and Roche.

A rare, life-threatening anemia now has a new treatment option. The Food and Drug Administration announced the approval of pegcetacoplan (Empaveli) injection to treat adults with paroxysmal nocturnal hemoglobinuria (PNH). Pegcetacoplan is the first PNH treatment that binds to complement protein C3, according to the FDA announcement. Complement protein C3 is a key component of host immunity and defense.

Special concern

Because of the risk of severe side effects, the drug is available only through a restricted program under a risk evaluation and mitigation strategy (REMS). Serious infections can occur in patients taking pegcetacoplan that can become life-threatening or fatal if not treated early. According to the FDA, REMS are designed to reinforce medication use behaviors and actions that support the safe use of that medication, and only a few drugs require a REMS.

The most common other side effects are injection site reactions, diarrhea, abdominal pain, and fatigue.

Pegcetacoplan was approved based upon a study of 80 patients with PNH and anemia who had been taking eculizumab, a previously approved treatment. During 16 weeks of treatment, patients in the pegcetacoplan group had an average increase in their hemoglobin of 2.4 g/dL, while patients in the eculizumab group had an average decrease in their hemoglobin of 1.5 g/dL.
 

About the disease

PNH is caused by gene mutations that affect red blood cells, causing them to be defective and susceptible to destruction by a patient’s own immune system. Red blood cells in people with these mutations are defective and can be destroyed by the immune system, causing anemia.

Other symptoms include blood clots and destruction of bone marrow. The disease affects 1-1.5 people per million, with diagnosis typically occurring around ages 35-40, and a median survival of only 10 years after diagnosis, according to the FDA.

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A rare, life-threatening anemia now has a new treatment option. The Food and Drug Administration announced the approval of pegcetacoplan (Empaveli) injection to treat adults with paroxysmal nocturnal hemoglobinuria (PNH). Pegcetacoplan is the first PNH treatment that binds to complement protein C3, according to the FDA announcement. Complement protein C3 is a key component of host immunity and defense.

Special concern

Because of the risk of severe side effects, the drug is available only through a restricted program under a risk evaluation and mitigation strategy (REMS). Serious infections can occur in patients taking pegcetacoplan that can become life-threatening or fatal if not treated early. According to the FDA, REMS are designed to reinforce medication use behaviors and actions that support the safe use of that medication, and only a few drugs require a REMS.

The most common other side effects are injection site reactions, diarrhea, abdominal pain, and fatigue.

Pegcetacoplan was approved based upon a study of 80 patients with PNH and anemia who had been taking eculizumab, a previously approved treatment. During 16 weeks of treatment, patients in the pegcetacoplan group had an average increase in their hemoglobin of 2.4 g/dL, while patients in the eculizumab group had an average decrease in their hemoglobin of 1.5 g/dL.
 

About the disease

PNH is caused by gene mutations that affect red blood cells, causing them to be defective and susceptible to destruction by a patient’s own immune system. Red blood cells in people with these mutations are defective and can be destroyed by the immune system, causing anemia.

Other symptoms include blood clots and destruction of bone marrow. The disease affects 1-1.5 people per million, with diagnosis typically occurring around ages 35-40, and a median survival of only 10 years after diagnosis, according to the FDA.

[email protected]

A rare, life-threatening anemia now has a new treatment option. The Food and Drug Administration announced the approval of pegcetacoplan (Empaveli) injection to treat adults with paroxysmal nocturnal hemoglobinuria (PNH). Pegcetacoplan is the first PNH treatment that binds to complement protein C3, according to the FDA announcement. Complement protein C3 is a key component of host immunity and defense.

Special concern

Because of the risk of severe side effects, the drug is available only through a restricted program under a risk evaluation and mitigation strategy (REMS). Serious infections can occur in patients taking pegcetacoplan that can become life-threatening or fatal if not treated early. According to the FDA, REMS are designed to reinforce medication use behaviors and actions that support the safe use of that medication, and only a few drugs require a REMS.

The most common other side effects are injection site reactions, diarrhea, abdominal pain, and fatigue.

Pegcetacoplan was approved based upon a study of 80 patients with PNH and anemia who had been taking eculizumab, a previously approved treatment. During 16 weeks of treatment, patients in the pegcetacoplan group had an average increase in their hemoglobin of 2.4 g/dL, while patients in the eculizumab group had an average decrease in their hemoglobin of 1.5 g/dL.
 

About the disease

PNH is caused by gene mutations that affect red blood cells, causing them to be defective and susceptible to destruction by a patient’s own immune system. Red blood cells in people with these mutations are defective and can be destroyed by the immune system, causing anemia.

Other symptoms include blood clots and destruction of bone marrow. The disease affects 1-1.5 people per million, with diagnosis typically occurring around ages 35-40, and a median survival of only 10 years after diagnosis, according to the FDA.

[email protected]