Ob.Gyn. News

Factors including older age and certain comorbidities have been linked to more serious COVID-19 outcomes in previous research, and now a large dataset collected from hundreds of hospitals nationwide provides more detailed data regarding risk for mechanical ventilation and death.

Comorbidities such as cardiovascular disease, chronic kidney disease, and obesity also were associated with more severe COVID-19 outcomes in this observational study of 11,721 adults. History of pulmonary disease or smoking, interestingly, were not.

One expert urges caution when interpreting the results, however. Although the study found a number of risk factors for ventilation and mortality, she says the dataset lacks information on race and disease severity, and the sample may not be nationally representative. 

The investigators hope their level of granularity will further assist researchers searching for effective treatments and clinicians seeking to triage patients during the COVID-19 pandemic.

The study was published online August 28 in Clinical Infectious Diseases.
 

COVID-19 and comorbidities

“What I found most illuminating was this whole concept of comorbid conditions. This provides suggestive data about who we need to worry about most and who we may need to worry about less,” study author Robert S. Brown Jr, MD, MPH, told Medscape Medical News.

Comorbid conditions included hypertension in 47% of patients, diabetes in 28%, and cardiovascular disease in 19%. Another 16% were obese and 12% had chronic kidney disease. People with comorbid obesity, chronic kidney disease, and cardiovascular disease were more likely to receive mechanical ventilation compared to those without a history of these conditions in an adjusted, multivariable logistic analysis.

With the exception of obesity, the same factors were associated with risk for death during hospitalization.

In contrast, hypertension, history of smoking, and history of pulmonary disease were associated with a lower risk of needing mechanical ventilation and/or lower risk for mortality.

Furthermore, people with liver disease, gastrointestinal diseases, and even autoimmune diseases – which are likely associated with immunosuppression – “are not at that much of an increased risk that we noticed it in our data,” Brown said.

“As I tell many of my patients who have mild liver disease, for example, I would rather have mild liver disease and be on immunosuppressant therapy than be an older, obese male,” he added.

Assessing data for people in 38 U.S. states, and not limiting outcomes to patients in a particular COVID-19 hot spot, was a unique aspect of the research, said Brown, clinical chief of the Division of Gastroenterology and Hepatology at Weill Cornell Medicine in New York City.

Brown, lead author Michael W. Fried, MD, from TARGET PharmaSolutions in Durham, North Carolina, and colleagues studied adults from a commercially available Target Real-World Evidence (RWE) dataset of nearly 70,000 patients. They examined hospital chargemaster data and ICD-10 codes for COVID-19 inpatients between February 15 and April 20.

This population tended to be older, with 60% older than 60 years. A little more than half of participants, 53%, were men.
 

Key findings

A total of 21% of patients died after a median hospital length of stay of 8 days.

Older patients were significantly more likely to die, particularly those older than 60 years (P < .0001).

“This confirms some of the things we know about age and its impact on outcome,” Brown said.

The risk for mortality among patients older than 60 years was 7.2 times that of patients between 18 and 40 years in an adjusted multivariate analysis. The risk for death for those between 41 and 60 years of age was lower (odds ratio [OR], 2.6), compared with the youngest cohort.  

Men were more likely to die than women (OR, 1.5).

When asked if he was surprised by the high mortality rates, Brown said, “Having worked here in New York? No, I was not.”
 

Mechanical ventilation and mortality

Male sex, age older than 40 years, obesity, and presence of cardiovascular or chronic kidney disease were risk factors for mechanical ventilation.

Among the nearly 2,000 hospitalized adults requiring mechanical ventilation in the current report, only 27% were discharged alive. “The outcomes of people who are mechanically ventilated are really quite sobering,” Brown said.

People who ever required mechanical ventilation were 32 times more likely to die compared with others whose highest level of oxygenation was low-flow, high-flow, or no-oxygen therapy in an analysis that controlled for demographics and comorbidities.

Furthermore, patients placed on mechanical ventilation earlier – within 24 hours of admission – tended to experience better outcomes.
 

COVID-19 therapies?

Brown and colleagues also evaluated outcomes in patients who were taking either remdesivir or hydroxychloroquine. A total of 48 people were treated with remdesivir.

The four individuals receiving remdesivir who died were among 11 who were taking remdesivir and also on mechanical ventilation.

“The data for remdesivir is very encouraging,” Brown said.

Many more participants were treated with hydroxychloroquine, more than 4,200 or 36% of the total study population.

A higher proportion of people treated with hydroxychloroquine received mechanical ventilation, at 25%, versus 12% not treated with hydroxychloroquine.

The unadjusted mortality rate was also higher among those treated with the agent, at 25%, compared to 20% not receiving hydroxychloroquine.

The data with hydroxychloroquine can lead to two conclusions, Brown said: “One, it doesn’t work. Or two, it doesn’t work in the way that we use it.”

The researchers cautioned that their hydroxychloroquine findings must be interpreted carefully because those treated with the agent were also more likely to have comorbidities and greater COVID-19 disease severity.

“This study greatly contributes to understanding the natural course of COVID-19 infection by describing characteristics and outcomes of patients with COVID-19 hospitalized throughout the US,” the investigators note. “It identified categories of patients at greatest risk for poor outcomes, which should be used to prioritize prevention and treatment strategies in the future.”
 

Some limitations

“The findings that patients with hypertension and who were smokers had lower ventilation rates, and patients with hypertension, pulmonary disease, who were smokers had lower mortality risks was very surprising,” Ninez A. Ponce, PhD, MPP, told Medscape Medical News when asked to comment on the study.

Although the study identified multiple risk factors for ventilation and mortality, “unfortunately the dataset did not have race available or disease severity,” said Ponce, director of the UCLA Center for Health Policy Research and professor in the Department of Health Policy and Management at the UCLA Fielding School of Public Health.

“These omitted variables could have a considerable effect on the significance, magnitude, and direction of point estimates provided, so I would be cautious in interpreting the results as a picture of a nationally representative sample,” she said.

On a positive note, the study and dataset could illuminate the utility of medications used to treat COVID-19, Ponce said. In addition, as the authors note, “the data will expand over time.” 

Brown has reported receiving grants and consulting for Gilead. Ponce has disclosed no relevant financial relationships.
 

This article first appeared on Medscape.com.

Factors including older age and certain comorbidities have been linked to more serious COVID-19 outcomes in previous research, and now a large dataset collected from hundreds of hospitals nationwide provides more detailed data regarding risk for mechanical ventilation and death.

Comorbidities such as cardiovascular disease, chronic kidney disease, and obesity also were associated with more severe COVID-19 outcomes in this observational study of 11,721 adults. History of pulmonary disease or smoking, interestingly, were not.

One expert urges caution when interpreting the results, however. Although the study found a number of risk factors for ventilation and mortality, she says the dataset lacks information on race and disease severity, and the sample may not be nationally representative. 

The investigators hope their level of granularity will further assist researchers searching for effective treatments and clinicians seeking to triage patients during the COVID-19 pandemic.

The study was published online August 28 in Clinical Infectious Diseases.
 

COVID-19 and comorbidities

“What I found most illuminating was this whole concept of comorbid conditions. This provides suggestive data about who we need to worry about most and who we may need to worry about less,” study author Robert S. Brown Jr, MD, MPH, told Medscape Medical News.

Comorbid conditions included hypertension in 47% of patients, diabetes in 28%, and cardiovascular disease in 19%. Another 16% were obese and 12% had chronic kidney disease. People with comorbid obesity, chronic kidney disease, and cardiovascular disease were more likely to receive mechanical ventilation compared to those without a history of these conditions in an adjusted, multivariable logistic analysis.

With the exception of obesity, the same factors were associated with risk for death during hospitalization.

In contrast, hypertension, history of smoking, and history of pulmonary disease were associated with a lower risk of needing mechanical ventilation and/or lower risk for mortality.

Furthermore, people with liver disease, gastrointestinal diseases, and even autoimmune diseases – which are likely associated with immunosuppression – “are not at that much of an increased risk that we noticed it in our data,” Brown said.

“As I tell many of my patients who have mild liver disease, for example, I would rather have mild liver disease and be on immunosuppressant therapy than be an older, obese male,” he added.

Assessing data for people in 38 U.S. states, and not limiting outcomes to patients in a particular COVID-19 hot spot, was a unique aspect of the research, said Brown, clinical chief of the Division of Gastroenterology and Hepatology at Weill Cornell Medicine in New York City.

Brown, lead author Michael W. Fried, MD, from TARGET PharmaSolutions in Durham, North Carolina, and colleagues studied adults from a commercially available Target Real-World Evidence (RWE) dataset of nearly 70,000 patients. They examined hospital chargemaster data and ICD-10 codes for COVID-19 inpatients between February 15 and April 20.

This population tended to be older, with 60% older than 60 years. A little more than half of participants, 53%, were men.
 

Key findings

A total of 21% of patients died after a median hospital length of stay of 8 days.

Older patients were significantly more likely to die, particularly those older than 60 years (P < .0001).

“This confirms some of the things we know about age and its impact on outcome,” Brown said.

The risk for mortality among patients older than 60 years was 7.2 times that of patients between 18 and 40 years in an adjusted multivariate analysis. The risk for death for those between 41 and 60 years of age was lower (odds ratio [OR], 2.6), compared with the youngest cohort.  

Men were more likely to die than women (OR, 1.5).

When asked if he was surprised by the high mortality rates, Brown said, “Having worked here in New York? No, I was not.”
 

Mechanical ventilation and mortality

Male sex, age older than 40 years, obesity, and presence of cardiovascular or chronic kidney disease were risk factors for mechanical ventilation.

Among the nearly 2,000 hospitalized adults requiring mechanical ventilation in the current report, only 27% were discharged alive. “The outcomes of people who are mechanically ventilated are really quite sobering,” Brown said.

People who ever required mechanical ventilation were 32 times more likely to die compared with others whose highest level of oxygenation was low-flow, high-flow, or no-oxygen therapy in an analysis that controlled for demographics and comorbidities.

Furthermore, patients placed on mechanical ventilation earlier – within 24 hours of admission – tended to experience better outcomes.
 

COVID-19 therapies?

Brown and colleagues also evaluated outcomes in patients who were taking either remdesivir or hydroxychloroquine. A total of 48 people were treated with remdesivir.

The four individuals receiving remdesivir who died were among 11 who were taking remdesivir and also on mechanical ventilation.

“The data for remdesivir is very encouraging,” Brown said.

Many more participants were treated with hydroxychloroquine, more than 4,200 or 36% of the total study population.

A higher proportion of people treated with hydroxychloroquine received mechanical ventilation, at 25%, versus 12% not treated with hydroxychloroquine.

The unadjusted mortality rate was also higher among those treated with the agent, at 25%, compared to 20% not receiving hydroxychloroquine.

The data with hydroxychloroquine can lead to two conclusions, Brown said: “One, it doesn’t work. Or two, it doesn’t work in the way that we use it.”

The researchers cautioned that their hydroxychloroquine findings must be interpreted carefully because those treated with the agent were also more likely to have comorbidities and greater COVID-19 disease severity.

“This study greatly contributes to understanding the natural course of COVID-19 infection by describing characteristics and outcomes of patients with COVID-19 hospitalized throughout the US,” the investigators note. “It identified categories of patients at greatest risk for poor outcomes, which should be used to prioritize prevention and treatment strategies in the future.”
 

Some limitations

“The findings that patients with hypertension and who were smokers had lower ventilation rates, and patients with hypertension, pulmonary disease, who were smokers had lower mortality risks was very surprising,” Ninez A. Ponce, PhD, MPP, told Medscape Medical News when asked to comment on the study.

Although the study identified multiple risk factors for ventilation and mortality, “unfortunately the dataset did not have race available or disease severity,” said Ponce, director of the UCLA Center for Health Policy Research and professor in the Department of Health Policy and Management at the UCLA Fielding School of Public Health.

“These omitted variables could have a considerable effect on the significance, magnitude, and direction of point estimates provided, so I would be cautious in interpreting the results as a picture of a nationally representative sample,” she said.

On a positive note, the study and dataset could illuminate the utility of medications used to treat COVID-19, Ponce said. In addition, as the authors note, “the data will expand over time.” 

Brown has reported receiving grants and consulting for Gilead. Ponce has disclosed no relevant financial relationships.
 

This article first appeared on Medscape.com.

Factors including older age and certain comorbidities have been linked to more serious COVID-19 outcomes in previous research, and now a large dataset collected from hundreds of hospitals nationwide provides more detailed data regarding risk for mechanical ventilation and death.

Comorbidities such as cardiovascular disease, chronic kidney disease, and obesity also were associated with more severe COVID-19 outcomes in this observational study of 11,721 adults. History of pulmonary disease or smoking, interestingly, were not.

One expert urges caution when interpreting the results, however. Although the study found a number of risk factors for ventilation and mortality, she says the dataset lacks information on race and disease severity, and the sample may not be nationally representative. 

The investigators hope their level of granularity will further assist researchers searching for effective treatments and clinicians seeking to triage patients during the COVID-19 pandemic.

The study was published online August 28 in Clinical Infectious Diseases.
 

COVID-19 and comorbidities

“What I found most illuminating was this whole concept of comorbid conditions. This provides suggestive data about who we need to worry about most and who we may need to worry about less,” study author Robert S. Brown Jr, MD, MPH, told Medscape Medical News.

Comorbid conditions included hypertension in 47% of patients, diabetes in 28%, and cardiovascular disease in 19%. Another 16% were obese and 12% had chronic kidney disease. People with comorbid obesity, chronic kidney disease, and cardiovascular disease were more likely to receive mechanical ventilation compared to those without a history of these conditions in an adjusted, multivariable logistic analysis.

With the exception of obesity, the same factors were associated with risk for death during hospitalization.

In contrast, hypertension, history of smoking, and history of pulmonary disease were associated with a lower risk of needing mechanical ventilation and/or lower risk for mortality.

Furthermore, people with liver disease, gastrointestinal diseases, and even autoimmune diseases – which are likely associated with immunosuppression – “are not at that much of an increased risk that we noticed it in our data,” Brown said.

“As I tell many of my patients who have mild liver disease, for example, I would rather have mild liver disease and be on immunosuppressant therapy than be an older, obese male,” he added.

Assessing data for people in 38 U.S. states, and not limiting outcomes to patients in a particular COVID-19 hot spot, was a unique aspect of the research, said Brown, clinical chief of the Division of Gastroenterology and Hepatology at Weill Cornell Medicine in New York City.

Brown, lead author Michael W. Fried, MD, from TARGET PharmaSolutions in Durham, North Carolina, and colleagues studied adults from a commercially available Target Real-World Evidence (RWE) dataset of nearly 70,000 patients. They examined hospital chargemaster data and ICD-10 codes for COVID-19 inpatients between February 15 and April 20.

This population tended to be older, with 60% older than 60 years. A little more than half of participants, 53%, were men.
 

Key findings

A total of 21% of patients died after a median hospital length of stay of 8 days.

Older patients were significantly more likely to die, particularly those older than 60 years (P < .0001).

“This confirms some of the things we know about age and its impact on outcome,” Brown said.

The risk for mortality among patients older than 60 years was 7.2 times that of patients between 18 and 40 years in an adjusted multivariate analysis. The risk for death for those between 41 and 60 years of age was lower (odds ratio [OR], 2.6), compared with the youngest cohort.  

Men were more likely to die than women (OR, 1.5).

When asked if he was surprised by the high mortality rates, Brown said, “Having worked here in New York? No, I was not.”
 

Mechanical ventilation and mortality

Male sex, age older than 40 years, obesity, and presence of cardiovascular or chronic kidney disease were risk factors for mechanical ventilation.

Among the nearly 2,000 hospitalized adults requiring mechanical ventilation in the current report, only 27% were discharged alive. “The outcomes of people who are mechanically ventilated are really quite sobering,” Brown said.

People who ever required mechanical ventilation were 32 times more likely to die compared with others whose highest level of oxygenation was low-flow, high-flow, or no-oxygen therapy in an analysis that controlled for demographics and comorbidities.

Furthermore, patients placed on mechanical ventilation earlier – within 24 hours of admission – tended to experience better outcomes.
 

COVID-19 therapies?

Brown and colleagues also evaluated outcomes in patients who were taking either remdesivir or hydroxychloroquine. A total of 48 people were treated with remdesivir.

The four individuals receiving remdesivir who died were among 11 who were taking remdesivir and also on mechanical ventilation.

“The data for remdesivir is very encouraging,” Brown said.

Many more participants were treated with hydroxychloroquine, more than 4,200 or 36% of the total study population.

A higher proportion of people treated with hydroxychloroquine received mechanical ventilation, at 25%, versus 12% not treated with hydroxychloroquine.

The unadjusted mortality rate was also higher among those treated with the agent, at 25%, compared to 20% not receiving hydroxychloroquine.

The data with hydroxychloroquine can lead to two conclusions, Brown said: “One, it doesn’t work. Or two, it doesn’t work in the way that we use it.”

The researchers cautioned that their hydroxychloroquine findings must be interpreted carefully because those treated with the agent were also more likely to have comorbidities and greater COVID-19 disease severity.

“This study greatly contributes to understanding the natural course of COVID-19 infection by describing characteristics and outcomes of patients with COVID-19 hospitalized throughout the US,” the investigators note. “It identified categories of patients at greatest risk for poor outcomes, which should be used to prioritize prevention and treatment strategies in the future.”
 

Some limitations

“The findings that patients with hypertension and who were smokers had lower ventilation rates, and patients with hypertension, pulmonary disease, who were smokers had lower mortality risks was very surprising,” Ninez A. Ponce, PhD, MPP, told Medscape Medical News when asked to comment on the study.

Although the study identified multiple risk factors for ventilation and mortality, “unfortunately the dataset did not have race available or disease severity,” said Ponce, director of the UCLA Center for Health Policy Research and professor in the Department of Health Policy and Management at the UCLA Fielding School of Public Health.

“These omitted variables could have a considerable effect on the significance, magnitude, and direction of point estimates provided, so I would be cautious in interpreting the results as a picture of a nationally representative sample,” she said.

On a positive note, the study and dataset could illuminate the utility of medications used to treat COVID-19, Ponce said. In addition, as the authors note, “the data will expand over time.” 

Brown has reported receiving grants and consulting for Gilead. Ponce has disclosed no relevant financial relationships.
 

This article first appeared on Medscape.com.

With an average age of diagnosis of 28 years, and one of two incidence peaks occurring at 15-30 years, psoriasis affects many women in the midst of their reproductive years. The prospect of pregnancy – or the reality of a surprise pregnancy – drives questions about heritability of the disease in offspring, the impact of the disease on pregnancy outcomes and breastfeeding, and how to best balance risks of treatments with risks of uncontrolled psoriasis and/or psoriatic arthritis (PsA).

shironosov/Getty Images

While answers to these questions are not always clear, discussions about pregnancy and psoriasis management “shouldn’t be scary,” said Jenny E. Murase, MD, a dermatologist who speaks and writes widely about her research and experience with psoriasis and pregnancy. “We have access to information and data and educational resources to [work with] and reassure our patients – we just need to use it. Right now, there’s unnecessary suffering [with some patients unnecessarily stopping all treatment].”

Much has been learned in the past 2 decades about the course of psoriasis in pregnancy, and pregnancy outcomes data on the safety of biologics during pregnancy are increasingly emerging – particularly for tumor necrosis factor (TNF)–alpha inhibitors.

Ideally, since half of all pregnancies are unplanned, the implications of therapeutic options should be discussed with all women with psoriasis who are of reproductive age, whether they are sexually active or not. “The onus is on us to make sure that we’re considering the possibility [that our patient] could become pregnant without consulting us first,” said Dr. Murase, associate professor of dermatology at the University of California, San Francisco, and director of medical consultative dermatology for the Palo Alto Foundation Medical Group in Mountain View, Calif.

Lisa R. Sammaritano, MD, associate professor of clinical medicine at Weill Cornell Medicine and a rheumatologist at the Hospital for Special Surgery, both in New York, urges similar attention for PsA. “Pregnancy is best planned while patients have quiescent disease on pregnancy-compatible medications,” she said. “We encourage [more] rheumatologists to be actively involved in pregnancy planning [in order] to guide therapy.”

The impact of estrogen

Dr. Murase was inspired to study psoriasis and pregnancy in part by a patient she met as a medical student. “She had severe psoriasis covering her body, and she said that the only times her psoriasis cleared was during her three pregnancies,” Dr. Murase recalled. “I wondered: What about the pregnancies resulted in such a substantial reduction of her psoriasis?”

She subsequently led a study, published in 2005, of 47 pregnant and 27 nonpregnant patients with psoriasis. More than half of the patients – 55% – reported improvements in their psoriasis during pregnancy, 21% reported no change, and 23% reported worsening. Among the 16 patients who had 10% or greater psoriatic body surface area (BSA) involvement and reported improvements, lesions decreased by 84%.

In the postpartum period, only 9% reported improvement, 26% reported no change, and 65% reported worsening. The increased BSA values observed 6 weeks postpartum did not exceed those of the first trimester, suggesting a return to the patients’ baseline status.

Earlier and smaller retrospective studies had also shown that approximately half of patients improve during pregnancy, and it was believed that progesterone was most likely responsible for this improvement. Dr. Murase’s study moved the needle in that it examined BSA in pregnancy and the postpartum period. It also turned the spotlight on estrogen: Patients who had higher levels of improvement also had higher levels of estradiol, estrone, and the ratio of estrogen to progesterone. However, there was no correlation between psoriatic change and levels of progesterone.

To promote fetal survival, pregnancy triggers a shift from Th1 cell–mediated immunity – and Th17 immunity – to Th2 immunity. While there’s no proof of a causative effect, increased estrogen appears to play a role in this shift and in the reduced production of Th1 and Th17 cytokines. Psoriasis is believed to be primarily a Th17-mediated disease, with some Th1 involvement, so this down-regulation can result in improved disease status, Dr. Murase said. (A host of other autoimmune diseases categorized as Th1 mediated similarly tend to improve during pregnancy, she added.)

Information on the effect of pregnancy on PsA is “conflicting,” Dr. Sammaritano said. “Some [of a limited number of studies] suggest a beneficial effect as is generally seen for rheumatoid arthritis. Others, however, have found an increased risk of disease activity during pregnancy ... It may be that psoriatic arthritis can be quite variable from patient to patient in its clinical presentation.”

At least one study, Dr. Sammaritano added, “has shown that the arthritis in pregnancy patients with PsA did not improve, compared to control nonpregnant patients, while the psoriasis rash did improve.”

The mixed findings don’t surprise Dr. Murase. “It harder to quantify joint disease in general,” she said. “And during pregnancy, physiologic changes relating to the pregnancy itself can cause discomfort – your joints ache. The numbers [of improved] cases aren’t as high with PsA, but it’s a more complex question.”

In the postpartum period, however, research findings “all suggest an increased risk of flare” of PsA, Dr. Sammaritano said, just as with psoriasis.
 

Assessing risk of treatment

Understanding the immunologic effects of pregnancy on psoriasis and PsA – and appreciating the concept of a hormonal component – is an important part of treatment decision making. So is understanding pregnancy outcomes data.

Researchers have looked at a host of pregnancy outcomes – including congenital malformations, preterm birth, spontaneous abortion, low birth weight, macrosomia, and gestational diabetes and hypertension – in women with psoriasis or psoriasis/PsA, compared with control groups. Some studies have suggested a link between disease activity and pregnancy complications or adverse pregnancy outcomes, “just as a result of having moderate to severe disease,” while others have found no evidence of increased risk, Dr. Murase said.

“It’s a bit unclear and a difficult question to answer; it depends on what study you look at and what data you believe. It would be nice to have some clarity, but basically the jury is still out,” said Dr. Murase, who, with coauthors Alice B. Gottlieb, MD, PhD, of the department of dermatology at the Icahn School of Medicine at Mount Sinai, New York, and Caitriona Ryan, MD, of the Blackrock Clinic and Charles Institute of Dermatology, University College Dublin, discussed the pregnancy outcomes data in a recently published review of psoriasis in women.

“In my opinion, because we have therapies that are so low risk and well tolerated, it’s better to make sure that the inflammatory cascade and inflammation created by psoriasis is under control,” she said. “So whether or not the pregnancy itself causes the patient to go into remission, or whether you have to use therapy to help the patient stay in remission, it’s important to control the inflammation.”

Contraindicated in pregnancy are oral psoralen, methotrexate, and acitretin, the latter of which should be avoided for several years before pregnancy and “therefore shouldn’t be used in a woman of childbearing age,” said Dr. Murase. Methotrexate, said Dr. Sammaritano, should generally be stopped 1-3 months prior to conception.

For psoriasis, the therapy that’s “classically considered the safest in pregnancy is UVB light therapy, specifically the 300-nm wavelength of light, which works really well as an anti-inflammatory,” Dr. Murase said. Because of the potential for maternal folate degradation with phototherapy and the long-known association of folate deficiency with neural tube defects, women of childbearing age who are receiving light therapy should take daily folic acid supplementation. (She prescribes a daily prenatal vitamin containing at least 1 mg of folic acid for women who are utilizing light therapy.)

Many topical agents can be used during pregnancy, Dr. Murase said. Topical corticosteroids, she noted, have the most safety-affirming data of any topical medication.

Regarding oral therapies, Dr. Murase recommends against the use of apremilast (Otezla) for her patients. “It’s not contraindicated, but the animal studies don’t look promising, so I don’t use that one in women of childbearing age just in case. There’s just very little data to support the safety of this medication [in pregnancy].”

There are no therapeutic guidelines in the United States for guiding the management of psoriasis in women who are considering pregnancy. In 2012, the medical board of the National Psoriasis Foundation published a review of treatment options for psoriasis in pregnant or lactating women, the “closest thing to guidelines that we’ve had,” said Dr. Murase. (Now almost a decade old, the review addresses TNF inhibitors but does not cover the anti-interleukin agents more recently approved for moderate to severe psoriasis and PsA.)

For treating PsA, rheumatologists now have the American College of Rheumatology’s first guideline for the management of reproductive health in rheumatic and musculoskeletal diseases to reference. The 2020 guideline does not address PsA specifically, but its section on pregnancy and lactation includes recommendations on biologic and other therapies used to treat the disease.

Guidelines aside, physician-patient discussions over drug safety have the potential to be much more meaningful now that drug labels offer clinical summaries, data, and risk summaries regarding potential use in pregnancy. The labels have “more of a narrative, which is a more useful way to counsel patients and make risk-benefit decisions” than the former system of five-letter categories, said Dr. Murase. (The changes were made per the Pregnancy and Lactation Labeling Rule of 2015.)

MothertoBaby, a service of the nonprofit Organization of Teratology Information Specialists, also provides good evidence-based information to physicians and mothers, Dr. Sammaritano noted.

The use of biologic therapies

In a 2017 review of biologic safety for patients with psoriasis during pregnancy, Alexa B. Kimball, MD, MPH, professor of dermatology at Harvard Medical School, Boston; Martina L. Porter, MD, currently with the department of dermatology at Beth Israel Deaconess Medical Center, Boston; and Stephen J. Lockwood, MD, MPH, of the department of dermatology at Harvard Medical School, concluded that an increasing body of literature suggests that biologic agents can be used during pregnancy and breastfeeding. Anti-TNF agents “should be considered over IL-12/23 and IL-17 inhibitors due to the increased availability of long-term data,” they wrote.

“In general,” said Dr. Murase, “there’s more and more data coming out from gastroenterology and rheumatology to reassure patients and prescribing physicians that the TNF-blocker class is likely safe to use in pregnancy,” particularly during the first trimester and early second trimester, when the transport of maternal antibodies across the placenta is “essentially nonexistent.” In the third trimester, the active transport of IgG antibodies increases rapidly.

If possible, said Dr. Sammaritano, who served as lead author of the ACR’s reproductive health guideline, TNF inhibitors “will be stopped prior to the third trimester to avoid [the possibility of] high drug levels in the infant at birth, which raises concern for immunosuppression in the newborn. If disease is very active, however, they can be continued throughout the pregnancy.”

The TNF inhibitor certolizumab pegol (Cimzia) has the advantage of being transported only minimally across the placenta, if at all, she and Dr. Murase both explained. “To be actively carried across, antibodies need what’s called an Fc region for the placenta to grab onto,” Dr. Murase said. Certolizumab – a pegylated anti–binding fragment antibody – lacks this Fc region.

Two recent studies – CRIB and a UCB Pharma safety database analysis – showed “essentially no medication crossing – there were barely detectable levels,” Dr. Murase said. Certolizumab’s label contains this information and other clinical trial data as well as findings from safety database analyses/surveillance registries.

“Before we had much data for the biologics, I’d advise transitioning patients to light therapy from their biologics and a lot of times their psoriasis would improve, but it was more of a dance,” she said. “Now we tend to look at [certolizumab] when they’re of childbearing age and keep them on the treatment. I know that the baby is not being immunosuppressed.”

Consideration of the use of certolizumab when treatment with biologic agents is required throughout the pregnancy is a recommendation included in Dr. Kimball’s 2017 review.

As newer anti-interleukin agents – the IL-12/23 and IL-17 inhibitors – play a growing role in the treatment of psoriasis and PsA, questions loom about their safety profile. Dr. Murase and Dr. Sammaritano are waiting for more data. “In general,” Dr. Sammaritano said, “we recommend stopping them at the time pregnancy is detected, based on a lack of data at this time.”

Small-molecule drugs are also less well studied, she noted. “Because of their low molecular weight, we anticipate they will easily cross the placenta, so we recommend avoiding use during pregnancy until more information is available.”

Postpartum care

The good news, both experts say, is that the vast majority of medications, including biologics, are safe to use during breastfeeding. Methotrexate should be avoided, Dr. Sammaritano pointed out, and the impact of novel small-molecule therapies on breast milk has not been studied.

In her 2019 review of psoriasis in women, Dr. Murase and coauthors wrote that too many dermatologists believe that breastfeeding women should either not be on biologics or are uncertain about biologic use during breastfeeding. However, “biologics are considered compatible for use while breastfeeding due to their large molecular size and the proteolytic environment in the neonatal gastrointestinal tract,” they added.

Counseling and support for breastfeeding is especially important for women with psoriasis, Dr. Murase emphasized. “Breastfeeding is very traumatizing to the skin, and psoriasis can form in skin that’s injured. I have my patients set up an office visit very soon after the pregnancy to make sure they’re doing alright with their breastfeeding and that they’re coating their nipple area with some type of moisturizer and keeping the health of their nipples in good shape.”

Timely reviews of therapy and adjustments are also a priority, she said. “We need to prepare for 6 weeks post partum” when psoriasis will often flare without treatment.

Dr. Murase disclosed that she is a consultant for Dermira, UCB Pharma, Sanofi, Ferndale, and Regeneron. She is also coeditor in chief of the International Journal of Women’s Dermatology. Dr. Sammaritano reported that she has no disclosures relating to the treatment of PsA.

With an average age of diagnosis of 28 years, and one of two incidence peaks occurring at 15-30 years, psoriasis affects many women in the midst of their reproductive years. The prospect of pregnancy – or the reality of a surprise pregnancy – drives questions about heritability of the disease in offspring, the impact of the disease on pregnancy outcomes and breastfeeding, and how to best balance risks of treatments with risks of uncontrolled psoriasis and/or psoriatic arthritis (PsA).

shironosov/Getty Images

While answers to these questions are not always clear, discussions about pregnancy and psoriasis management “shouldn’t be scary,” said Jenny E. Murase, MD, a dermatologist who speaks and writes widely about her research and experience with psoriasis and pregnancy. “We have access to information and data and educational resources to [work with] and reassure our patients – we just need to use it. Right now, there’s unnecessary suffering [with some patients unnecessarily stopping all treatment].”

Much has been learned in the past 2 decades about the course of psoriasis in pregnancy, and pregnancy outcomes data on the safety of biologics during pregnancy are increasingly emerging – particularly for tumor necrosis factor (TNF)–alpha inhibitors.

Ideally, since half of all pregnancies are unplanned, the implications of therapeutic options should be discussed with all women with psoriasis who are of reproductive age, whether they are sexually active or not. “The onus is on us to make sure that we’re considering the possibility [that our patient] could become pregnant without consulting us first,” said Dr. Murase, associate professor of dermatology at the University of California, San Francisco, and director of medical consultative dermatology for the Palo Alto Foundation Medical Group in Mountain View, Calif.

Lisa R. Sammaritano, MD, associate professor of clinical medicine at Weill Cornell Medicine and a rheumatologist at the Hospital for Special Surgery, both in New York, urges similar attention for PsA. “Pregnancy is best planned while patients have quiescent disease on pregnancy-compatible medications,” she said. “We encourage [more] rheumatologists to be actively involved in pregnancy planning [in order] to guide therapy.”

The impact of estrogen

Dr. Murase was inspired to study psoriasis and pregnancy in part by a patient she met as a medical student. “She had severe psoriasis covering her body, and she said that the only times her psoriasis cleared was during her three pregnancies,” Dr. Murase recalled. “I wondered: What about the pregnancies resulted in such a substantial reduction of her psoriasis?”

She subsequently led a study, published in 2005, of 47 pregnant and 27 nonpregnant patients with psoriasis. More than half of the patients – 55% – reported improvements in their psoriasis during pregnancy, 21% reported no change, and 23% reported worsening. Among the 16 patients who had 10% or greater psoriatic body surface area (BSA) involvement and reported improvements, lesions decreased by 84%.

In the postpartum period, only 9% reported improvement, 26% reported no change, and 65% reported worsening. The increased BSA values observed 6 weeks postpartum did not exceed those of the first trimester, suggesting a return to the patients’ baseline status.

Earlier and smaller retrospective studies had also shown that approximately half of patients improve during pregnancy, and it was believed that progesterone was most likely responsible for this improvement. Dr. Murase’s study moved the needle in that it examined BSA in pregnancy and the postpartum period. It also turned the spotlight on estrogen: Patients who had higher levels of improvement also had higher levels of estradiol, estrone, and the ratio of estrogen to progesterone. However, there was no correlation between psoriatic change and levels of progesterone.

To promote fetal survival, pregnancy triggers a shift from Th1 cell–mediated immunity – and Th17 immunity – to Th2 immunity. While there’s no proof of a causative effect, increased estrogen appears to play a role in this shift and in the reduced production of Th1 and Th17 cytokines. Psoriasis is believed to be primarily a Th17-mediated disease, with some Th1 involvement, so this down-regulation can result in improved disease status, Dr. Murase said. (A host of other autoimmune diseases categorized as Th1 mediated similarly tend to improve during pregnancy, she added.)

Information on the effect of pregnancy on PsA is “conflicting,” Dr. Sammaritano said. “Some [of a limited number of studies] suggest a beneficial effect as is generally seen for rheumatoid arthritis. Others, however, have found an increased risk of disease activity during pregnancy ... It may be that psoriatic arthritis can be quite variable from patient to patient in its clinical presentation.”

At least one study, Dr. Sammaritano added, “has shown that the arthritis in pregnancy patients with PsA did not improve, compared to control nonpregnant patients, while the psoriasis rash did improve.”

The mixed findings don’t surprise Dr. Murase. “It harder to quantify joint disease in general,” she said. “And during pregnancy, physiologic changes relating to the pregnancy itself can cause discomfort – your joints ache. The numbers [of improved] cases aren’t as high with PsA, but it’s a more complex question.”

In the postpartum period, however, research findings “all suggest an increased risk of flare” of PsA, Dr. Sammaritano said, just as with psoriasis.
 

Assessing risk of treatment

Understanding the immunologic effects of pregnancy on psoriasis and PsA – and appreciating the concept of a hormonal component – is an important part of treatment decision making. So is understanding pregnancy outcomes data.

Researchers have looked at a host of pregnancy outcomes – including congenital malformations, preterm birth, spontaneous abortion, low birth weight, macrosomia, and gestational diabetes and hypertension – in women with psoriasis or psoriasis/PsA, compared with control groups. Some studies have suggested a link between disease activity and pregnancy complications or adverse pregnancy outcomes, “just as a result of having moderate to severe disease,” while others have found no evidence of increased risk, Dr. Murase said.

“It’s a bit unclear and a difficult question to answer; it depends on what study you look at and what data you believe. It would be nice to have some clarity, but basically the jury is still out,” said Dr. Murase, who, with coauthors Alice B. Gottlieb, MD, PhD, of the department of dermatology at the Icahn School of Medicine at Mount Sinai, New York, and Caitriona Ryan, MD, of the Blackrock Clinic and Charles Institute of Dermatology, University College Dublin, discussed the pregnancy outcomes data in a recently published review of psoriasis in women.

“In my opinion, because we have therapies that are so low risk and well tolerated, it’s better to make sure that the inflammatory cascade and inflammation created by psoriasis is under control,” she said. “So whether or not the pregnancy itself causes the patient to go into remission, or whether you have to use therapy to help the patient stay in remission, it’s important to control the inflammation.”

Contraindicated in pregnancy are oral psoralen, methotrexate, and acitretin, the latter of which should be avoided for several years before pregnancy and “therefore shouldn’t be used in a woman of childbearing age,” said Dr. Murase. Methotrexate, said Dr. Sammaritano, should generally be stopped 1-3 months prior to conception.

For psoriasis, the therapy that’s “classically considered the safest in pregnancy is UVB light therapy, specifically the 300-nm wavelength of light, which works really well as an anti-inflammatory,” Dr. Murase said. Because of the potential for maternal folate degradation with phototherapy and the long-known association of folate deficiency with neural tube defects, women of childbearing age who are receiving light therapy should take daily folic acid supplementation. (She prescribes a daily prenatal vitamin containing at least 1 mg of folic acid for women who are utilizing light therapy.)

Many topical agents can be used during pregnancy, Dr. Murase said. Topical corticosteroids, she noted, have the most safety-affirming data of any topical medication.

Regarding oral therapies, Dr. Murase recommends against the use of apremilast (Otezla) for her patients. “It’s not contraindicated, but the animal studies don’t look promising, so I don’t use that one in women of childbearing age just in case. There’s just very little data to support the safety of this medication [in pregnancy].”

There are no therapeutic guidelines in the United States for guiding the management of psoriasis in women who are considering pregnancy. In 2012, the medical board of the National Psoriasis Foundation published a review of treatment options for psoriasis in pregnant or lactating women, the “closest thing to guidelines that we’ve had,” said Dr. Murase. (Now almost a decade old, the review addresses TNF inhibitors but does not cover the anti-interleukin agents more recently approved for moderate to severe psoriasis and PsA.)

For treating PsA, rheumatologists now have the American College of Rheumatology’s first guideline for the management of reproductive health in rheumatic and musculoskeletal diseases to reference. The 2020 guideline does not address PsA specifically, but its section on pregnancy and lactation includes recommendations on biologic and other therapies used to treat the disease.

Guidelines aside, physician-patient discussions over drug safety have the potential to be much more meaningful now that drug labels offer clinical summaries, data, and risk summaries regarding potential use in pregnancy. The labels have “more of a narrative, which is a more useful way to counsel patients and make risk-benefit decisions” than the former system of five-letter categories, said Dr. Murase. (The changes were made per the Pregnancy and Lactation Labeling Rule of 2015.)

MothertoBaby, a service of the nonprofit Organization of Teratology Information Specialists, also provides good evidence-based information to physicians and mothers, Dr. Sammaritano noted.

The use of biologic therapies

In a 2017 review of biologic safety for patients with psoriasis during pregnancy, Alexa B. Kimball, MD, MPH, professor of dermatology at Harvard Medical School, Boston; Martina L. Porter, MD, currently with the department of dermatology at Beth Israel Deaconess Medical Center, Boston; and Stephen J. Lockwood, MD, MPH, of the department of dermatology at Harvard Medical School, concluded that an increasing body of literature suggests that biologic agents can be used during pregnancy and breastfeeding. Anti-TNF agents “should be considered over IL-12/23 and IL-17 inhibitors due to the increased availability of long-term data,” they wrote.

“In general,” said Dr. Murase, “there’s more and more data coming out from gastroenterology and rheumatology to reassure patients and prescribing physicians that the TNF-blocker class is likely safe to use in pregnancy,” particularly during the first trimester and early second trimester, when the transport of maternal antibodies across the placenta is “essentially nonexistent.” In the third trimester, the active transport of IgG antibodies increases rapidly.

If possible, said Dr. Sammaritano, who served as lead author of the ACR’s reproductive health guideline, TNF inhibitors “will be stopped prior to the third trimester to avoid [the possibility of] high drug levels in the infant at birth, which raises concern for immunosuppression in the newborn. If disease is very active, however, they can be continued throughout the pregnancy.”

The TNF inhibitor certolizumab pegol (Cimzia) has the advantage of being transported only minimally across the placenta, if at all, she and Dr. Murase both explained. “To be actively carried across, antibodies need what’s called an Fc region for the placenta to grab onto,” Dr. Murase said. Certolizumab – a pegylated anti–binding fragment antibody – lacks this Fc region.

Two recent studies – CRIB and a UCB Pharma safety database analysis – showed “essentially no medication crossing – there were barely detectable levels,” Dr. Murase said. Certolizumab’s label contains this information and other clinical trial data as well as findings from safety database analyses/surveillance registries.

“Before we had much data for the biologics, I’d advise transitioning patients to light therapy from their biologics and a lot of times their psoriasis would improve, but it was more of a dance,” she said. “Now we tend to look at [certolizumab] when they’re of childbearing age and keep them on the treatment. I know that the baby is not being immunosuppressed.”

Consideration of the use of certolizumab when treatment with biologic agents is required throughout the pregnancy is a recommendation included in Dr. Kimball’s 2017 review.

As newer anti-interleukin agents – the IL-12/23 and IL-17 inhibitors – play a growing role in the treatment of psoriasis and PsA, questions loom about their safety profile. Dr. Murase and Dr. Sammaritano are waiting for more data. “In general,” Dr. Sammaritano said, “we recommend stopping them at the time pregnancy is detected, based on a lack of data at this time.”

Small-molecule drugs are also less well studied, she noted. “Because of their low molecular weight, we anticipate they will easily cross the placenta, so we recommend avoiding use during pregnancy until more information is available.”

Postpartum care

The good news, both experts say, is that the vast majority of medications, including biologics, are safe to use during breastfeeding. Methotrexate should be avoided, Dr. Sammaritano pointed out, and the impact of novel small-molecule therapies on breast milk has not been studied.

In her 2019 review of psoriasis in women, Dr. Murase and coauthors wrote that too many dermatologists believe that breastfeeding women should either not be on biologics or are uncertain about biologic use during breastfeeding. However, “biologics are considered compatible for use while breastfeeding due to their large molecular size and the proteolytic environment in the neonatal gastrointestinal tract,” they added.

Counseling and support for breastfeeding is especially important for women with psoriasis, Dr. Murase emphasized. “Breastfeeding is very traumatizing to the skin, and psoriasis can form in skin that’s injured. I have my patients set up an office visit very soon after the pregnancy to make sure they’re doing alright with their breastfeeding and that they’re coating their nipple area with some type of moisturizer and keeping the health of their nipples in good shape.”

Timely reviews of therapy and adjustments are also a priority, she said. “We need to prepare for 6 weeks post partum” when psoriasis will often flare without treatment.

Dr. Murase disclosed that she is a consultant for Dermira, UCB Pharma, Sanofi, Ferndale, and Regeneron. She is also coeditor in chief of the International Journal of Women’s Dermatology. Dr. Sammaritano reported that she has no disclosures relating to the treatment of PsA.

With an average age of diagnosis of 28 years, and one of two incidence peaks occurring at 15-30 years, psoriasis affects many women in the midst of their reproductive years. The prospect of pregnancy – or the reality of a surprise pregnancy – drives questions about heritability of the disease in offspring, the impact of the disease on pregnancy outcomes and breastfeeding, and how to best balance risks of treatments with risks of uncontrolled psoriasis and/or psoriatic arthritis (PsA).

shironosov/Getty Images

While answers to these questions are not always clear, discussions about pregnancy and psoriasis management “shouldn’t be scary,” said Jenny E. Murase, MD, a dermatologist who speaks and writes widely about her research and experience with psoriasis and pregnancy. “We have access to information and data and educational resources to [work with] and reassure our patients – we just need to use it. Right now, there’s unnecessary suffering [with some patients unnecessarily stopping all treatment].”

Much has been learned in the past 2 decades about the course of psoriasis in pregnancy, and pregnancy outcomes data on the safety of biologics during pregnancy are increasingly emerging – particularly for tumor necrosis factor (TNF)–alpha inhibitors.

Ideally, since half of all pregnancies are unplanned, the implications of therapeutic options should be discussed with all women with psoriasis who are of reproductive age, whether they are sexually active or not. “The onus is on us to make sure that we’re considering the possibility [that our patient] could become pregnant without consulting us first,” said Dr. Murase, associate professor of dermatology at the University of California, San Francisco, and director of medical consultative dermatology for the Palo Alto Foundation Medical Group in Mountain View, Calif.

Lisa R. Sammaritano, MD, associate professor of clinical medicine at Weill Cornell Medicine and a rheumatologist at the Hospital for Special Surgery, both in New York, urges similar attention for PsA. “Pregnancy is best planned while patients have quiescent disease on pregnancy-compatible medications,” she said. “We encourage [more] rheumatologists to be actively involved in pregnancy planning [in order] to guide therapy.”

The impact of estrogen

Dr. Murase was inspired to study psoriasis and pregnancy in part by a patient she met as a medical student. “She had severe psoriasis covering her body, and she said that the only times her psoriasis cleared was during her three pregnancies,” Dr. Murase recalled. “I wondered: What about the pregnancies resulted in such a substantial reduction of her psoriasis?”

She subsequently led a study, published in 2005, of 47 pregnant and 27 nonpregnant patients with psoriasis. More than half of the patients – 55% – reported improvements in their psoriasis during pregnancy, 21% reported no change, and 23% reported worsening. Among the 16 patients who had 10% or greater psoriatic body surface area (BSA) involvement and reported improvements, lesions decreased by 84%.

In the postpartum period, only 9% reported improvement, 26% reported no change, and 65% reported worsening. The increased BSA values observed 6 weeks postpartum did not exceed those of the first trimester, suggesting a return to the patients’ baseline status.

Earlier and smaller retrospective studies had also shown that approximately half of patients improve during pregnancy, and it was believed that progesterone was most likely responsible for this improvement. Dr. Murase’s study moved the needle in that it examined BSA in pregnancy and the postpartum period. It also turned the spotlight on estrogen: Patients who had higher levels of improvement also had higher levels of estradiol, estrone, and the ratio of estrogen to progesterone. However, there was no correlation between psoriatic change and levels of progesterone.

To promote fetal survival, pregnancy triggers a shift from Th1 cell–mediated immunity – and Th17 immunity – to Th2 immunity. While there’s no proof of a causative effect, increased estrogen appears to play a role in this shift and in the reduced production of Th1 and Th17 cytokines. Psoriasis is believed to be primarily a Th17-mediated disease, with some Th1 involvement, so this down-regulation can result in improved disease status, Dr. Murase said. (A host of other autoimmune diseases categorized as Th1 mediated similarly tend to improve during pregnancy, she added.)

Information on the effect of pregnancy on PsA is “conflicting,” Dr. Sammaritano said. “Some [of a limited number of studies] suggest a beneficial effect as is generally seen for rheumatoid arthritis. Others, however, have found an increased risk of disease activity during pregnancy ... It may be that psoriatic arthritis can be quite variable from patient to patient in its clinical presentation.”

At least one study, Dr. Sammaritano added, “has shown that the arthritis in pregnancy patients with PsA did not improve, compared to control nonpregnant patients, while the psoriasis rash did improve.”

The mixed findings don’t surprise Dr. Murase. “It harder to quantify joint disease in general,” she said. “And during pregnancy, physiologic changes relating to the pregnancy itself can cause discomfort – your joints ache. The numbers [of improved] cases aren’t as high with PsA, but it’s a more complex question.”

In the postpartum period, however, research findings “all suggest an increased risk of flare” of PsA, Dr. Sammaritano said, just as with psoriasis.
 

Assessing risk of treatment

Understanding the immunologic effects of pregnancy on psoriasis and PsA – and appreciating the concept of a hormonal component – is an important part of treatment decision making. So is understanding pregnancy outcomes data.

Researchers have looked at a host of pregnancy outcomes – including congenital malformations, preterm birth, spontaneous abortion, low birth weight, macrosomia, and gestational diabetes and hypertension – in women with psoriasis or psoriasis/PsA, compared with control groups. Some studies have suggested a link between disease activity and pregnancy complications or adverse pregnancy outcomes, “just as a result of having moderate to severe disease,” while others have found no evidence of increased risk, Dr. Murase said.

“It’s a bit unclear and a difficult question to answer; it depends on what study you look at and what data you believe. It would be nice to have some clarity, but basically the jury is still out,” said Dr. Murase, who, with coauthors Alice B. Gottlieb, MD, PhD, of the department of dermatology at the Icahn School of Medicine at Mount Sinai, New York, and Caitriona Ryan, MD, of the Blackrock Clinic and Charles Institute of Dermatology, University College Dublin, discussed the pregnancy outcomes data in a recently published review of psoriasis in women.

“In my opinion, because we have therapies that are so low risk and well tolerated, it’s better to make sure that the inflammatory cascade and inflammation created by psoriasis is under control,” she said. “So whether or not the pregnancy itself causes the patient to go into remission, or whether you have to use therapy to help the patient stay in remission, it’s important to control the inflammation.”

Contraindicated in pregnancy are oral psoralen, methotrexate, and acitretin, the latter of which should be avoided for several years before pregnancy and “therefore shouldn’t be used in a woman of childbearing age,” said Dr. Murase. Methotrexate, said Dr. Sammaritano, should generally be stopped 1-3 months prior to conception.

For psoriasis, the therapy that’s “classically considered the safest in pregnancy is UVB light therapy, specifically the 300-nm wavelength of light, which works really well as an anti-inflammatory,” Dr. Murase said. Because of the potential for maternal folate degradation with phototherapy and the long-known association of folate deficiency with neural tube defects, women of childbearing age who are receiving light therapy should take daily folic acid supplementation. (She prescribes a daily prenatal vitamin containing at least 1 mg of folic acid for women who are utilizing light therapy.)

Many topical agents can be used during pregnancy, Dr. Murase said. Topical corticosteroids, she noted, have the most safety-affirming data of any topical medication.

Regarding oral therapies, Dr. Murase recommends against the use of apremilast (Otezla) for her patients. “It’s not contraindicated, but the animal studies don’t look promising, so I don’t use that one in women of childbearing age just in case. There’s just very little data to support the safety of this medication [in pregnancy].”

There are no therapeutic guidelines in the United States for guiding the management of psoriasis in women who are considering pregnancy. In 2012, the medical board of the National Psoriasis Foundation published a review of treatment options for psoriasis in pregnant or lactating women, the “closest thing to guidelines that we’ve had,” said Dr. Murase. (Now almost a decade old, the review addresses TNF inhibitors but does not cover the anti-interleukin agents more recently approved for moderate to severe psoriasis and PsA.)

For treating PsA, rheumatologists now have the American College of Rheumatology’s first guideline for the management of reproductive health in rheumatic and musculoskeletal diseases to reference. The 2020 guideline does not address PsA specifically, but its section on pregnancy and lactation includes recommendations on biologic and other therapies used to treat the disease.

Guidelines aside, physician-patient discussions over drug safety have the potential to be much more meaningful now that drug labels offer clinical summaries, data, and risk summaries regarding potential use in pregnancy. The labels have “more of a narrative, which is a more useful way to counsel patients and make risk-benefit decisions” than the former system of five-letter categories, said Dr. Murase. (The changes were made per the Pregnancy and Lactation Labeling Rule of 2015.)

MothertoBaby, a service of the nonprofit Organization of Teratology Information Specialists, also provides good evidence-based information to physicians and mothers, Dr. Sammaritano noted.

The use of biologic therapies

In a 2017 review of biologic safety for patients with psoriasis during pregnancy, Alexa B. Kimball, MD, MPH, professor of dermatology at Harvard Medical School, Boston; Martina L. Porter, MD, currently with the department of dermatology at Beth Israel Deaconess Medical Center, Boston; and Stephen J. Lockwood, MD, MPH, of the department of dermatology at Harvard Medical School, concluded that an increasing body of literature suggests that biologic agents can be used during pregnancy and breastfeeding. Anti-TNF agents “should be considered over IL-12/23 and IL-17 inhibitors due to the increased availability of long-term data,” they wrote.

“In general,” said Dr. Murase, “there’s more and more data coming out from gastroenterology and rheumatology to reassure patients and prescribing physicians that the TNF-blocker class is likely safe to use in pregnancy,” particularly during the first trimester and early second trimester, when the transport of maternal antibodies across the placenta is “essentially nonexistent.” In the third trimester, the active transport of IgG antibodies increases rapidly.

If possible, said Dr. Sammaritano, who served as lead author of the ACR’s reproductive health guideline, TNF inhibitors “will be stopped prior to the third trimester to avoid [the possibility of] high drug levels in the infant at birth, which raises concern for immunosuppression in the newborn. If disease is very active, however, they can be continued throughout the pregnancy.”

The TNF inhibitor certolizumab pegol (Cimzia) has the advantage of being transported only minimally across the placenta, if at all, she and Dr. Murase both explained. “To be actively carried across, antibodies need what’s called an Fc region for the placenta to grab onto,” Dr. Murase said. Certolizumab – a pegylated anti–binding fragment antibody – lacks this Fc region.

Two recent studies – CRIB and a UCB Pharma safety database analysis – showed “essentially no medication crossing – there were barely detectable levels,” Dr. Murase said. Certolizumab’s label contains this information and other clinical trial data as well as findings from safety database analyses/surveillance registries.

“Before we had much data for the biologics, I’d advise transitioning patients to light therapy from their biologics and a lot of times their psoriasis would improve, but it was more of a dance,” she said. “Now we tend to look at [certolizumab] when they’re of childbearing age and keep them on the treatment. I know that the baby is not being immunosuppressed.”

Consideration of the use of certolizumab when treatment with biologic agents is required throughout the pregnancy is a recommendation included in Dr. Kimball’s 2017 review.

As newer anti-interleukin agents – the IL-12/23 and IL-17 inhibitors – play a growing role in the treatment of psoriasis and PsA, questions loom about their safety profile. Dr. Murase and Dr. Sammaritano are waiting for more data. “In general,” Dr. Sammaritano said, “we recommend stopping them at the time pregnancy is detected, based on a lack of data at this time.”

Small-molecule drugs are also less well studied, she noted. “Because of their low molecular weight, we anticipate they will easily cross the placenta, so we recommend avoiding use during pregnancy until more information is available.”

Postpartum care

The good news, both experts say, is that the vast majority of medications, including biologics, are safe to use during breastfeeding. Methotrexate should be avoided, Dr. Sammaritano pointed out, and the impact of novel small-molecule therapies on breast milk has not been studied.

In her 2019 review of psoriasis in women, Dr. Murase and coauthors wrote that too many dermatologists believe that breastfeeding women should either not be on biologics or are uncertain about biologic use during breastfeeding. However, “biologics are considered compatible for use while breastfeeding due to their large molecular size and the proteolytic environment in the neonatal gastrointestinal tract,” they added.

Counseling and support for breastfeeding is especially important for women with psoriasis, Dr. Murase emphasized. “Breastfeeding is very traumatizing to the skin, and psoriasis can form in skin that’s injured. I have my patients set up an office visit very soon after the pregnancy to make sure they’re doing alright with their breastfeeding and that they’re coating their nipple area with some type of moisturizer and keeping the health of their nipples in good shape.”

Timely reviews of therapy and adjustments are also a priority, she said. “We need to prepare for 6 weeks post partum” when psoriasis will often flare without treatment.

Dr. Murase disclosed that she is a consultant for Dermira, UCB Pharma, Sanofi, Ferndale, and Regeneron. She is also coeditor in chief of the International Journal of Women’s Dermatology. Dr. Sammaritano reported that she has no disclosures relating to the treatment of PsA.

The first randomized study to compare continuing versus stopping ACE inhibitors or angiotensin receptor blockers (ARBs) for patients with COVID-19 has shown no difference in key outcomes between the two approaches.

European Society of Cardiology

The BRACE CORONA trial – conducted in patients had been taking an ACE inhibitor or an ARB on a long-term basis and who were subsequently hospitalized with COVID-19 – showed no difference in the primary endpoint of number of days alive and out of hospital among those whose medication was suspended for 30 days and those who continued undergoing treatment with these agents.

“Because these data indicate that there is no clinical benefit from routinely interrupting these medications in hospitalized patients with mild to moderate COVID-19, they should generally be continued for those with an indication,” principal investigator Renato Lopes, MD, of Duke Clinical Research Institute, Durham, N.C., concluded.

The BRACE CORONA trial was presented at the European Society of Cardiology Congress 2020 on Sept. 1.

Dr. Lopes explained that there are two conflicting hypotheses about the role of ACE inhibitors and ARBs in COVID-19.

One hypothesis suggests that use of these drugs could be harmful by increasing the expression of ACE2 receptors (which the SARS-CoV-2 virus uses to gain entry into cells), thus potentially enhancing viral binding and viral entry. The other suggests that ACE inhibitors and ARBs could be protective by reducing production of angiotensin II and enhancing the generation of angiotensin 1-7, which attenuates inflammation and fibrosis and therefore could attenuate lung injury.

The BRACE CORONA trial was an academic-led randomized study that tested two strategies: temporarily stopping the ACE inhibitor/ARB for 30 days or continuing these drugs for patients who had been taking these medications on a long-term basis and were hospitalized with a confirmed diagnosis of COVID-19.

The primary outcome was the number of days alive and out of hospital at 30 days. Patients who were using more than three antihypertensive drugs or sacubitril/valsartan or who were hemodynamically unstable at presentation were excluded from the study.

The trial enrolled 659 patients from 29 sites in Brazil. The mean age of patients was 56 years, 40% were women, and 52% were obese. ACE inhibitors were being taken by 15% of the trial participants; ARBs were being taken by 85%. The median duration of ACE inhibitor/ARB treatment was 5 years.

Patients were a median of 6 days from COVID-19 symptom onset. For 30% of the patients, oxygen saturation was below 94% at entry. In terms of COVID-19 symptoms, 57% were classified as mild, and 43% as moderate.

Those with severe COVID-19 symptoms who needed intubation or vasoactive drugs were excluded. Antihypertensive therapy would generally be discontinued in these patients anyway, Dr. Lopes said.

Results showed that the average number of days alive and out of hospital was 21.9 days for patients who stopped taking ACE inhibitors/ARBs and 22.9 days for patients who continued taking these medications. The average difference between groups was –1.1 days.

The average ratio of days alive and out of hospital between the suspending and continuing groups was 0.95 (95% CI, 0.90-1.01; P = .09).

The proportion of patients alive and out of hospital by the end of 30 days in the suspending ACE inhibitor/ARB group was 91.8% versus 95% in the continuing group.

A similar 30-day mortality rate was seen for patients who continued and those who suspended ACE inhibitor/ARB therapy, at 2.8% and 2.7%, respectively (hazard ratio, 0.97). The median number of days that patients were alive and out of hospital was 25 in both groups.

Dr. Lopes said that there was no difference between the two groups with regard to many other secondary outcomes. These included COVID-19 disease progression (need for intubation, ventilation, need for vasoactive drugs, or imaging results) and cardiovascular endpoints (MI, stroke, thromboembolic events, worsening heart failure, myocarditis, or hypertensive crisis).

“Our results endorse with reliable and more definitive data what most medical and cardiovascular societies are recommending – that patients do not stop ACE inhibitor or ARB medication. This has been based on observational data so far, but BRACE CORONA now provides randomized data to support this recommendation,” Dr. Lopes concluded.

Dr. Lopes noted that several subgroups had been prespecified for analysis. Factors included age, obesity, difference between ACE inhibitors/ARBs, difference in oxygen saturation at presentation, time since COVID-19 symptom onset, degree of lung involvement on CT, and symptom severity on presentation.

“We saw very consistent effects of our main findings across all these subgroups, and we plan to report more details of these in the near future,” he said.
 

Protective for older patients?

The discussant of the study at the ESC Hotline session, Gianfranco Parati, MD, University of Milan-Bicocca and San Luca Hospital, Milan, congratulated Lopes and his team for conducting this important trial at such a difficult time.

He pointed out that patients in the BRACE CORONA trial were quite young (average age, 56 years) and that observational data so far suggest that ACE inhibitors and ARBs have a stronger protective effect in older COVID-19 patients.

He also noted that the percentage of patients alive and out of hospital at 30 days was higher for the patients who continued on treatment in this study (95% vs. 91.8%), which suggested an advantage in maintaining the medication.

Dr. Lopes replied that one-quarter of the population in the BRACE CORONA trial was older than 65 years, which he said was a “reasonable number.”

“Subgroup analysis by age did not show a significant interaction, but the effect of continuing treatment does seem to be more favorable in older patients and also in those who were sicker and had more comorbidities,” he added.

Dr. Parati also suggested that it would have been difficult to discern differences between ACE inhibitors and ARBs in the BRACE CORONA trial, because so few patents were taking ACE inhibitors; the follow-up period of 30 days was relatively short, inasmuch as these drugs may have long-term effects; and it would have been difficult to show differences in the main outcomes used in the study – mortality and time out of hospital – in these patients with mild to moderate disease.

Franz H. Messerli, MD, and Christoph Gräni, MD, University of Bern (Switzerland), said in a joint statement: “The BRACE CORONA trial provides answers to what we know from retrospective studies: if you have already COVID, don’t stop renin-angiotensin system blocker medication.”

But they added that the study does not answer the question about the risk/benefit of ACE inhibitors or ARBs with regard to possible enhanced viral entry through the ACE2 receptor. “What about all those on these drugs who are not infected with COVID? Do they need to stop them? We simply don’t know yet,” they said.

Dr. Messerli and Dr. Gräni added that they would like to see a study that compared patients before SARS-CoV-2 infection who were without hypertension, patients with hypertension who were taking ACE inhibitors or ARBs, and patients with hypertension taking other antihypertensive drugs.

The BRACE CORONA trial was sponsored by D’Or Institute for Research and Education and the Brazilian Clinical Research Institute. Dr. Lopes has disclosed no relevant financial relationships.

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

The first randomized study to compare continuing versus stopping ACE inhibitors or angiotensin receptor blockers (ARBs) for patients with COVID-19 has shown no difference in key outcomes between the two approaches.

European Society of Cardiology

The BRACE CORONA trial – conducted in patients had been taking an ACE inhibitor or an ARB on a long-term basis and who were subsequently hospitalized with COVID-19 – showed no difference in the primary endpoint of number of days alive and out of hospital among those whose medication was suspended for 30 days and those who continued undergoing treatment with these agents.

“Because these data indicate that there is no clinical benefit from routinely interrupting these medications in hospitalized patients with mild to moderate COVID-19, they should generally be continued for those with an indication,” principal investigator Renato Lopes, MD, of Duke Clinical Research Institute, Durham, N.C., concluded.

The BRACE CORONA trial was presented at the European Society of Cardiology Congress 2020 on Sept. 1.

Dr. Lopes explained that there are two conflicting hypotheses about the role of ACE inhibitors and ARBs in COVID-19.

One hypothesis suggests that use of these drugs could be harmful by increasing the expression of ACE2 receptors (which the SARS-CoV-2 virus uses to gain entry into cells), thus potentially enhancing viral binding and viral entry. The other suggests that ACE inhibitors and ARBs could be protective by reducing production of angiotensin II and enhancing the generation of angiotensin 1-7, which attenuates inflammation and fibrosis and therefore could attenuate lung injury.

The BRACE CORONA trial was an academic-led randomized study that tested two strategies: temporarily stopping the ACE inhibitor/ARB for 30 days or continuing these drugs for patients who had been taking these medications on a long-term basis and were hospitalized with a confirmed diagnosis of COVID-19.

The primary outcome was the number of days alive and out of hospital at 30 days. Patients who were using more than three antihypertensive drugs or sacubitril/valsartan or who were hemodynamically unstable at presentation were excluded from the study.

The trial enrolled 659 patients from 29 sites in Brazil. The mean age of patients was 56 years, 40% were women, and 52% were obese. ACE inhibitors were being taken by 15% of the trial participants; ARBs were being taken by 85%. The median duration of ACE inhibitor/ARB treatment was 5 years.

Patients were a median of 6 days from COVID-19 symptom onset. For 30% of the patients, oxygen saturation was below 94% at entry. In terms of COVID-19 symptoms, 57% were classified as mild, and 43% as moderate.

Those with severe COVID-19 symptoms who needed intubation or vasoactive drugs were excluded. Antihypertensive therapy would generally be discontinued in these patients anyway, Dr. Lopes said.

Results showed that the average number of days alive and out of hospital was 21.9 days for patients who stopped taking ACE inhibitors/ARBs and 22.9 days for patients who continued taking these medications. The average difference between groups was –1.1 days.

The average ratio of days alive and out of hospital between the suspending and continuing groups was 0.95 (95% CI, 0.90-1.01; P = .09).

The proportion of patients alive and out of hospital by the end of 30 days in the suspending ACE inhibitor/ARB group was 91.8% versus 95% in the continuing group.

A similar 30-day mortality rate was seen for patients who continued and those who suspended ACE inhibitor/ARB therapy, at 2.8% and 2.7%, respectively (hazard ratio, 0.97). The median number of days that patients were alive and out of hospital was 25 in both groups.

Dr. Lopes said that there was no difference between the two groups with regard to many other secondary outcomes. These included COVID-19 disease progression (need for intubation, ventilation, need for vasoactive drugs, or imaging results) and cardiovascular endpoints (MI, stroke, thromboembolic events, worsening heart failure, myocarditis, or hypertensive crisis).

“Our results endorse with reliable and more definitive data what most medical and cardiovascular societies are recommending – that patients do not stop ACE inhibitor or ARB medication. This has been based on observational data so far, but BRACE CORONA now provides randomized data to support this recommendation,” Dr. Lopes concluded.

Dr. Lopes noted that several subgroups had been prespecified for analysis. Factors included age, obesity, difference between ACE inhibitors/ARBs, difference in oxygen saturation at presentation, time since COVID-19 symptom onset, degree of lung involvement on CT, and symptom severity on presentation.

“We saw very consistent effects of our main findings across all these subgroups, and we plan to report more details of these in the near future,” he said.
 

Protective for older patients?

The discussant of the study at the ESC Hotline session, Gianfranco Parati, MD, University of Milan-Bicocca and San Luca Hospital, Milan, congratulated Lopes and his team for conducting this important trial at such a difficult time.

He pointed out that patients in the BRACE CORONA trial were quite young (average age, 56 years) and that observational data so far suggest that ACE inhibitors and ARBs have a stronger protective effect in older COVID-19 patients.

He also noted that the percentage of patients alive and out of hospital at 30 days was higher for the patients who continued on treatment in this study (95% vs. 91.8%), which suggested an advantage in maintaining the medication.

Dr. Lopes replied that one-quarter of the population in the BRACE CORONA trial was older than 65 years, which he said was a “reasonable number.”

“Subgroup analysis by age did not show a significant interaction, but the effect of continuing treatment does seem to be more favorable in older patients and also in those who were sicker and had more comorbidities,” he added.

Dr. Parati also suggested that it would have been difficult to discern differences between ACE inhibitors and ARBs in the BRACE CORONA trial, because so few patents were taking ACE inhibitors; the follow-up period of 30 days was relatively short, inasmuch as these drugs may have long-term effects; and it would have been difficult to show differences in the main outcomes used in the study – mortality and time out of hospital – in these patients with mild to moderate disease.

Franz H. Messerli, MD, and Christoph Gräni, MD, University of Bern (Switzerland), said in a joint statement: “The BRACE CORONA trial provides answers to what we know from retrospective studies: if you have already COVID, don’t stop renin-angiotensin system blocker medication.”

But they added that the study does not answer the question about the risk/benefit of ACE inhibitors or ARBs with regard to possible enhanced viral entry through the ACE2 receptor. “What about all those on these drugs who are not infected with COVID? Do they need to stop them? We simply don’t know yet,” they said.

Dr. Messerli and Dr. Gräni added that they would like to see a study that compared patients before SARS-CoV-2 infection who were without hypertension, patients with hypertension who were taking ACE inhibitors or ARBs, and patients with hypertension taking other antihypertensive drugs.

The BRACE CORONA trial was sponsored by D’Or Institute for Research and Education and the Brazilian Clinical Research Institute. Dr. Lopes has disclosed no relevant financial relationships.

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

The first randomized study to compare continuing versus stopping ACE inhibitors or angiotensin receptor blockers (ARBs) for patients with COVID-19 has shown no difference in key outcomes between the two approaches.

European Society of Cardiology

The BRACE CORONA trial – conducted in patients had been taking an ACE inhibitor or an ARB on a long-term basis and who were subsequently hospitalized with COVID-19 – showed no difference in the primary endpoint of number of days alive and out of hospital among those whose medication was suspended for 30 days and those who continued undergoing treatment with these agents.

“Because these data indicate that there is no clinical benefit from routinely interrupting these medications in hospitalized patients with mild to moderate COVID-19, they should generally be continued for those with an indication,” principal investigator Renato Lopes, MD, of Duke Clinical Research Institute, Durham, N.C., concluded.

The BRACE CORONA trial was presented at the European Society of Cardiology Congress 2020 on Sept. 1.

Dr. Lopes explained that there are two conflicting hypotheses about the role of ACE inhibitors and ARBs in COVID-19.

One hypothesis suggests that use of these drugs could be harmful by increasing the expression of ACE2 receptors (which the SARS-CoV-2 virus uses to gain entry into cells), thus potentially enhancing viral binding and viral entry. The other suggests that ACE inhibitors and ARBs could be protective by reducing production of angiotensin II and enhancing the generation of angiotensin 1-7, which attenuates inflammation and fibrosis and therefore could attenuate lung injury.

The BRACE CORONA trial was an academic-led randomized study that tested two strategies: temporarily stopping the ACE inhibitor/ARB for 30 days or continuing these drugs for patients who had been taking these medications on a long-term basis and were hospitalized with a confirmed diagnosis of COVID-19.

The primary outcome was the number of days alive and out of hospital at 30 days. Patients who were using more than three antihypertensive drugs or sacubitril/valsartan or who were hemodynamically unstable at presentation were excluded from the study.

The trial enrolled 659 patients from 29 sites in Brazil. The mean age of patients was 56 years, 40% were women, and 52% were obese. ACE inhibitors were being taken by 15% of the trial participants; ARBs were being taken by 85%. The median duration of ACE inhibitor/ARB treatment was 5 years.

Patients were a median of 6 days from COVID-19 symptom onset. For 30% of the patients, oxygen saturation was below 94% at entry. In terms of COVID-19 symptoms, 57% were classified as mild, and 43% as moderate.

Those with severe COVID-19 symptoms who needed intubation or vasoactive drugs were excluded. Antihypertensive therapy would generally be discontinued in these patients anyway, Dr. Lopes said.

Results showed that the average number of days alive and out of hospital was 21.9 days for patients who stopped taking ACE inhibitors/ARBs and 22.9 days for patients who continued taking these medications. The average difference between groups was –1.1 days.

The average ratio of days alive and out of hospital between the suspending and continuing groups was 0.95 (95% CI, 0.90-1.01; P = .09).

The proportion of patients alive and out of hospital by the end of 30 days in the suspending ACE inhibitor/ARB group was 91.8% versus 95% in the continuing group.

A similar 30-day mortality rate was seen for patients who continued and those who suspended ACE inhibitor/ARB therapy, at 2.8% and 2.7%, respectively (hazard ratio, 0.97). The median number of days that patients were alive and out of hospital was 25 in both groups.

Dr. Lopes said that there was no difference between the two groups with regard to many other secondary outcomes. These included COVID-19 disease progression (need for intubation, ventilation, need for vasoactive drugs, or imaging results) and cardiovascular endpoints (MI, stroke, thromboembolic events, worsening heart failure, myocarditis, or hypertensive crisis).

“Our results endorse with reliable and more definitive data what most medical and cardiovascular societies are recommending – that patients do not stop ACE inhibitor or ARB medication. This has been based on observational data so far, but BRACE CORONA now provides randomized data to support this recommendation,” Dr. Lopes concluded.

Dr. Lopes noted that several subgroups had been prespecified for analysis. Factors included age, obesity, difference between ACE inhibitors/ARBs, difference in oxygen saturation at presentation, time since COVID-19 symptom onset, degree of lung involvement on CT, and symptom severity on presentation.

“We saw very consistent effects of our main findings across all these subgroups, and we plan to report more details of these in the near future,” he said.
 

Protective for older patients?

The discussant of the study at the ESC Hotline session, Gianfranco Parati, MD, University of Milan-Bicocca and San Luca Hospital, Milan, congratulated Lopes and his team for conducting this important trial at such a difficult time.

He pointed out that patients in the BRACE CORONA trial were quite young (average age, 56 years) and that observational data so far suggest that ACE inhibitors and ARBs have a stronger protective effect in older COVID-19 patients.

He also noted that the percentage of patients alive and out of hospital at 30 days was higher for the patients who continued on treatment in this study (95% vs. 91.8%), which suggested an advantage in maintaining the medication.

Dr. Lopes replied that one-quarter of the population in the BRACE CORONA trial was older than 65 years, which he said was a “reasonable number.”

“Subgroup analysis by age did not show a significant interaction, but the effect of continuing treatment does seem to be more favorable in older patients and also in those who were sicker and had more comorbidities,” he added.

Dr. Parati also suggested that it would have been difficult to discern differences between ACE inhibitors and ARBs in the BRACE CORONA trial, because so few patents were taking ACE inhibitors; the follow-up period of 30 days was relatively short, inasmuch as these drugs may have long-term effects; and it would have been difficult to show differences in the main outcomes used in the study – mortality and time out of hospital – in these patients with mild to moderate disease.

Franz H. Messerli, MD, and Christoph Gräni, MD, University of Bern (Switzerland), said in a joint statement: “The BRACE CORONA trial provides answers to what we know from retrospective studies: if you have already COVID, don’t stop renin-angiotensin system blocker medication.”

But they added that the study does not answer the question about the risk/benefit of ACE inhibitors or ARBs with regard to possible enhanced viral entry through the ACE2 receptor. “What about all those on these drugs who are not infected with COVID? Do they need to stop them? We simply don’t know yet,” they said.

Dr. Messerli and Dr. Gräni added that they would like to see a study that compared patients before SARS-CoV-2 infection who were without hypertension, patients with hypertension who were taking ACE inhibitors or ARBs, and patients with hypertension taking other antihypertensive drugs.

The BRACE CORONA trial was sponsored by D’Or Institute for Research and Education and the Brazilian Clinical Research Institute. Dr. Lopes has disclosed no relevant financial relationships.

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

Uterine papillary serous carcinoma (UPSC) is an infrequent but deadly form of endometrial cancer comprising 10% of cases but contributing 40% of deaths from the disease. Recurrence rates are high for this disease. Five-year survival is 55% for all patients and only 70% for stage I disease.¹ Patterns of recurrence tend to be distant (extrapelvic and extraabdominal) as frequently as they are localized to the pelvis, and metastases and recurrences are unrelated to the extent of uterine disease (such as myometrial invasion). It is for these reasons that the recommended course of adjuvant therapy for this disease is systemic therapy (typically six doses of carboplatin and paclitaxel chemotherapy) with consideration for radiation to the vagina or pelvis to consolidate pelvic and vaginal control.² This differs from early-stage high/intermediate–risk endometrioid adenocarcinomas, for which adjuvant chemotherapy has not been found to be helpful.

Dr Joshua Kish

Because of the lower incidence of UPSC, it frequently has been studied alongside endometrioid cell types in clinical trials which explore novel adjuvant therapies. However, UPSC is biologically distinct from endometrioid endometrial cancers, which likely results in inferior clinical responses to conventional interventions. Fortunately we are beginning to better understand UPSC at a molecular level, and advancements are being made in the targeted therapies for these patients that are unique, compared with those applied to other cancer subtypes.

As discussed above, UPSC is a particularly aggressive form of uterine cancer. Histologically it is characterized by a precursor lesion of endometrial glandular dysplasia progressing to endometrial intraepithelial neoplasia (EIC). Histologically it presents with a highly atypical slit-like glandular configuration, which appears similar to serous carcinomas of the fallopian tube and ovary. Molecularly these tumors commonly manifest mutations in tumor protein p53 (TP53) and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA), which are both genes associated with oncogenic potential.¹ While most UPSC tumors have loss of expression in hormone receptors such as estrogen and progesterone, 25%-30% of cases overexpress the tyrosine kinase receptor human epidermal growth factor receptor 2 (HER2).^3-5 This has proven to provide an exciting target for therapeutic interventions.
 

A target for therapeutic intervention

HER2 is a transmembrane receptor which, when activated, signals complex downstream pathways responsible for cellular proliferation, dedifferentiation, and metastasis. In a recent multi-institutional analysis of early-stage UPSC, HER2 overexpression was identified among 25% of cases.⁴ Approximately 30% of cases of advanced disease manifest overexpression of this biomarker.⁵ HER2 overexpression (HER2-positive status) is significantly associated with higher rates of recurrence and mortality, even among patients treated with conventional therapies.³ Thus HER2-positive status is obviously an indicator of particularly aggressive disease.

Fortunately this particular biomarker is one for which we have established and developing therapeutics. The humanized monoclonal antibody, trastuzumab, has been highly effective in improving survival for HER2-positive breast cancer.⁶ More recently, it was studied in a phase 2 trial with carboplatin and paclitaxel chemotherapy for advanced or recurrent HER2-positive UPSC.⁵ This trial showed that the addition of this targeted therapy to conventional chemotherapy improved recurrence-free survival from 8 months to 12 months, and improved overall survival from 24.4 months to 29.6 months.⁵
 

^{One discovery leads to another treatment}

This discovery led to the approval of trastuzumab to be used in addition to chemotherapy for advanced or recurrent disease.² The most significant effects appear to be among those who have not received prior therapies, with a doubling of progression-free survival among these patients, and a more modest response among patients treated for recurrent, mostly pretreated disease.

Work currently is underway to explore an array of antibody or small-molecule blockades of HER2 in addition to vaccines against the protein or treatment with conjugate compounds in which an antibody to HER2 is paired with a cytotoxic drug able to be internalized into HER2-expressing cells.⁷ This represents a form of personalized medicine referred to as biomarker-driven targeted therapy, in which therapies are prescribed based on the expression of specific molecular markers (such as HER2 expression) typically in combination with other clinical markers such as surgical staging results, race, age, etc. These approaches can be very effective strategies in rare tumor subtypes with distinct molecular and clinical behaviors.

As previously mentioned, the targeting of HER2 overexpression with trastuzumab has been shown to be highly effective in the treatment of HER2-positive breast cancers where even patients with early-stage disease receive a multimodal therapy approach including antibody, chemotherapy, surgical, and often radiation treatments.⁶ We are moving towards a similar multimodal comprehensive treatment strategy for UPSC. If it is as successful as it is in breast cancer, it will be long overdue, and desperately necessary given the poor prognosis of this disease for all stages because of the inadequacies of current treatments strategies.

Routine testing of UPSC for HER2 expression is now a part of routine molecular substaging of uterine cancers in the same way we have embraced testing for microsatellite instability and hormone-receptor status. While a diagnosis of HER2 overexpression in UPSC portends a poor prognosis, patients can be reassured that treatment strategies exist that can target this malignant mechanism in advanced disease and more are under further development for early-stage disease.
 

Dr. Rossi is assistant professor in the division of gynecologic oncology at the University of North Carolina at Chapel Hill. She has no relevant financial disclosures. Email her at obnews@mdedge.com.

References

1. Curr Opin Obstet Gynecol. 2010 Feb. doi: 10.1097/GCO.0b013e328334d8a3.

2. National Comprehensive Cancer Network. Uterine Neoplasms (version 2.2020).

3. Cancer 2005 Oct 1. doi: 10.1002/cncr.21308.

4. Gynecol Oncol 2020 doi: 10.1016/j.ygyno.2020.07.016.

5. J Clin Oncol 2018. doi: 10.1200/JCO.2017.76.5966.

6. N Engl J Med 2011. doi: 10.1056/NEJMoa0910383.

7. Discov Med. 2016 Apr;21(116):293-303.

Uterine papillary serous carcinoma (UPSC) is an infrequent but deadly form of endometrial cancer comprising 10% of cases but contributing 40% of deaths from the disease. Recurrence rates are high for this disease. Five-year survival is 55% for all patients and only 70% for stage I disease.¹ Patterns of recurrence tend to be distant (extrapelvic and extraabdominal) as frequently as they are localized to the pelvis, and metastases and recurrences are unrelated to the extent of uterine disease (such as myometrial invasion). It is for these reasons that the recommended course of adjuvant therapy for this disease is systemic therapy (typically six doses of carboplatin and paclitaxel chemotherapy) with consideration for radiation to the vagina or pelvis to consolidate pelvic and vaginal control.² This differs from early-stage high/intermediate–risk endometrioid adenocarcinomas, for which adjuvant chemotherapy has not been found to be helpful.

Dr Joshua Kish

Because of the lower incidence of UPSC, it frequently has been studied alongside endometrioid cell types in clinical trials which explore novel adjuvant therapies. However, UPSC is biologically distinct from endometrioid endometrial cancers, which likely results in inferior clinical responses to conventional interventions. Fortunately we are beginning to better understand UPSC at a molecular level, and advancements are being made in the targeted therapies for these patients that are unique, compared with those applied to other cancer subtypes.

As discussed above, UPSC is a particularly aggressive form of uterine cancer. Histologically it is characterized by a precursor lesion of endometrial glandular dysplasia progressing to endometrial intraepithelial neoplasia (EIC). Histologically it presents with a highly atypical slit-like glandular configuration, which appears similar to serous carcinomas of the fallopian tube and ovary. Molecularly these tumors commonly manifest mutations in tumor protein p53 (TP53) and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA), which are both genes associated with oncogenic potential.¹ While most UPSC tumors have loss of expression in hormone receptors such as estrogen and progesterone, 25%-30% of cases overexpress the tyrosine kinase receptor human epidermal growth factor receptor 2 (HER2).^3-5 This has proven to provide an exciting target for therapeutic interventions.
 

A target for therapeutic intervention

HER2 is a transmembrane receptor which, when activated, signals complex downstream pathways responsible for cellular proliferation, dedifferentiation, and metastasis. In a recent multi-institutional analysis of early-stage UPSC, HER2 overexpression was identified among 25% of cases.⁴ Approximately 30% of cases of advanced disease manifest overexpression of this biomarker.⁵ HER2 overexpression (HER2-positive status) is significantly associated with higher rates of recurrence and mortality, even among patients treated with conventional therapies.³ Thus HER2-positive status is obviously an indicator of particularly aggressive disease.

Fortunately this particular biomarker is one for which we have established and developing therapeutics. The humanized monoclonal antibody, trastuzumab, has been highly effective in improving survival for HER2-positive breast cancer.⁶ More recently, it was studied in a phase 2 trial with carboplatin and paclitaxel chemotherapy for advanced or recurrent HER2-positive UPSC.⁵ This trial showed that the addition of this targeted therapy to conventional chemotherapy improved recurrence-free survival from 8 months to 12 months, and improved overall survival from 24.4 months to 29.6 months.⁵
 

^{One discovery leads to another treatment}

This discovery led to the approval of trastuzumab to be used in addition to chemotherapy for advanced or recurrent disease.² The most significant effects appear to be among those who have not received prior therapies, with a doubling of progression-free survival among these patients, and a more modest response among patients treated for recurrent, mostly pretreated disease.

Work currently is underway to explore an array of antibody or small-molecule blockades of HER2 in addition to vaccines against the protein or treatment with conjugate compounds in which an antibody to HER2 is paired with a cytotoxic drug able to be internalized into HER2-expressing cells.⁷ This represents a form of personalized medicine referred to as biomarker-driven targeted therapy, in which therapies are prescribed based on the expression of specific molecular markers (such as HER2 expression) typically in combination with other clinical markers such as surgical staging results, race, age, etc. These approaches can be very effective strategies in rare tumor subtypes with distinct molecular and clinical behaviors.

As previously mentioned, the targeting of HER2 overexpression with trastuzumab has been shown to be highly effective in the treatment of HER2-positive breast cancers where even patients with early-stage disease receive a multimodal therapy approach including antibody, chemotherapy, surgical, and often radiation treatments.⁶ We are moving towards a similar multimodal comprehensive treatment strategy for UPSC. If it is as successful as it is in breast cancer, it will be long overdue, and desperately necessary given the poor prognosis of this disease for all stages because of the inadequacies of current treatments strategies.

Routine testing of UPSC for HER2 expression is now a part of routine molecular substaging of uterine cancers in the same way we have embraced testing for microsatellite instability and hormone-receptor status. While a diagnosis of HER2 overexpression in UPSC portends a poor prognosis, patients can be reassured that treatment strategies exist that can target this malignant mechanism in advanced disease and more are under further development for early-stage disease.
 

Dr. Rossi is assistant professor in the division of gynecologic oncology at the University of North Carolina at Chapel Hill. She has no relevant financial disclosures. Email her at obnews@mdedge.com.

References

1. Curr Opin Obstet Gynecol. 2010 Feb. doi: 10.1097/GCO.0b013e328334d8a3.

2. National Comprehensive Cancer Network. Uterine Neoplasms (version 2.2020).

3. Cancer 2005 Oct 1. doi: 10.1002/cncr.21308.

4. Gynecol Oncol 2020 doi: 10.1016/j.ygyno.2020.07.016.

5. J Clin Oncol 2018. doi: 10.1200/JCO.2017.76.5966.

6. N Engl J Med 2011. doi: 10.1056/NEJMoa0910383.

7. Discov Med. 2016 Apr;21(116):293-303.

Uterine papillary serous carcinoma (UPSC) is an infrequent but deadly form of endometrial cancer comprising 10% of cases but contributing 40% of deaths from the disease. Recurrence rates are high for this disease. Five-year survival is 55% for all patients and only 70% for stage I disease.¹ Patterns of recurrence tend to be distant (extrapelvic and extraabdominal) as frequently as they are localized to the pelvis, and metastases and recurrences are unrelated to the extent of uterine disease (such as myometrial invasion). It is for these reasons that the recommended course of adjuvant therapy for this disease is systemic therapy (typically six doses of carboplatin and paclitaxel chemotherapy) with consideration for radiation to the vagina or pelvis to consolidate pelvic and vaginal control.² This differs from early-stage high/intermediate–risk endometrioid adenocarcinomas, for which adjuvant chemotherapy has not been found to be helpful.

Dr Joshua Kish

Because of the lower incidence of UPSC, it frequently has been studied alongside endometrioid cell types in clinical trials which explore novel adjuvant therapies. However, UPSC is biologically distinct from endometrioid endometrial cancers, which likely results in inferior clinical responses to conventional interventions. Fortunately we are beginning to better understand UPSC at a molecular level, and advancements are being made in the targeted therapies for these patients that are unique, compared with those applied to other cancer subtypes.

As discussed above, UPSC is a particularly aggressive form of uterine cancer. Histologically it is characterized by a precursor lesion of endometrial glandular dysplasia progressing to endometrial intraepithelial neoplasia (EIC). Histologically it presents with a highly atypical slit-like glandular configuration, which appears similar to serous carcinomas of the fallopian tube and ovary. Molecularly these tumors commonly manifest mutations in tumor protein p53 (TP53) and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA), which are both genes associated with oncogenic potential.¹ While most UPSC tumors have loss of expression in hormone receptors such as estrogen and progesterone, 25%-30% of cases overexpress the tyrosine kinase receptor human epidermal growth factor receptor 2 (HER2).^3-5 This has proven to provide an exciting target for therapeutic interventions.
 

A target for therapeutic intervention

HER2 is a transmembrane receptor which, when activated, signals complex downstream pathways responsible for cellular proliferation, dedifferentiation, and metastasis. In a recent multi-institutional analysis of early-stage UPSC, HER2 overexpression was identified among 25% of cases.⁴ Approximately 30% of cases of advanced disease manifest overexpression of this biomarker.⁵ HER2 overexpression (HER2-positive status) is significantly associated with higher rates of recurrence and mortality, even among patients treated with conventional therapies.³ Thus HER2-positive status is obviously an indicator of particularly aggressive disease.

Fortunately this particular biomarker is one for which we have established and developing therapeutics. The humanized monoclonal antibody, trastuzumab, has been highly effective in improving survival for HER2-positive breast cancer.⁶ More recently, it was studied in a phase 2 trial with carboplatin and paclitaxel chemotherapy for advanced or recurrent HER2-positive UPSC.⁵ This trial showed that the addition of this targeted therapy to conventional chemotherapy improved recurrence-free survival from 8 months to 12 months, and improved overall survival from 24.4 months to 29.6 months.⁵
 

^{One discovery leads to another treatment}

This discovery led to the approval of trastuzumab to be used in addition to chemotherapy for advanced or recurrent disease.² The most significant effects appear to be among those who have not received prior therapies, with a doubling of progression-free survival among these patients, and a more modest response among patients treated for recurrent, mostly pretreated disease.

Work currently is underway to explore an array of antibody or small-molecule blockades of HER2 in addition to vaccines against the protein or treatment with conjugate compounds in which an antibody to HER2 is paired with a cytotoxic drug able to be internalized into HER2-expressing cells.⁷ This represents a form of personalized medicine referred to as biomarker-driven targeted therapy, in which therapies are prescribed based on the expression of specific molecular markers (such as HER2 expression) typically in combination with other clinical markers such as surgical staging results, race, age, etc. These approaches can be very effective strategies in rare tumor subtypes with distinct molecular and clinical behaviors.

As previously mentioned, the targeting of HER2 overexpression with trastuzumab has been shown to be highly effective in the treatment of HER2-positive breast cancers where even patients with early-stage disease receive a multimodal therapy approach including antibody, chemotherapy, surgical, and often radiation treatments.⁶ We are moving towards a similar multimodal comprehensive treatment strategy for UPSC. If it is as successful as it is in breast cancer, it will be long overdue, and desperately necessary given the poor prognosis of this disease for all stages because of the inadequacies of current treatments strategies.

Routine testing of UPSC for HER2 expression is now a part of routine molecular substaging of uterine cancers in the same way we have embraced testing for microsatellite instability and hormone-receptor status. While a diagnosis of HER2 overexpression in UPSC portends a poor prognosis, patients can be reassured that treatment strategies exist that can target this malignant mechanism in advanced disease and more are under further development for early-stage disease.
 

Dr. Rossi is assistant professor in the division of gynecologic oncology at the University of North Carolina at Chapel Hill. She has no relevant financial disclosures. Email her at obnews@mdedge.com.

References

1. Curr Opin Obstet Gynecol. 2010 Feb. doi: 10.1097/GCO.0b013e328334d8a3.

2. National Comprehensive Cancer Network. Uterine Neoplasms (version 2.2020).

3. Cancer 2005 Oct 1. doi: 10.1002/cncr.21308.

4. Gynecol Oncol 2020 doi: 10.1016/j.ygyno.2020.07.016.

5. J Clin Oncol 2018. doi: 10.1200/JCO.2017.76.5966.

6. N Engl J Med 2011. doi: 10.1056/NEJMoa0910383.

7. Discov Med. 2016 Apr;21(116):293-303.

During a telemedicine visit with his physician, a 62-year-old obese patient with an ankle injury reported new swelling of his leg. Three weeks had passed since the man visited an emergency department, where he underwent surgery and had a cast applied to the wound. The physician, during the telemedicine visit, advised the patient to elevate his leg and see an orthopedist within 24 hours. A Doppler ultrasound was ordered for 12:30 p.m. that same day.

The patient never made it to the appointment. He became unresponsive and went into full arrest hours later. His death fueled a lawsuit by his family that claimed failure to diagnose and treat deep venous thrombosis. The family contended the providers involved should have referred the patient to care immediately during the video visit.  

The case, which comes from the claims database of national medical liability insurer The Doctors Company, illustrates the legal risks that can stem from video visits with patients, says Richard Cahill, JD, vice president and associate general counsel for The Doctors Company.

“By evaluating the patient remotely, the physician failed to appreciate the often subtle nuances of the clinical presentation, which undoubtedly could have been more accurately assessed in the office setting, and would probably have led to more urgent evaluation and intervention, thereby likely preventing the unfortunate and otherwise avoidable result,” said Mr. Cahill.

According to a Harris poll, 42% of Americans reported using video visits during the pandemic, a trend that is likely to continue as practices reopen and virtual care becomes the norm. But as physicians conduct more video visits, so grows their risk for lawsuits associated with the technology. 

“We probably will see more malpractice suits filed the more telehealth is used,” said Mei Wa Kwong, JD, executive director of the Center for Connected Health Policy. “It’s a numbers game. The more it’s used, the higher likelihood that lawsuits occur.”
 

Three problems in not being able to touch the patient

1. The primary challenge with video visits “is the inability to directly observe and lay hands on the patient,” says Jonathan Einbinder, MD, assistant vice president of analytics for CRICO, a medical liability insurer based in Boston.

“While you can see them via video, it can be hard to get a full sense of how sick the patient is and whether other things might be going on than what they are reporting,” said Dr. Einbinder, a practicing internist. 

Such incomplete pictures can lead to diagnostic errors and the potential for lawsuits, as demonstrated by a recent CRICO analysis. Of 106 telemedicine-related claims from 2014 to 2018, 66% were diagnosis related, according to the analysis of claims from CRICO’s national database. Twelve percent of the telemedicine-related claims were associated with surgical treatment, 11% were related to medical treatment, and 5% were associated with medication issues. A smaller number of claims resulted from patient monitoring, ob.gyn. care, and safety and security.

Another analysis by The Doctors Company similarly determined that diagnostic errors are the most common allegation in telemedicine-related claims. In the study of 28 telemedicine-related claims from The Doctors’ database, 71% were diagnosis related, 11% were associated with mismanagement of treatment, and 7% were related to improper management of a surgical patient. Other allegations included improper performance of treatment or procedure and improper performance of surgery.

“Because a ‘typical’ exam can’t be done, there is the potential to miss things,” said David L. Feldman, MD, chief medical officer for The Doctors Company Group. “A subtlety, perhaps a lump that can’t be seen but only felt, and only by an experienced examiner, for example, may be missed.” 

2. Documentation dangers also loom, said William Sullivan, DO, JD, an emergency physician and an attorney who specializes in health care. The legal risk lies in documenting a video visit in the same way the doctor would document an in-person visit, he explained.

“Investigation into a potential lawsuit begins when there is some type of bad outcome related to medical care,” Dr. Sullivan explained. “To determine whether the lawsuit has merit, patients/attorneys review the medical records to retrospectively determine the potential cause of the bad outcome. If the documentation reflects an examination that could not have been performed, a lawyer might be more likely to pursue a case, and it would be more difficult to defend the care provided.”

Dr. Sullivan provided this example: During a video visit, a patient complains of acute onset weakness. The physician documents that the patient’s heart has a “regular rate and rhythm,” and “muscle strength is equal bilaterally.” The following day, the patient’s weakness continues, and the patient goes to the emergency department where he is diagnosed with stroke. An EKG in the ED shows that the patient is in atrial fibrillation.

“The telehealth provider would have a difficult time explaining how it was determined that the patient had normal muscle strength and a normal heart rhythm over a video visit the day before,” Dr. Sullivan said. “A lawyer in a subsequent malpractice case would present the provider as careless and would argue that if the provider had only sent the patient to the emergency department after the telehealth visit instead of documenting exam findings that couldn’t have been performed, the patient could have been successfully treated for the stroke.”

3. Poorly executed informed consent can also give rise to a lawsuit. This includes informed consent regarding the use of telehealth as the accepted modality for the visit rather than traditional on-site evaluations, as well as preprocedure informed consent.

“Inadequate and/or poorly documented informed consent can result in a claim for medical battery,” Mr. Cahill said.

A medical battery allegation refers to the alleged treatment or touching of a patient’s body without that person’s consent. As the AMA Journal of Ethics explains, a patient’s consent must be given, either expressly or implicitly, before a physician may legally “interfere” with the physical body of the patient.

Ideally, the informed consent process is undertaken during a first in-person visit, before virtual visits begin, Dr. Feldman said.

“There is a lot that a patient has to understand when a visit is done virtually, which is part of the informed consent process,” Dr. Feldman said. “The pandemic has forced some physicians to do their first visit virtually, and this makes the process of informing patients more onerous. It is not a simple matter of converting an in-person office practice to a remote office practice. The work flows are different, so there are definitely legal concerns as it relates to privacy and cybersecurity to name a few.”
 

Waivers may be weak protection

Since the pandemic started, a number of states have enacted emergency malpractice protections to shield health professionals from lawsuits. Some protections, such as those in Massachusetts, offer immunity to health professionals who provide general care to patients during the COVID-19 emergency, in addition to treatment of COVID-19 patients. Other protections, like those in Connecticut, apply specifically to care provided in support of the state’s pandemic response.

Whether that immunity applies both to in-person visits and video visits during the pandemic is not certain, said J. Richard Moore, JD, a medical liability defense attorney based in Indianapolis. Indiana’s immunity statute for example, does not make a specific provision for telehealth, he said.

“My best prediction is that if considered by the courts, the immunity would be applied to telehealth services, so long as they are being provided ‘in response to the emergency,’ which is the scope of the immunity,” he said. “I would not consider telehealth physicians to be either more or less protected than in-person providers.”

Regulatory scrutiny for telehealth providers has also been relaxed in response to COVID-19, but experts warn not to rely on the temporary shields for ultimate protection.

In March, the U.S. Department of Health and Human Service’s Office of Civil Rights (OCR) eased enforcement actions for noncompliance with Health Insurance Portability and Accountability Act requirements in connection with the good faith provision of telehealth during the COVID-19 health crisis. Under the notice, health providers can use popular applications such as Apple FaceTime, Facebook Messenger, Zoom, or Google Hangouts, to offer telehealth care without risk that OCR will impose fines or penalties for HIPAA violations.

But once the current health care emergency is mitigated, the waivers will likely be withdrawn, and enforcement actions will probably resume, Mr. Cahill said.

“It is recommended that, to avoid potential problems going forward, practitioners use due diligence and undertake best efforts to obey existing privacy and security requirements, including the use of technology that satisfies compliance regulations, despite the waiver by OCR,” he said.

In addition, a majority of states have relaxed state-specific rules for practicing telehealth and loosened licensure requirements during the pandemic. At least 47 states have issued waivers to alter in-state licensure requirements for telemedicine in response to COVID-19, according to the Federation of State Medical Boards. Most of the waivers allow physicians licensed in other states to provide care in states where they do not hold licenses, and some enable doctors to treat patients without first having had an in-person evaluation.

But at least for now, these are temporary changes, reminds Amy Lerman, JD, a health care attorney based in Washington, who specializes in telehealth and corporate compliance. Given the current pandemic environment, a significant concern is that physicians new to the telemedicine space are reacting only to the most recent rules established in the context of the pandemic, Ms. Lerman said.

“As previously noted, the recent developments are temporary in nature – states and various federal agencies have been pretty clear in setting this temporal boundary,” she said. “It is not advisable for providers to build telepractice models around temporary sets of rules. 

“Furthermore, the recent developments are not necessarily comprehensive relative to all of the state-specific and other requirements that telemedicine providers are otherwise expected to follow, so relying only on the most recent guidance may cause providers to create telepractice models that have key gaps with respect to regulatory compliance.”
 

How you can avoid a lawsuit

As businesses reopen and practices resume treatments, physicians should weigh the choice between in-person care and video visits very carefully, said Joseph Kvedar, MD, president of the American Telemedicine Association and a dermatology professor at Harvard Medical School, Boston.

“We have to be very thoughtful about quality in this current phase, where we are doing what I call a hybrid model,” he said. “Some services are offered by telehealth and some require patients to come into the doctor’s office. We have to be very thoughtful about what types of care we determine to be appropriate for telehealth, and that has to be based on clinical quality. And if it is, it should follow that we’ll have low incidence of liability claims.”

Data should be at the center of that conclusion, Dr. Kvedar advises.

“Think about what data is needed to make a therapeutic or diagnostic decision,” he said. “If a health care provider can gather the information needed without touching the patient, then the provider is probably on safe, solid ground making that decision via a telehealth interaction. If the patient can come into the doctor’s office, and the provider deems it necessary to see the patient in person and touch the patient in order to make that clinical decision, then the patient should come in.”

An important step to preventing liability is also having strong telehealth systems and protocols in place and the necessary support to carry them out, said Dr. Einbinder of medical liability insurer CRICO.

For example, Dr. Einbinder, who practices in a 12-doctor internal medicine group, said when he finishes a virtual visit, he enters any orders into the electronic health record. Some of the orders will result in notifications to Dr. Einbinder if they are not executed, such as a referral appointment or a procedure that was not completed. 

“I also can forward my orders to a front desk pool that is responsible for making sure things get done,” he said. “And, in our hospital system, we have good case management for complex patients and population management for a variety of chronic conditions. These represent additional safety nets.” 

Another liability safeguard is sending patients a “visit summary” after each virtual visit, Dr. Sullivan said. This could be in the form of an email or a text that includes a brief template including items such as diagnosis, recommendations, follow-up, and a reminder to contact the doctor or go to the emergency department if symptoms worsen or new problems develop.

“Patients tend to remember about half of what physicians tell them and half of the information patients do remember is incorrect,” he said. “Consider a few sentences in an e-mail or text message as a substitute for the after-visit instructions from an office visit to enhance patient understanding. There are several inexpensive programs/services that allow text messages to be sent from a computer using a separate dedicated phone number and pretty much every patient has a cell phone to receive the instructions.”

Dr. Sullivan suggests having a documentation template specifically for telehealth visits. He also recommends the inclusion an “informed refusal of care” in the record when necessary. Dr. Sullivan’s wife, a family physician, has encountered several patients who fear contracting COVID-19 and who have refused her recommendations for in-person visits, he said. In such cases, he said it’s a good idea to document that the patient decided to forgo the recommendations given.

“If a patient suffers a bad outcome because of a failure to seek an in-person exam, a short note in the patient’s chart would help to establish that the lack of a follow-up physical exam was the patient’s informed decision, not due to some alleged negligence of the medical provider,” he said.

Concerning informed consent, Dr. Feldman says at a minimum physicians should discuss the following with patients:

• Names and credentials of staff participating.
• The right to stop or refuse treatment by telemedicine.
• Technology that will be used.
• Privacy and security risks.
• Technology-specific risks and permission to bill.
• Alternative care in case of an emergency or technology malfunction.
• Any state-specific requirements.

“Physicians can ensure they have a strong informed consent process during video visits by taking the time to cover these points at the beginning of the first visit, and being sure the patient understands and agrees to these,” Dr. Sullivan explained. “Ideally, this conversation can be recorded for future reference if necessary or at a minimum documented in the medical record.”
 

Consider these extra precautions

Mr. Cahill advises that practitioners be especially mindful of their “web-side manner” and the setting in which they are communicating with virtual patients to promote confidentiality, professionalism, and uninterrupted interactions.

“Use of a headset in a quiet home office is advisable,” he said. “Physicians must also be cognizant of their physical appearance and the background behind them when the visit includes both audio and visual capability. For ‘face-to-face’ telehealth encounters, it is recommended that a white lab jacket be worn as the appropriate attire; coat and tie are unnecessary.”

Some patients may need to be reminded of the need for confidentiality during a video visit, Mr. Moore added. Physicians are typically in a position to ensure confidentiality, but some patients may not understand how to protect their privacy on their end. 

“If the physician sees on the screen or hears from an audio connection that there are other people around who may be able to overhear what is communicated, the physician probably has some responsibility to remind the patient that she or he may want to go to a more private place, close the door, etc.,” he said. “While I think a claim against a physician on this basis would be pretty weak, it is still a good practice for the physician to be cognizant of those kinds of concerns even if the patient is not.”

Finally, for physicians who set up telehealth operability during the pandemic – possibly in a hurry – consider using your actual case data to take a look backward, said Ms. Lerman, the Washington-based health care attorney. Reviewing the data can help determine whether you’re in compliance with relevant state laws, she said. 

“If, for example, a provider set up telehealth operations during the pandemic and can see that most of [the] patients are based in a single state, or a small group of states, it is worthwhile to take [the] time and become familiar with the telemedicine laws in those states,” she said. “If there are modifications that need to be made, it may be easier to make them incrementally before the telehealth operations grow any larger in scope.” 

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

During a telemedicine visit with his physician, a 62-year-old obese patient with an ankle injury reported new swelling of his leg. Three weeks had passed since the man visited an emergency department, where he underwent surgery and had a cast applied to the wound. The physician, during the telemedicine visit, advised the patient to elevate his leg and see an orthopedist within 24 hours. A Doppler ultrasound was ordered for 12:30 p.m. that same day.

The patient never made it to the appointment. He became unresponsive and went into full arrest hours later. His death fueled a lawsuit by his family that claimed failure to diagnose and treat deep venous thrombosis. The family contended the providers involved should have referred the patient to care immediately during the video visit.  

The case, which comes from the claims database of national medical liability insurer The Doctors Company, illustrates the legal risks that can stem from video visits with patients, says Richard Cahill, JD, vice president and associate general counsel for The Doctors Company.

“By evaluating the patient remotely, the physician failed to appreciate the often subtle nuances of the clinical presentation, which undoubtedly could have been more accurately assessed in the office setting, and would probably have led to more urgent evaluation and intervention, thereby likely preventing the unfortunate and otherwise avoidable result,” said Mr. Cahill.

According to a Harris poll, 42% of Americans reported using video visits during the pandemic, a trend that is likely to continue as practices reopen and virtual care becomes the norm. But as physicians conduct more video visits, so grows their risk for lawsuits associated with the technology. 

“We probably will see more malpractice suits filed the more telehealth is used,” said Mei Wa Kwong, JD, executive director of the Center for Connected Health Policy. “It’s a numbers game. The more it’s used, the higher likelihood that lawsuits occur.”
 

Three problems in not being able to touch the patient

1. The primary challenge with video visits “is the inability to directly observe and lay hands on the patient,” says Jonathan Einbinder, MD, assistant vice president of analytics for CRICO, a medical liability insurer based in Boston.

“While you can see them via video, it can be hard to get a full sense of how sick the patient is and whether other things might be going on than what they are reporting,” said Dr. Einbinder, a practicing internist. 

Such incomplete pictures can lead to diagnostic errors and the potential for lawsuits, as demonstrated by a recent CRICO analysis. Of 106 telemedicine-related claims from 2014 to 2018, 66% were diagnosis related, according to the analysis of claims from CRICO’s national database. Twelve percent of the telemedicine-related claims were associated with surgical treatment, 11% were related to medical treatment, and 5% were associated with medication issues. A smaller number of claims resulted from patient monitoring, ob.gyn. care, and safety and security.

Another analysis by The Doctors Company similarly determined that diagnostic errors are the most common allegation in telemedicine-related claims. In the study of 28 telemedicine-related claims from The Doctors’ database, 71% were diagnosis related, 11% were associated with mismanagement of treatment, and 7% were related to improper management of a surgical patient. Other allegations included improper performance of treatment or procedure and improper performance of surgery.

“Because a ‘typical’ exam can’t be done, there is the potential to miss things,” said David L. Feldman, MD, chief medical officer for The Doctors Company Group. “A subtlety, perhaps a lump that can’t be seen but only felt, and only by an experienced examiner, for example, may be missed.” 

2. Documentation dangers also loom, said William Sullivan, DO, JD, an emergency physician and an attorney who specializes in health care. The legal risk lies in documenting a video visit in the same way the doctor would document an in-person visit, he explained.

“Investigation into a potential lawsuit begins when there is some type of bad outcome related to medical care,” Dr. Sullivan explained. “To determine whether the lawsuit has merit, patients/attorneys review the medical records to retrospectively determine the potential cause of the bad outcome. If the documentation reflects an examination that could not have been performed, a lawyer might be more likely to pursue a case, and it would be more difficult to defend the care provided.”

Dr. Sullivan provided this example: During a video visit, a patient complains of acute onset weakness. The physician documents that the patient’s heart has a “regular rate and rhythm,” and “muscle strength is equal bilaterally.” The following day, the patient’s weakness continues, and the patient goes to the emergency department where he is diagnosed with stroke. An EKG in the ED shows that the patient is in atrial fibrillation.

“The telehealth provider would have a difficult time explaining how it was determined that the patient had normal muscle strength and a normal heart rhythm over a video visit the day before,” Dr. Sullivan said. “A lawyer in a subsequent malpractice case would present the provider as careless and would argue that if the provider had only sent the patient to the emergency department after the telehealth visit instead of documenting exam findings that couldn’t have been performed, the patient could have been successfully treated for the stroke.”

3. Poorly executed informed consent can also give rise to a lawsuit. This includes informed consent regarding the use of telehealth as the accepted modality for the visit rather than traditional on-site evaluations, as well as preprocedure informed consent.

“Inadequate and/or poorly documented informed consent can result in a claim for medical battery,” Mr. Cahill said.

A medical battery allegation refers to the alleged treatment or touching of a patient’s body without that person’s consent. As the AMA Journal of Ethics explains, a patient’s consent must be given, either expressly or implicitly, before a physician may legally “interfere” with the physical body of the patient.

Ideally, the informed consent process is undertaken during a first in-person visit, before virtual visits begin, Dr. Feldman said.

“There is a lot that a patient has to understand when a visit is done virtually, which is part of the informed consent process,” Dr. Feldman said. “The pandemic has forced some physicians to do their first visit virtually, and this makes the process of informing patients more onerous. It is not a simple matter of converting an in-person office practice to a remote office practice. The work flows are different, so there are definitely legal concerns as it relates to privacy and cybersecurity to name a few.”
 

Waivers may be weak protection

Since the pandemic started, a number of states have enacted emergency malpractice protections to shield health professionals from lawsuits. Some protections, such as those in Massachusetts, offer immunity to health professionals who provide general care to patients during the COVID-19 emergency, in addition to treatment of COVID-19 patients. Other protections, like those in Connecticut, apply specifically to care provided in support of the state’s pandemic response.

Whether that immunity applies both to in-person visits and video visits during the pandemic is not certain, said J. Richard Moore, JD, a medical liability defense attorney based in Indianapolis. Indiana’s immunity statute for example, does not make a specific provision for telehealth, he said.

“My best prediction is that if considered by the courts, the immunity would be applied to telehealth services, so long as they are being provided ‘in response to the emergency,’ which is the scope of the immunity,” he said. “I would not consider telehealth physicians to be either more or less protected than in-person providers.”

Regulatory scrutiny for telehealth providers has also been relaxed in response to COVID-19, but experts warn not to rely on the temporary shields for ultimate protection.

In March, the U.S. Department of Health and Human Service’s Office of Civil Rights (OCR) eased enforcement actions for noncompliance with Health Insurance Portability and Accountability Act requirements in connection with the good faith provision of telehealth during the COVID-19 health crisis. Under the notice, health providers can use popular applications such as Apple FaceTime, Facebook Messenger, Zoom, or Google Hangouts, to offer telehealth care without risk that OCR will impose fines or penalties for HIPAA violations.

But once the current health care emergency is mitigated, the waivers will likely be withdrawn, and enforcement actions will probably resume, Mr. Cahill said.

“It is recommended that, to avoid potential problems going forward, practitioners use due diligence and undertake best efforts to obey existing privacy and security requirements, including the use of technology that satisfies compliance regulations, despite the waiver by OCR,” he said.

In addition, a majority of states have relaxed state-specific rules for practicing telehealth and loosened licensure requirements during the pandemic. At least 47 states have issued waivers to alter in-state licensure requirements for telemedicine in response to COVID-19, according to the Federation of State Medical Boards. Most of the waivers allow physicians licensed in other states to provide care in states where they do not hold licenses, and some enable doctors to treat patients without first having had an in-person evaluation.

But at least for now, these are temporary changes, reminds Amy Lerman, JD, a health care attorney based in Washington, who specializes in telehealth and corporate compliance. Given the current pandemic environment, a significant concern is that physicians new to the telemedicine space are reacting only to the most recent rules established in the context of the pandemic, Ms. Lerman said.

“As previously noted, the recent developments are temporary in nature – states and various federal agencies have been pretty clear in setting this temporal boundary,” she said. “It is not advisable for providers to build telepractice models around temporary sets of rules. 

“Furthermore, the recent developments are not necessarily comprehensive relative to all of the state-specific and other requirements that telemedicine providers are otherwise expected to follow, so relying only on the most recent guidance may cause providers to create telepractice models that have key gaps with respect to regulatory compliance.”
 

How you can avoid a lawsuit

As businesses reopen and practices resume treatments, physicians should weigh the choice between in-person care and video visits very carefully, said Joseph Kvedar, MD, president of the American Telemedicine Association and a dermatology professor at Harvard Medical School, Boston.

“We have to be very thoughtful about quality in this current phase, where we are doing what I call a hybrid model,” he said. “Some services are offered by telehealth and some require patients to come into the doctor’s office. We have to be very thoughtful about what types of care we determine to be appropriate for telehealth, and that has to be based on clinical quality. And if it is, it should follow that we’ll have low incidence of liability claims.”

Data should be at the center of that conclusion, Dr. Kvedar advises.

“Think about what data is needed to make a therapeutic or diagnostic decision,” he said. “If a health care provider can gather the information needed without touching the patient, then the provider is probably on safe, solid ground making that decision via a telehealth interaction. If the patient can come into the doctor’s office, and the provider deems it necessary to see the patient in person and touch the patient in order to make that clinical decision, then the patient should come in.”

An important step to preventing liability is also having strong telehealth systems and protocols in place and the necessary support to carry them out, said Dr. Einbinder of medical liability insurer CRICO.

For example, Dr. Einbinder, who practices in a 12-doctor internal medicine group, said when he finishes a virtual visit, he enters any orders into the electronic health record. Some of the orders will result in notifications to Dr. Einbinder if they are not executed, such as a referral appointment or a procedure that was not completed. 

“I also can forward my orders to a front desk pool that is responsible for making sure things get done,” he said. “And, in our hospital system, we have good case management for complex patients and population management for a variety of chronic conditions. These represent additional safety nets.” 

Another liability safeguard is sending patients a “visit summary” after each virtual visit, Dr. Sullivan said. This could be in the form of an email or a text that includes a brief template including items such as diagnosis, recommendations, follow-up, and a reminder to contact the doctor or go to the emergency department if symptoms worsen or new problems develop.

“Patients tend to remember about half of what physicians tell them and half of the information patients do remember is incorrect,” he said. “Consider a few sentences in an e-mail or text message as a substitute for the after-visit instructions from an office visit to enhance patient understanding. There are several inexpensive programs/services that allow text messages to be sent from a computer using a separate dedicated phone number and pretty much every patient has a cell phone to receive the instructions.”

Dr. Sullivan suggests having a documentation template specifically for telehealth visits. He also recommends the inclusion an “informed refusal of care” in the record when necessary. Dr. Sullivan’s wife, a family physician, has encountered several patients who fear contracting COVID-19 and who have refused her recommendations for in-person visits, he said. In such cases, he said it’s a good idea to document that the patient decided to forgo the recommendations given.

“If a patient suffers a bad outcome because of a failure to seek an in-person exam, a short note in the patient’s chart would help to establish that the lack of a follow-up physical exam was the patient’s informed decision, not due to some alleged negligence of the medical provider,” he said.

Concerning informed consent, Dr. Feldman says at a minimum physicians should discuss the following with patients:

• Names and credentials of staff participating.
• The right to stop or refuse treatment by telemedicine.
• Technology that will be used.
• Privacy and security risks.
• Technology-specific risks and permission to bill.
• Alternative care in case of an emergency or technology malfunction.
• Any state-specific requirements.

“Physicians can ensure they have a strong informed consent process during video visits by taking the time to cover these points at the beginning of the first visit, and being sure the patient understands and agrees to these,” Dr. Sullivan explained. “Ideally, this conversation can be recorded for future reference if necessary or at a minimum documented in the medical record.”
 

Consider these extra precautions

Mr. Cahill advises that practitioners be especially mindful of their “web-side manner” and the setting in which they are communicating with virtual patients to promote confidentiality, professionalism, and uninterrupted interactions.

“Use of a headset in a quiet home office is advisable,” he said. “Physicians must also be cognizant of their physical appearance and the background behind them when the visit includes both audio and visual capability. For ‘face-to-face’ telehealth encounters, it is recommended that a white lab jacket be worn as the appropriate attire; coat and tie are unnecessary.”

Some patients may need to be reminded of the need for confidentiality during a video visit, Mr. Moore added. Physicians are typically in a position to ensure confidentiality, but some patients may not understand how to protect their privacy on their end. 

“If the physician sees on the screen or hears from an audio connection that there are other people around who may be able to overhear what is communicated, the physician probably has some responsibility to remind the patient that she or he may want to go to a more private place, close the door, etc.,” he said. “While I think a claim against a physician on this basis would be pretty weak, it is still a good practice for the physician to be cognizant of those kinds of concerns even if the patient is not.”

Finally, for physicians who set up telehealth operability during the pandemic – possibly in a hurry – consider using your actual case data to take a look backward, said Ms. Lerman, the Washington-based health care attorney. Reviewing the data can help determine whether you’re in compliance with relevant state laws, she said. 

“If, for example, a provider set up telehealth operations during the pandemic and can see that most of [the] patients are based in a single state, or a small group of states, it is worthwhile to take [the] time and become familiar with the telemedicine laws in those states,” she said. “If there are modifications that need to be made, it may be easier to make them incrementally before the telehealth operations grow any larger in scope.” 

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

During a telemedicine visit with his physician, a 62-year-old obese patient with an ankle injury reported new swelling of his leg. Three weeks had passed since the man visited an emergency department, where he underwent surgery and had a cast applied to the wound. The physician, during the telemedicine visit, advised the patient to elevate his leg and see an orthopedist within 24 hours. A Doppler ultrasound was ordered for 12:30 p.m. that same day.

The patient never made it to the appointment. He became unresponsive and went into full arrest hours later. His death fueled a lawsuit by his family that claimed failure to diagnose and treat deep venous thrombosis. The family contended the providers involved should have referred the patient to care immediately during the video visit.  

The case, which comes from the claims database of national medical liability insurer The Doctors Company, illustrates the legal risks that can stem from video visits with patients, says Richard Cahill, JD, vice president and associate general counsel for The Doctors Company.

“By evaluating the patient remotely, the physician failed to appreciate the often subtle nuances of the clinical presentation, which undoubtedly could have been more accurately assessed in the office setting, and would probably have led to more urgent evaluation and intervention, thereby likely preventing the unfortunate and otherwise avoidable result,” said Mr. Cahill.

According to a Harris poll, 42% of Americans reported using video visits during the pandemic, a trend that is likely to continue as practices reopen and virtual care becomes the norm. But as physicians conduct more video visits, so grows their risk for lawsuits associated with the technology. 

“We probably will see more malpractice suits filed the more telehealth is used,” said Mei Wa Kwong, JD, executive director of the Center for Connected Health Policy. “It’s a numbers game. The more it’s used, the higher likelihood that lawsuits occur.”
 

Three problems in not being able to touch the patient

1. The primary challenge with video visits “is the inability to directly observe and lay hands on the patient,” says Jonathan Einbinder, MD, assistant vice president of analytics for CRICO, a medical liability insurer based in Boston.

“While you can see them via video, it can be hard to get a full sense of how sick the patient is and whether other things might be going on than what they are reporting,” said Dr. Einbinder, a practicing internist. 

Such incomplete pictures can lead to diagnostic errors and the potential for lawsuits, as demonstrated by a recent CRICO analysis. Of 106 telemedicine-related claims from 2014 to 2018, 66% were diagnosis related, according to the analysis of claims from CRICO’s national database. Twelve percent of the telemedicine-related claims were associated with surgical treatment, 11% were related to medical treatment, and 5% were associated with medication issues. A smaller number of claims resulted from patient monitoring, ob.gyn. care, and safety and security.

Another analysis by The Doctors Company similarly determined that diagnostic errors are the most common allegation in telemedicine-related claims. In the study of 28 telemedicine-related claims from The Doctors’ database, 71% were diagnosis related, 11% were associated with mismanagement of treatment, and 7% were related to improper management of a surgical patient. Other allegations included improper performance of treatment or procedure and improper performance of surgery.

“Because a ‘typical’ exam can’t be done, there is the potential to miss things,” said David L. Feldman, MD, chief medical officer for The Doctors Company Group. “A subtlety, perhaps a lump that can’t be seen but only felt, and only by an experienced examiner, for example, may be missed.” 

2. Documentation dangers also loom, said William Sullivan, DO, JD, an emergency physician and an attorney who specializes in health care. The legal risk lies in documenting a video visit in the same way the doctor would document an in-person visit, he explained.

“Investigation into a potential lawsuit begins when there is some type of bad outcome related to medical care,” Dr. Sullivan explained. “To determine whether the lawsuit has merit, patients/attorneys review the medical records to retrospectively determine the potential cause of the bad outcome. If the documentation reflects an examination that could not have been performed, a lawyer might be more likely to pursue a case, and it would be more difficult to defend the care provided.”

Dr. Sullivan provided this example: During a video visit, a patient complains of acute onset weakness. The physician documents that the patient’s heart has a “regular rate and rhythm,” and “muscle strength is equal bilaterally.” The following day, the patient’s weakness continues, and the patient goes to the emergency department where he is diagnosed with stroke. An EKG in the ED shows that the patient is in atrial fibrillation.

“The telehealth provider would have a difficult time explaining how it was determined that the patient had normal muscle strength and a normal heart rhythm over a video visit the day before,” Dr. Sullivan said. “A lawyer in a subsequent malpractice case would present the provider as careless and would argue that if the provider had only sent the patient to the emergency department after the telehealth visit instead of documenting exam findings that couldn’t have been performed, the patient could have been successfully treated for the stroke.”

3. Poorly executed informed consent can also give rise to a lawsuit. This includes informed consent regarding the use of telehealth as the accepted modality for the visit rather than traditional on-site evaluations, as well as preprocedure informed consent.

“Inadequate and/or poorly documented informed consent can result in a claim for medical battery,” Mr. Cahill said.

A medical battery allegation refers to the alleged treatment or touching of a patient’s body without that person’s consent. As the AMA Journal of Ethics explains, a patient’s consent must be given, either expressly or implicitly, before a physician may legally “interfere” with the physical body of the patient.

Ideally, the informed consent process is undertaken during a first in-person visit, before virtual visits begin, Dr. Feldman said.

“There is a lot that a patient has to understand when a visit is done virtually, which is part of the informed consent process,” Dr. Feldman said. “The pandemic has forced some physicians to do their first visit virtually, and this makes the process of informing patients more onerous. It is not a simple matter of converting an in-person office practice to a remote office practice. The work flows are different, so there are definitely legal concerns as it relates to privacy and cybersecurity to name a few.”
 

Waivers may be weak protection

Since the pandemic started, a number of states have enacted emergency malpractice protections to shield health professionals from lawsuits. Some protections, such as those in Massachusetts, offer immunity to health professionals who provide general care to patients during the COVID-19 emergency, in addition to treatment of COVID-19 patients. Other protections, like those in Connecticut, apply specifically to care provided in support of the state’s pandemic response.

Whether that immunity applies both to in-person visits and video visits during the pandemic is not certain, said J. Richard Moore, JD, a medical liability defense attorney based in Indianapolis. Indiana’s immunity statute for example, does not make a specific provision for telehealth, he said.

“My best prediction is that if considered by the courts, the immunity would be applied to telehealth services, so long as they are being provided ‘in response to the emergency,’ which is the scope of the immunity,” he said. “I would not consider telehealth physicians to be either more or less protected than in-person providers.”

Regulatory scrutiny for telehealth providers has also been relaxed in response to COVID-19, but experts warn not to rely on the temporary shields for ultimate protection.

In March, the U.S. Department of Health and Human Service’s Office of Civil Rights (OCR) eased enforcement actions for noncompliance with Health Insurance Portability and Accountability Act requirements in connection with the good faith provision of telehealth during the COVID-19 health crisis. Under the notice, health providers can use popular applications such as Apple FaceTime, Facebook Messenger, Zoom, or Google Hangouts, to offer telehealth care without risk that OCR will impose fines or penalties for HIPAA violations.

But once the current health care emergency is mitigated, the waivers will likely be withdrawn, and enforcement actions will probably resume, Mr. Cahill said.

“It is recommended that, to avoid potential problems going forward, practitioners use due diligence and undertake best efforts to obey existing privacy and security requirements, including the use of technology that satisfies compliance regulations, despite the waiver by OCR,” he said.

In addition, a majority of states have relaxed state-specific rules for practicing telehealth and loosened licensure requirements during the pandemic. At least 47 states have issued waivers to alter in-state licensure requirements for telemedicine in response to COVID-19, according to the Federation of State Medical Boards. Most of the waivers allow physicians licensed in other states to provide care in states where they do not hold licenses, and some enable doctors to treat patients without first having had an in-person evaluation.

But at least for now, these are temporary changes, reminds Amy Lerman, JD, a health care attorney based in Washington, who specializes in telehealth and corporate compliance. Given the current pandemic environment, a significant concern is that physicians new to the telemedicine space are reacting only to the most recent rules established in the context of the pandemic, Ms. Lerman said.

“As previously noted, the recent developments are temporary in nature – states and various federal agencies have been pretty clear in setting this temporal boundary,” she said. “It is not advisable for providers to build telepractice models around temporary sets of rules. 

“Furthermore, the recent developments are not necessarily comprehensive relative to all of the state-specific and other requirements that telemedicine providers are otherwise expected to follow, so relying only on the most recent guidance may cause providers to create telepractice models that have key gaps with respect to regulatory compliance.”
 

How you can avoid a lawsuit

As businesses reopen and practices resume treatments, physicians should weigh the choice between in-person care and video visits very carefully, said Joseph Kvedar, MD, president of the American Telemedicine Association and a dermatology professor at Harvard Medical School, Boston.

“We have to be very thoughtful about quality in this current phase, where we are doing what I call a hybrid model,” he said. “Some services are offered by telehealth and some require patients to come into the doctor’s office. We have to be very thoughtful about what types of care we determine to be appropriate for telehealth, and that has to be based on clinical quality. And if it is, it should follow that we’ll have low incidence of liability claims.”

Data should be at the center of that conclusion, Dr. Kvedar advises.

“Think about what data is needed to make a therapeutic or diagnostic decision,” he said. “If a health care provider can gather the information needed without touching the patient, then the provider is probably on safe, solid ground making that decision via a telehealth interaction. If the patient can come into the doctor’s office, and the provider deems it necessary to see the patient in person and touch the patient in order to make that clinical decision, then the patient should come in.”

An important step to preventing liability is also having strong telehealth systems and protocols in place and the necessary support to carry them out, said Dr. Einbinder of medical liability insurer CRICO.

For example, Dr. Einbinder, who practices in a 12-doctor internal medicine group, said when he finishes a virtual visit, he enters any orders into the electronic health record. Some of the orders will result in notifications to Dr. Einbinder if they are not executed, such as a referral appointment or a procedure that was not completed. 

“I also can forward my orders to a front desk pool that is responsible for making sure things get done,” he said. “And, in our hospital system, we have good case management for complex patients and population management for a variety of chronic conditions. These represent additional safety nets.” 

Another liability safeguard is sending patients a “visit summary” after each virtual visit, Dr. Sullivan said. This could be in the form of an email or a text that includes a brief template including items such as diagnosis, recommendations, follow-up, and a reminder to contact the doctor or go to the emergency department if symptoms worsen or new problems develop.

“Patients tend to remember about half of what physicians tell them and half of the information patients do remember is incorrect,” he said. “Consider a few sentences in an e-mail or text message as a substitute for the after-visit instructions from an office visit to enhance patient understanding. There are several inexpensive programs/services that allow text messages to be sent from a computer using a separate dedicated phone number and pretty much every patient has a cell phone to receive the instructions.”

Dr. Sullivan suggests having a documentation template specifically for telehealth visits. He also recommends the inclusion an “informed refusal of care” in the record when necessary. Dr. Sullivan’s wife, a family physician, has encountered several patients who fear contracting COVID-19 and who have refused her recommendations for in-person visits, he said. In such cases, he said it’s a good idea to document that the patient decided to forgo the recommendations given.

“If a patient suffers a bad outcome because of a failure to seek an in-person exam, a short note in the patient’s chart would help to establish that the lack of a follow-up physical exam was the patient’s informed decision, not due to some alleged negligence of the medical provider,” he said.

Concerning informed consent, Dr. Feldman says at a minimum physicians should discuss the following with patients:

• Names and credentials of staff participating.
• The right to stop or refuse treatment by telemedicine.
• Technology that will be used.
• Privacy and security risks.
• Technology-specific risks and permission to bill.
• Alternative care in case of an emergency or technology malfunction.
• Any state-specific requirements.

“Physicians can ensure they have a strong informed consent process during video visits by taking the time to cover these points at the beginning of the first visit, and being sure the patient understands and agrees to these,” Dr. Sullivan explained. “Ideally, this conversation can be recorded for future reference if necessary or at a minimum documented in the medical record.”
 

Consider these extra precautions

Mr. Cahill advises that practitioners be especially mindful of their “web-side manner” and the setting in which they are communicating with virtual patients to promote confidentiality, professionalism, and uninterrupted interactions.

“Use of a headset in a quiet home office is advisable,” he said. “Physicians must also be cognizant of their physical appearance and the background behind them when the visit includes both audio and visual capability. For ‘face-to-face’ telehealth encounters, it is recommended that a white lab jacket be worn as the appropriate attire; coat and tie are unnecessary.”

Some patients may need to be reminded of the need for confidentiality during a video visit, Mr. Moore added. Physicians are typically in a position to ensure confidentiality, but some patients may not understand how to protect their privacy on their end. 

“If the physician sees on the screen or hears from an audio connection that there are other people around who may be able to overhear what is communicated, the physician probably has some responsibility to remind the patient that she or he may want to go to a more private place, close the door, etc.,” he said. “While I think a claim against a physician on this basis would be pretty weak, it is still a good practice for the physician to be cognizant of those kinds of concerns even if the patient is not.”

Finally, for physicians who set up telehealth operability during the pandemic – possibly in a hurry – consider using your actual case data to take a look backward, said Ms. Lerman, the Washington-based health care attorney. Reviewing the data can help determine whether you’re in compliance with relevant state laws, she said. 

“If, for example, a provider set up telehealth operations during the pandemic and can see that most of [the] patients are based in a single state, or a small group of states, it is worthwhile to take [the] time and become familiar with the telemedicine laws in those states,” she said. “If there are modifications that need to be made, it may be easier to make them incrementally before the telehealth operations grow any larger in scope.” 

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

A new study has found that older patients who test positive for the cytotoxin associated gene-A (CagA) strain of Helicobacter pylori may be more at risk of both osteoporosis and fractures.

Patho/Wikimedia Commons/CC BY-SA 3.0

“Further studies will be required to replicate these findings in other cohorts and to better clarify the underlying pathogenetic mechanisms leading to increased bone fragility in subjects infected by CagA-positive H. pylori strains,” wrote Luigi Gennari, MD, PhD, of the University of Siena (Italy), and coauthors. The study was published in the Journal of Bone and Mineral Research.

To determine the effects of H. pylori on bone health and potential fracture risk, the researchers launched a population-based cohort study of 1,149 adults between the ages of 50 and 80 in Siena. The cohort comprised 174 males with an average (SD) age of 65.9 (plus or minus 6 years) and 975 females with an average age of 62.5 (plus or minus 6 years). All subjects were examined for H. pylori antibodies, and those who were infected were also examined for anti-CagA serum antibodies. As blood was sampled, bone mineral density (BMD) of the lumbar spine, femoral neck, total hip, and total body was measured via dual-energy x-ray absorptiometry.

In total, 53% of male participants and 49% of female participants tested positive for H. pylori, with CagA-positive strains found in 27% of males and 26% of females. No differences in infection rates were discovered in regard to socioeconomic status, age, weight, or height. Patients with normal BMD (45%), osteoporosis (51%), or osteopenia (49%) had similar prevalence of H. pylori infection, but CagA-positive strains were more frequently found in osteoporotic (30%) and osteopenic (26%) patients, compared to patients with normal BMD (21%, P < .01). CagA-positive female patients also had lower lumbar (0.950 g/cm²) and femoral (0.795 g/cm²) BMD, compared to CagA-negative (0.987 and 0.813 g/cm²) or H. pylori-negative women (0.997 and 0.821 g/cm²), respectively.

After an average follow-up period of 11.8 years, 199 nontraumatic fractures (72 vertebral and 127 nonvertebral) had occurred in 158 participants. Patients with CagA-positive strains of H. pylori had significantly increased risk of a clinical vertebral fracture (hazard ratio [HR], 5.27; 95% confidence interval, 2.23-12.63; P < .0001) or a nonvertebral incident fracture (HR, 2.09; 95% CI, 1.27-2.46; P < .01), compared to patients without H. pylori. After adjustment for age, sex, and body mass index, the risk among CagA-positive patients remained similarly significantly elevated for both vertebral (aHR, 4.78; 95% CI, 1.99-11.47; P < .0001) and nonvertebral fractures (aHR, 2.04; 95% CI, 1.22-3.41; P < .01).

The authors acknowledged their study’s limitations, including a cohort that was notably low in male participants, an inability to assess the effects of eradicating H. pylori on bone, and uncertainty as to which specific effects of H. pylori infection increase the risk of osteoporosis or fracture. Along those lines, they noted that an association between serum CagA antibody titer and gastric mucosal inflammation could lead to malabsorption of calcium, hypothesizing that antibody titer rather than antibody positivity “might be a more relevant marker for assessing the risk of bone fragility in patients affected by H. pylori infection.”

The study was supported in part by a grant from the Italian Association for Osteoporosis. The authors reported no potential conflicts of interest.

SOURCE: Gennari L et al. J Bone Miner Res. 2020 Aug 13. doi: 10.1002/jbmr.4162.

A new study has found that older patients who test positive for the cytotoxin associated gene-A (CagA) strain of Helicobacter pylori may be more at risk of both osteoporosis and fractures.

Patho/Wikimedia Commons/CC BY-SA 3.0

“Further studies will be required to replicate these findings in other cohorts and to better clarify the underlying pathogenetic mechanisms leading to increased bone fragility in subjects infected by CagA-positive H. pylori strains,” wrote Luigi Gennari, MD, PhD, of the University of Siena (Italy), and coauthors. The study was published in the Journal of Bone and Mineral Research.

To determine the effects of H. pylori on bone health and potential fracture risk, the researchers launched a population-based cohort study of 1,149 adults between the ages of 50 and 80 in Siena. The cohort comprised 174 males with an average (SD) age of 65.9 (plus or minus 6 years) and 975 females with an average age of 62.5 (plus or minus 6 years). All subjects were examined for H. pylori antibodies, and those who were infected were also examined for anti-CagA serum antibodies. As blood was sampled, bone mineral density (BMD) of the lumbar spine, femoral neck, total hip, and total body was measured via dual-energy x-ray absorptiometry.

In total, 53% of male participants and 49% of female participants tested positive for H. pylori, with CagA-positive strains found in 27% of males and 26% of females. No differences in infection rates were discovered in regard to socioeconomic status, age, weight, or height. Patients with normal BMD (45%), osteoporosis (51%), or osteopenia (49%) had similar prevalence of H. pylori infection, but CagA-positive strains were more frequently found in osteoporotic (30%) and osteopenic (26%) patients, compared to patients with normal BMD (21%, P < .01). CagA-positive female patients also had lower lumbar (0.950 g/cm²) and femoral (0.795 g/cm²) BMD, compared to CagA-negative (0.987 and 0.813 g/cm²) or H. pylori-negative women (0.997 and 0.821 g/cm²), respectively.

After an average follow-up period of 11.8 years, 199 nontraumatic fractures (72 vertebral and 127 nonvertebral) had occurred in 158 participants. Patients with CagA-positive strains of H. pylori had significantly increased risk of a clinical vertebral fracture (hazard ratio [HR], 5.27; 95% confidence interval, 2.23-12.63; P < .0001) or a nonvertebral incident fracture (HR, 2.09; 95% CI, 1.27-2.46; P < .01), compared to patients without H. pylori. After adjustment for age, sex, and body mass index, the risk among CagA-positive patients remained similarly significantly elevated for both vertebral (aHR, 4.78; 95% CI, 1.99-11.47; P < .0001) and nonvertebral fractures (aHR, 2.04; 95% CI, 1.22-3.41; P < .01).

The authors acknowledged their study’s limitations, including a cohort that was notably low in male participants, an inability to assess the effects of eradicating H. pylori on bone, and uncertainty as to which specific effects of H. pylori infection increase the risk of osteoporosis or fracture. Along those lines, they noted that an association between serum CagA antibody titer and gastric mucosal inflammation could lead to malabsorption of calcium, hypothesizing that antibody titer rather than antibody positivity “might be a more relevant marker for assessing the risk of bone fragility in patients affected by H. pylori infection.”

The study was supported in part by a grant from the Italian Association for Osteoporosis. The authors reported no potential conflicts of interest.

SOURCE: Gennari L et al. J Bone Miner Res. 2020 Aug 13. doi: 10.1002/jbmr.4162.

A new study has found that older patients who test positive for the cytotoxin associated gene-A (CagA) strain of Helicobacter pylori may be more at risk of both osteoporosis and fractures.

Patho/Wikimedia Commons/CC BY-SA 3.0

“Further studies will be required to replicate these findings in other cohorts and to better clarify the underlying pathogenetic mechanisms leading to increased bone fragility in subjects infected by CagA-positive H. pylori strains,” wrote Luigi Gennari, MD, PhD, of the University of Siena (Italy), and coauthors. The study was published in the Journal of Bone and Mineral Research.

To determine the effects of H. pylori on bone health and potential fracture risk, the researchers launched a population-based cohort study of 1,149 adults between the ages of 50 and 80 in Siena. The cohort comprised 174 males with an average (SD) age of 65.9 (plus or minus 6 years) and 975 females with an average age of 62.5 (plus or minus 6 years). All subjects were examined for H. pylori antibodies, and those who were infected were also examined for anti-CagA serum antibodies. As blood was sampled, bone mineral density (BMD) of the lumbar spine, femoral neck, total hip, and total body was measured via dual-energy x-ray absorptiometry.

In total, 53% of male participants and 49% of female participants tested positive for H. pylori, with CagA-positive strains found in 27% of males and 26% of females. No differences in infection rates were discovered in regard to socioeconomic status, age, weight, or height. Patients with normal BMD (45%), osteoporosis (51%), or osteopenia (49%) had similar prevalence of H. pylori infection, but CagA-positive strains were more frequently found in osteoporotic (30%) and osteopenic (26%) patients, compared to patients with normal BMD (21%, P < .01). CagA-positive female patients also had lower lumbar (0.950 g/cm²) and femoral (0.795 g/cm²) BMD, compared to CagA-negative (0.987 and 0.813 g/cm²) or H. pylori-negative women (0.997 and 0.821 g/cm²), respectively.

After an average follow-up period of 11.8 years, 199 nontraumatic fractures (72 vertebral and 127 nonvertebral) had occurred in 158 participants. Patients with CagA-positive strains of H. pylori had significantly increased risk of a clinical vertebral fracture (hazard ratio [HR], 5.27; 95% confidence interval, 2.23-12.63; P < .0001) or a nonvertebral incident fracture (HR, 2.09; 95% CI, 1.27-2.46; P < .01), compared to patients without H. pylori. After adjustment for age, sex, and body mass index, the risk among CagA-positive patients remained similarly significantly elevated for both vertebral (aHR, 4.78; 95% CI, 1.99-11.47; P < .0001) and nonvertebral fractures (aHR, 2.04; 95% CI, 1.22-3.41; P < .01).

The authors acknowledged their study’s limitations, including a cohort that was notably low in male participants, an inability to assess the effects of eradicating H. pylori on bone, and uncertainty as to which specific effects of H. pylori infection increase the risk of osteoporosis or fracture. Along those lines, they noted that an association between serum CagA antibody titer and gastric mucosal inflammation could lead to malabsorption of calcium, hypothesizing that antibody titer rather than antibody positivity “might be a more relevant marker for assessing the risk of bone fragility in patients affected by H. pylori infection.”

The study was supported in part by a grant from the Italian Association for Osteoporosis. The authors reported no potential conflicts of interest.

SOURCE: Gennari L et al. J Bone Miner Res. 2020 Aug 13. doi: 10.1002/jbmr.4162.

A new analysis of existing research confirms a stark link between excess weight and COVID-19: People with obesity are much more likely to be diagnosed with the novel coronavirus, undergo hospitalization and ICU admission, and die.

Obese patients faced the greatest bump in risk on the hospitalization front, with their odds of being admitted listed as 113% higher. The odds of diagnosis, ICU admission, and death were 46% higher (odds ratio [OR], 1.46; 95% confidence interval [CI], 1.30-1.65; P < .0001); 74% higher (OR, 1.74, CI, 1.46-2.08, P < .0001); 48% (OR, 1.48, CI, 1.22–1.80, P < .001, all pooled analyses and 95% CI), respectively. All differences were highly significantly different, investigators reported in a systematic review and meta-analysis published online Aug. 26 in Obesity Reviews.

“Essentially, these are pretty scary statistics,” nutrition researcher and study lead author Barry M. Popkin, PhD, of the University of North Carolina at Chapel Hill School of Public Health, said in an interview. “Other studies have talked about an increase in mortality, and we were thinking there’d be a little increase like 10% – nothing like 48%.”

According to the Johns Hopkins University of Medicine tracker, nearly 6 million people in the United States had been diagnosed with COVID-19 as of Aug. 30. The number of deaths had surpassed 183,000.

The authors of the new review launched their project to better understand the link between obesity and COVID-19 “all the way from being diagnosed to death,” Dr. Popkin said, adding that the meta-analysis is the largest of its kind to examine the link.

Dr. Popkin and colleagues analyzed 75 studies during January to June 2020 that tracked 399,461 patients (55% of whom were male) diagnosed with COVID-19. They found that 18 of 20 studies linked obesity with a 46% higher risk of diagnosis, but Dr. Popkin cautioned that this may be misleading. “I suspect it’s because they’re sicker and getting tested more for COVID,” he said. “I don’t think obesity enhances your likelihood of getting COVID. We don’t have a biological rationale for that.”

The researchers examined 19 studies that explored a link between obesity and hospitalization; all 19 found a higher risk of hospitalization in patients with obesity (pooled OR, 2.13). Twenty-one of 22 studies that looked at ICU admissions discovered a higher risk for patients with obesity (pooled OR, 1.74). And 27 of 35 studies that examined COVID-19 mortality found a higher death rate in patients with obesity (pooled OR, 1.48).

The review also looked at 14 studies that examined links between obesity and administration of invasive mechanical ventilation. All the studies found a higher risk for patients with obesity (pooled OR, 1.66; 95% CI, 1.38-1.99; P < .0001).

Could socioeconomic factors explain the difference in risk for people with obesity? It’s not clear. According to Dr. Popkin, most of the studies don’t examine factors such as income. While he believes physical factors are the key to the higher risk, he said “there’s clearly a social side to this.”

On the biological front, it appears that “the immune system is much weaker if you’re obese,” he said, and excess weight may worsen the course of a respiratory disease such as COVID-19 because of lung disorders such as sleep apnea.

In addition to highlighting inflammation and a weakened immune system, the review offers multiple explanations for why patients with obesity face worse outcomes in COVID-19. It may be more difficult for medical professionals to care for them in the hospital because of their weight, the authors wrote, and “obesity may also impair therapeutic treatments during COVID-19 infections.” The authors noted that ACE inhibitors may worsen COVID-19 in patients with type 2 diabetes.

The researchers noted that “potentially the vaccines developed to address COVID-19 will be less effective for individuals with obesity due to a weakened immune response.” They pointed to research that suggests T-cell responses are weaker and antibody titers wane at a faster rate in people with obesity who are vaccinated against influenza.