MDedge Infectious Disease

Pursuing fellowship training is often financially costly in terms of lifetime earnings, compared with starting a career as a general pediatrician immediately after residency, a report suggests.

Researchers found that most pediatric subspecialists – including those practicing neurology, pulmonology, and adolescent medicine – do not see a financial return from additional training because of the delays in receiving increased compensation and the repayment of educational debt.

“Most pediatric subspecialists don’t experience a relative increase in compensation after training compared to a general pediatrician, so there isn’t a financial benefit to additional training,” lead author Eva Catenaccio, MD, from the division of pediatric neurology, department of neurology, Johns Hopkins University, Baltimore, told this news organization.

The findings, published online March 8 in Pediatrics, contribute to the ongoing debate about the length of pediatric fellowship training programs. The data also provide evidence for the potential effect of a pediatric subspecialty loan repayment program.
 

Pediatric subspecialty training rarely pays off

However, not all practitioners in pediatric subspecialties would find themselves in the red relative to their generalist peers. Three subspecialties had a positive financial return: cardiology, critical care, and neonatology. Dr. Catenaccio explained that this may be because these subspecialties tend to be “inpatient procedure oriented, which are often more [lucrative] than outpatient cognitive–oriented subspecialties, such as pediatric infectious diseases, endocrinology, or adolescent medicine.”

Enrolling in a pediatric fellowship program resulted in lifetime financial returns that ranged from an increase of $852,129 for cardiology, relative to general pediatrics, to a loss of $1,594,366 for adolescent medicine, researchers found.

For the study, researchers calculated the financial returns of 15 pediatric subspecialties – emergency medicine, neurology, cardiology, critical care, neonatology, hematology and oncology, pulmonology, hospitalist medicine, allergy and immunology, gastroenterology, rheumatology, nephrology, adolescent medicine, infectious diseases, and endocrinology – in comparison with returns of private practice general pediatrics on the basis of 2018-2019 data on fellowship stipends, compensation, and educational debt.

They obtained most of the data from the Association of American Medical Colleges Survey of Resident/Fellow Stipends and Benefits, AAMC’s annual Medical School Faculty Salary Report, and the AAMC Medical School Graduation Questionnaire.

Richard Mink, MD, department of pediatrics, Harbor-UCLA Medical Center, Torrance, Calif., noted that it would have been helpful to have also compared the lifetime earnings of practitioners in pediatric subspecialties to academic general pediatricians and not just those in private practice.
 

The financial gap has worsened

To better understand which aspects of fellowship training have the greatest effect on lifetime compensation, Dr. Catenaccio and colleagues evaluated the potential effects of shortening fellowship length, eliminating school debt, and implementing a federal loan repayment plan. These changes enhanced the returns of cardiology, critical care, and neonatology – subspecialties that had already seen financial returns before these changes – and resulted in a positive financial return for emergency medicine.

The changes also narrowed the financial gap between subspecialties and general pediatrics. However, the remaining subspecialties still earned less than private practice pediatrics.

The new study is an update to a 2011 report, which reflected 2007-2008 data for 11 subspecialties. This time around, the researchers included the subspecialty of hospitalist medicine, which was approved as a board-certified subspecialty by the American Board of Pediatrics in 2014, as well as neurology, allergy and immunology, and adolescent medicine.

“I was most surprised that the additional pediatric subspecialties we included since the 2011 report followed the same general trend, with pediatric subspecialty training having a lower lifetime earning potential than general pediatrics,” Dr. Catenaccio said.

Comparing results from the two study periods showed that the financial gap between general pediatrics and subspecialty pediatrics worsened over time. For example, the financial return for pediatric endocrinology decreased an additional $500,000 between 2007 and 2018.

The researchers believe a combination of increased educational debt burden, slow growth in compensation, and changing interest rates over time have caused the financial differences between general pediatrics and subspecialty pediatrics to become more pronounced.
 

‘Pediatric subspecialty training is worth it!’

Despite the financial gaps, Dr. Catenaccio and colleagues say pediatric subspecialty training is still worthwhile but that policymakers should address these financial differences to help guide workforce distribution in a way that meets the needs of patients.

“I think pediatric subspecialty training is worth it,” said Dr. Catenaccio, who’s pursuing pediatric subspecialty training. “There are so many factors that go into choosing a specialty or subspecialty in medicine, including the desire to care for a particular patient population, interest in certain diseases or organ systems, lifestyle considerations, and research opportunities.”

But it’s also important for trainees to be aware of economic considerations in their decision-making.

Dr. Mink, who wrote an accompanying commentary, agrees that young clinicians should not make career decisions on the basis of metrics such as lifetime earning measures.

“I think people who go into pediatrics have decided that money is not the driving force,” said Dr. Mink. He noted that pediatricians are usually not paid well, compared with other specialists. “To me the important thing is you have to like what you’re doing.”

A 2020 study found that trainees who chose a career in pediatric pulmonology, a subspecialty, said that financial considerations were not the driving factor in their decision-making. Nevertheless, Dr. Mink also believes young clinicians should take into account their educational debt.

The further widening of the financial gap between general pediatrics and pediatric subspecialties could lead to shortages in the pediatric subspecialty workforce.

The authors and Dr. Mink have disclosed no relevant financial relationships.

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

Pursuing fellowship training is often financially costly in terms of lifetime earnings, compared with starting a career as a general pediatrician immediately after residency, a report suggests.

Researchers found that most pediatric subspecialists – including those practicing neurology, pulmonology, and adolescent medicine – do not see a financial return from additional training because of the delays in receiving increased compensation and the repayment of educational debt.

“Most pediatric subspecialists don’t experience a relative increase in compensation after training compared to a general pediatrician, so there isn’t a financial benefit to additional training,” lead author Eva Catenaccio, MD, from the division of pediatric neurology, department of neurology, Johns Hopkins University, Baltimore, told this news organization.

The findings, published online March 8 in Pediatrics, contribute to the ongoing debate about the length of pediatric fellowship training programs. The data also provide evidence for the potential effect of a pediatric subspecialty loan repayment program.
 

Pediatric subspecialty training rarely pays off

However, not all practitioners in pediatric subspecialties would find themselves in the red relative to their generalist peers. Three subspecialties had a positive financial return: cardiology, critical care, and neonatology. Dr. Catenaccio explained that this may be because these subspecialties tend to be “inpatient procedure oriented, which are often more [lucrative] than outpatient cognitive–oriented subspecialties, such as pediatric infectious diseases, endocrinology, or adolescent medicine.”

Enrolling in a pediatric fellowship program resulted in lifetime financial returns that ranged from an increase of $852,129 for cardiology, relative to general pediatrics, to a loss of $1,594,366 for adolescent medicine, researchers found.

For the study, researchers calculated the financial returns of 15 pediatric subspecialties – emergency medicine, neurology, cardiology, critical care, neonatology, hematology and oncology, pulmonology, hospitalist medicine, allergy and immunology, gastroenterology, rheumatology, nephrology, adolescent medicine, infectious diseases, and endocrinology – in comparison with returns of private practice general pediatrics on the basis of 2018-2019 data on fellowship stipends, compensation, and educational debt.

They obtained most of the data from the Association of American Medical Colleges Survey of Resident/Fellow Stipends and Benefits, AAMC’s annual Medical School Faculty Salary Report, and the AAMC Medical School Graduation Questionnaire.

Richard Mink, MD, department of pediatrics, Harbor-UCLA Medical Center, Torrance, Calif., noted that it would have been helpful to have also compared the lifetime earnings of practitioners in pediatric subspecialties to academic general pediatricians and not just those in private practice.
 

The financial gap has worsened

To better understand which aspects of fellowship training have the greatest effect on lifetime compensation, Dr. Catenaccio and colleagues evaluated the potential effects of shortening fellowship length, eliminating school debt, and implementing a federal loan repayment plan. These changes enhanced the returns of cardiology, critical care, and neonatology – subspecialties that had already seen financial returns before these changes – and resulted in a positive financial return for emergency medicine.

The changes also narrowed the financial gap between subspecialties and general pediatrics. However, the remaining subspecialties still earned less than private practice pediatrics.

The new study is an update to a 2011 report, which reflected 2007-2008 data for 11 subspecialties. This time around, the researchers included the subspecialty of hospitalist medicine, which was approved as a board-certified subspecialty by the American Board of Pediatrics in 2014, as well as neurology, allergy and immunology, and adolescent medicine.

“I was most surprised that the additional pediatric subspecialties we included since the 2011 report followed the same general trend, with pediatric subspecialty training having a lower lifetime earning potential than general pediatrics,” Dr. Catenaccio said.

Comparing results from the two study periods showed that the financial gap between general pediatrics and subspecialty pediatrics worsened over time. For example, the financial return for pediatric endocrinology decreased an additional $500,000 between 2007 and 2018.

The researchers believe a combination of increased educational debt burden, slow growth in compensation, and changing interest rates over time have caused the financial differences between general pediatrics and subspecialty pediatrics to become more pronounced.
 

‘Pediatric subspecialty training is worth it!’

Despite the financial gaps, Dr. Catenaccio and colleagues say pediatric subspecialty training is still worthwhile but that policymakers should address these financial differences to help guide workforce distribution in a way that meets the needs of patients.

“I think pediatric subspecialty training is worth it,” said Dr. Catenaccio, who’s pursuing pediatric subspecialty training. “There are so many factors that go into choosing a specialty or subspecialty in medicine, including the desire to care for a particular patient population, interest in certain diseases or organ systems, lifestyle considerations, and research opportunities.”

But it’s also important for trainees to be aware of economic considerations in their decision-making.

Dr. Mink, who wrote an accompanying commentary, agrees that young clinicians should not make career decisions on the basis of metrics such as lifetime earning measures.

“I think people who go into pediatrics have decided that money is not the driving force,” said Dr. Mink. He noted that pediatricians are usually not paid well, compared with other specialists. “To me the important thing is you have to like what you’re doing.”

A 2020 study found that trainees who chose a career in pediatric pulmonology, a subspecialty, said that financial considerations were not the driving factor in their decision-making. Nevertheless, Dr. Mink also believes young clinicians should take into account their educational debt.

The further widening of the financial gap between general pediatrics and pediatric subspecialties could lead to shortages in the pediatric subspecialty workforce.

The authors and Dr. Mink have disclosed no relevant financial relationships.

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

Pursuing fellowship training is often financially costly in terms of lifetime earnings, compared with starting a career as a general pediatrician immediately after residency, a report suggests.

Researchers found that most pediatric subspecialists – including those practicing neurology, pulmonology, and adolescent medicine – do not see a financial return from additional training because of the delays in receiving increased compensation and the repayment of educational debt.

“Most pediatric subspecialists don’t experience a relative increase in compensation after training compared to a general pediatrician, so there isn’t a financial benefit to additional training,” lead author Eva Catenaccio, MD, from the division of pediatric neurology, department of neurology, Johns Hopkins University, Baltimore, told this news organization.

The findings, published online March 8 in Pediatrics, contribute to the ongoing debate about the length of pediatric fellowship training programs. The data also provide evidence for the potential effect of a pediatric subspecialty loan repayment program.
 

Pediatric subspecialty training rarely pays off

However, not all practitioners in pediatric subspecialties would find themselves in the red relative to their generalist peers. Three subspecialties had a positive financial return: cardiology, critical care, and neonatology. Dr. Catenaccio explained that this may be because these subspecialties tend to be “inpatient procedure oriented, which are often more [lucrative] than outpatient cognitive–oriented subspecialties, such as pediatric infectious diseases, endocrinology, or adolescent medicine.”

Enrolling in a pediatric fellowship program resulted in lifetime financial returns that ranged from an increase of $852,129 for cardiology, relative to general pediatrics, to a loss of $1,594,366 for adolescent medicine, researchers found.

For the study, researchers calculated the financial returns of 15 pediatric subspecialties – emergency medicine, neurology, cardiology, critical care, neonatology, hematology and oncology, pulmonology, hospitalist medicine, allergy and immunology, gastroenterology, rheumatology, nephrology, adolescent medicine, infectious diseases, and endocrinology – in comparison with returns of private practice general pediatrics on the basis of 2018-2019 data on fellowship stipends, compensation, and educational debt.

They obtained most of the data from the Association of American Medical Colleges Survey of Resident/Fellow Stipends and Benefits, AAMC’s annual Medical School Faculty Salary Report, and the AAMC Medical School Graduation Questionnaire.

Richard Mink, MD, department of pediatrics, Harbor-UCLA Medical Center, Torrance, Calif., noted that it would have been helpful to have also compared the lifetime earnings of practitioners in pediatric subspecialties to academic general pediatricians and not just those in private practice.
 

The financial gap has worsened

To better understand which aspects of fellowship training have the greatest effect on lifetime compensation, Dr. Catenaccio and colleagues evaluated the potential effects of shortening fellowship length, eliminating school debt, and implementing a federal loan repayment plan. These changes enhanced the returns of cardiology, critical care, and neonatology – subspecialties that had already seen financial returns before these changes – and resulted in a positive financial return for emergency medicine.

The changes also narrowed the financial gap between subspecialties and general pediatrics. However, the remaining subspecialties still earned less than private practice pediatrics.

The new study is an update to a 2011 report, which reflected 2007-2008 data for 11 subspecialties. This time around, the researchers included the subspecialty of hospitalist medicine, which was approved as a board-certified subspecialty by the American Board of Pediatrics in 2014, as well as neurology, allergy and immunology, and adolescent medicine.

“I was most surprised that the additional pediatric subspecialties we included since the 2011 report followed the same general trend, with pediatric subspecialty training having a lower lifetime earning potential than general pediatrics,” Dr. Catenaccio said.

Comparing results from the two study periods showed that the financial gap between general pediatrics and subspecialty pediatrics worsened over time. For example, the financial return for pediatric endocrinology decreased an additional $500,000 between 2007 and 2018.

The researchers believe a combination of increased educational debt burden, slow growth in compensation, and changing interest rates over time have caused the financial differences between general pediatrics and subspecialty pediatrics to become more pronounced.
 

‘Pediatric subspecialty training is worth it!’

Despite the financial gaps, Dr. Catenaccio and colleagues say pediatric subspecialty training is still worthwhile but that policymakers should address these financial differences to help guide workforce distribution in a way that meets the needs of patients.

“I think pediatric subspecialty training is worth it,” said Dr. Catenaccio, who’s pursuing pediatric subspecialty training. “There are so many factors that go into choosing a specialty or subspecialty in medicine, including the desire to care for a particular patient population, interest in certain diseases or organ systems, lifestyle considerations, and research opportunities.”

But it’s also important for trainees to be aware of economic considerations in their decision-making.

Dr. Mink, who wrote an accompanying commentary, agrees that young clinicians should not make career decisions on the basis of metrics such as lifetime earning measures.

“I think people who go into pediatrics have decided that money is not the driving force,” said Dr. Mink. He noted that pediatricians are usually not paid well, compared with other specialists. “To me the important thing is you have to like what you’re doing.”

A 2020 study found that trainees who chose a career in pediatric pulmonology, a subspecialty, said that financial considerations were not the driving factor in their decision-making. Nevertheless, Dr. Mink also believes young clinicians should take into account their educational debt.

The further widening of the financial gap between general pediatrics and pediatric subspecialties could lead to shortages in the pediatric subspecialty workforce.

The authors and Dr. Mink have disclosed no relevant financial relationships.

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

Pregnant patients with COVID-19 infections were more likely to experience severe disease if they had preexisting comorbidities, such as chronic hypertension, asthma, or pregestational diabetes, according to findings from a new study presented at the meeting sponsored by the Society for Maternal-Fetal Medicine.

The study included outcomes for the largest multistate cohort of pregnant patients with COVID-19 outside of what the Centers for Disease Control and Prevention is tracking. Its findings also mirrored those of a multicenter, retrospective study in Washington state, published in the American Journal of Obstetrics & Gynecology. That study also found that pregnant patients hospitalized for COVID-19 were more likely to have comorbidities, and both studies found an increased likelihood of preterm birth among pregnant patients with severe or critical disease.
 

Disease severity linked to risk of perinatal complications

In the abstract presented at the SMFM meeting, more severe disease was associated with older age and a higher median body mass index, as seen in the general population, but the researchers found no differences in disease severity occurred by race or ethnicity, Torri D. Metz, MD, of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network, told attendees of the conference. The researchers also found that perinatal complications were more prevalent in those with severe or critical COVID-19 disease but not in those with mild or moderate disease. Vertical COVID-19 transmission from mother to child was rare.

The observational study included all patients who had a singleton pregnancy, had a positive SARS-CoV-2 test, and delivered between March 1 and July 31, 2020, at one of the 33 U.S. hospitals in the NICHD Maternal-Fetal Medicine Units Network, spread across 14 states. The researchers used electronic medical records to determine incidence of cesarean delivery, postpartum hemorrhage, hypertensive disorders of pregnancy, preterm birth (less than 37 weeks), maternal death, infant death, and positive infant COVID-19 test. They tracked mothers through 6 weeks post partum and newborns through delivery hospitalization.

Of 1,291 patients in the cohort, 1,219 received their first positive COVID-19 test during pregnancy. The others tested positive while in the hospital for delivery or within a month and a half after discharge. Limiting their analysis to those who developed COVID-19 while pregnant prior to delivery, nearly half (47%) were asymptomatic.

The disease was mild in 27%, moderate in 14%, severe in 8%, and critical in 4%. The researchers used the National Institutes of Health classifications for severity and included deaths in the critical group. The most common symptom was a cough, reported by a third of the patients (34%). Four of six maternal deaths that occurred were caused by COVID-19.

Compared with an average age of 28 in those without symptoms, the mean age was 29 in those with mild/moderate disease and 30 in those with severe/critical disease (P = .006). Similarly, the mean BMI was 28.3 in asymptomatic patients, 29 in those with mild/moderate disease, and 32.3 in those with severe/critical disease (P < .001). Despite a diverse cohort – 53% Hispanic, 23% Black, and 15% White – the researches found no racial/ethnic trends in disease severity.

Patients who had asthma, chronic obstructive pulmonary disorder, pregestational diabetes, chronic hypertension, chronic liver disease, or a seizure disorder were all significantly more likely to have critical/severe disease than mild/moderate disease, and more likely to have mild/moderate disease than asymptomatic (P values ranged from < .001 to .02).

The mothers with critical or severe illness were 1.6 times more likely to have cesarean births and to have hypertensive disorders of pregnancy, and they were twice as likely to have postpartum hemorrhage (P < .001; P = .007). Those with mild or moderate disease, however, had no increased risks for perinatal complications over asymptomatic patients.

Critical or severe illness was also associated with more than triple the risk of preterm birth (adjusted risk ratio, 3.6; P < .001). Newborns of mothers with critical or severe illness also had three times greater risk of neonatal ICU admission (ARR, 3.1; P <. 001) and weighed an average 385 g less than newborns of asymptomatic mothers. COVID-19 rate among infants was only 1% during delivery hospitalization.

Since the study cutoff was July 30 and COVID infections only became prevalent in March, the researchers were unable to evaluate women for outcomes resulting from COVID infections in early pregnancy, such as congenital anomalies or early miscarriage, Dr. Metz said. In addition, since many of the sites are urban centers, the data may not be generalizable to rural areas.

Peter S. Bernstein, MD, MPH, of Montefiore Medical Center, New York, asked whether the increased cesarean deliveries and preterm births in the group of women with severe disease were caused by usual obstetric causes or the treatment of COVID-19 infection. Dr. Metz said the vast majority of preterm deliveries were indicated, but only a small proportion were induced for COVID-19 alone. “A lot had hypertensive disorders of pregnancies or PPROM, so it’s partly driven by the infection itself but also partly driven by some of those perinatal complications,” she said.
 

Similar findings in Washington

In the Washington study, among 240 pregnant patients with confirmed COVID-19 infection between March 1 and July 30, 2020, 1 in 11 developed severe or critical disease, and 1 in 10 were hospitalized. The pregnant patients had more than triple the risk of hospitalization compared with adults of similar ages in the general population (10% vs. 2.8%; rate ratio, 3.5). Similar to the multistate NICHD study, women were more likely to be hospitalized if they had asthma, hypertension, type 2 diabetes, autoimmune disease, or class III obesity.

Three mothers died of COVID-19, resulting in a case fatality rate 13.6 times greater than nonpregnant patients with COVID-19 in the general population. The absolute difference in the rate was 1.2%. As seen in the NICHD study, preterm birth was more common in mothers with severe or critical COVID-19. Nearly half (45.4%) of mothers with severe or critical COVID-19 delivered preterm compared to 5.2% in those with mild COVID-19 (P < .001).

“Our finding that deaths in pregnant patients contributed disproportionately to deaths from COVID-19 among 20- to 39-year-olds in Washington state is similar to what was observed during the influenza A virus H1N1 2009 pandemic,” Erica M. Lokken, PhD, MS, of the departments of global health and ob.gyn. at the University of Washington, Seattle, and colleagues wrote in the Washington study. But they noted that it took 8 months into the pandemic before pregnant patients were identified as a high-risk group for COVID-19.

“Given the similarity in clinical course between COVID-19 and IAV H1N1 2009 with an increased risk for mortality during pregnancy and the postpartum period, we strongly recommend that pregnant patients should be considered a high-risk population to novel highly pathogenic respiratory viruses until proven otherwise by population-based studies with good ascertainment of pregnancy status,” they wrote.

Judette Louis, MD, MPH, associate professor of ob.gyn. and department chair at the University of South Florida, Tampa, said in an interview that the findings in these studies were fairly expected, but it’s important to have data from such a large cohort as the one presented at SMFM.

“It confirmed that those who had severe disease were more likely to have chronic medical conditions, mirroring what we saw in the general population who isn’t pregnant,” Dr. Louis said. “I thought this was very crucial because as pregnant women are trying to decide whether they should get the COVID vaccine, this provides support to say that if you’re pregnant, you’re more likely to have severe disease [if you have] other chronic medical conditions.”

The findings also confirm the importance of pregnant people taking precautions to avoid infection.

“Even though these individuals are, as a group, in an age cohort that mostly has asymptomatic disease, for some of them, it results in severe disease and even maternal death,” she said. “They should still take it seriously if they’re pregnant.”

The SMFM abstract study was funded by the NICHD. The Washington study was funded by the University of Washington Population Health Initiative, the National Institutes of Health, and philanthropic gift funds. One coauthor of the Washington study is on a Pfizer and GlaxoSmithKline advisory board for immunizations. No other authors or individuals interviewed reported any disclosures.

Pregnant patients with COVID-19 infections were more likely to experience severe disease if they had preexisting comorbidities, such as chronic hypertension, asthma, or pregestational diabetes, according to findings from a new study presented at the meeting sponsored by the Society for Maternal-Fetal Medicine.

The study included outcomes for the largest multistate cohort of pregnant patients with COVID-19 outside of what the Centers for Disease Control and Prevention is tracking. Its findings also mirrored those of a multicenter, retrospective study in Washington state, published in the American Journal of Obstetrics & Gynecology. That study also found that pregnant patients hospitalized for COVID-19 were more likely to have comorbidities, and both studies found an increased likelihood of preterm birth among pregnant patients with severe or critical disease.
 

Disease severity linked to risk of perinatal complications

In the abstract presented at the SMFM meeting, more severe disease was associated with older age and a higher median body mass index, as seen in the general population, but the researchers found no differences in disease severity occurred by race or ethnicity, Torri D. Metz, MD, of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network, told attendees of the conference. The researchers also found that perinatal complications were more prevalent in those with severe or critical COVID-19 disease but not in those with mild or moderate disease. Vertical COVID-19 transmission from mother to child was rare.

The observational study included all patients who had a singleton pregnancy, had a positive SARS-CoV-2 test, and delivered between March 1 and July 31, 2020, at one of the 33 U.S. hospitals in the NICHD Maternal-Fetal Medicine Units Network, spread across 14 states. The researchers used electronic medical records to determine incidence of cesarean delivery, postpartum hemorrhage, hypertensive disorders of pregnancy, preterm birth (less than 37 weeks), maternal death, infant death, and positive infant COVID-19 test. They tracked mothers through 6 weeks post partum and newborns through delivery hospitalization.

Of 1,291 patients in the cohort, 1,219 received their first positive COVID-19 test during pregnancy. The others tested positive while in the hospital for delivery or within a month and a half after discharge. Limiting their analysis to those who developed COVID-19 while pregnant prior to delivery, nearly half (47%) were asymptomatic.

The disease was mild in 27%, moderate in 14%, severe in 8%, and critical in 4%. The researchers used the National Institutes of Health classifications for severity and included deaths in the critical group. The most common symptom was a cough, reported by a third of the patients (34%). Four of six maternal deaths that occurred were caused by COVID-19.

Compared with an average age of 28 in those without symptoms, the mean age was 29 in those with mild/moderate disease and 30 in those with severe/critical disease (P = .006). Similarly, the mean BMI was 28.3 in asymptomatic patients, 29 in those with mild/moderate disease, and 32.3 in those with severe/critical disease (P < .001). Despite a diverse cohort – 53% Hispanic, 23% Black, and 15% White – the researches found no racial/ethnic trends in disease severity.

Patients who had asthma, chronic obstructive pulmonary disorder, pregestational diabetes, chronic hypertension, chronic liver disease, or a seizure disorder were all significantly more likely to have critical/severe disease than mild/moderate disease, and more likely to have mild/moderate disease than asymptomatic (P values ranged from < .001 to .02).

The mothers with critical or severe illness were 1.6 times more likely to have cesarean births and to have hypertensive disorders of pregnancy, and they were twice as likely to have postpartum hemorrhage (P < .001; P = .007). Those with mild or moderate disease, however, had no increased risks for perinatal complications over asymptomatic patients.

Critical or severe illness was also associated with more than triple the risk of preterm birth (adjusted risk ratio, 3.6; P < .001). Newborns of mothers with critical or severe illness also had three times greater risk of neonatal ICU admission (ARR, 3.1; P <. 001) and weighed an average 385 g less than newborns of asymptomatic mothers. COVID-19 rate among infants was only 1% during delivery hospitalization.

Since the study cutoff was July 30 and COVID infections only became prevalent in March, the researchers were unable to evaluate women for outcomes resulting from COVID infections in early pregnancy, such as congenital anomalies or early miscarriage, Dr. Metz said. In addition, since many of the sites are urban centers, the data may not be generalizable to rural areas.

Peter S. Bernstein, MD, MPH, of Montefiore Medical Center, New York, asked whether the increased cesarean deliveries and preterm births in the group of women with severe disease were caused by usual obstetric causes or the treatment of COVID-19 infection. Dr. Metz said the vast majority of preterm deliveries were indicated, but only a small proportion were induced for COVID-19 alone. “A lot had hypertensive disorders of pregnancies or PPROM, so it’s partly driven by the infection itself but also partly driven by some of those perinatal complications,” she said.
 

Similar findings in Washington

In the Washington study, among 240 pregnant patients with confirmed COVID-19 infection between March 1 and July 30, 2020, 1 in 11 developed severe or critical disease, and 1 in 10 were hospitalized. The pregnant patients had more than triple the risk of hospitalization compared with adults of similar ages in the general population (10% vs. 2.8%; rate ratio, 3.5). Similar to the multistate NICHD study, women were more likely to be hospitalized if they had asthma, hypertension, type 2 diabetes, autoimmune disease, or class III obesity.

Three mothers died of COVID-19, resulting in a case fatality rate 13.6 times greater than nonpregnant patients with COVID-19 in the general population. The absolute difference in the rate was 1.2%. As seen in the NICHD study, preterm birth was more common in mothers with severe or critical COVID-19. Nearly half (45.4%) of mothers with severe or critical COVID-19 delivered preterm compared to 5.2% in those with mild COVID-19 (P < .001).

“Our finding that deaths in pregnant patients contributed disproportionately to deaths from COVID-19 among 20- to 39-year-olds in Washington state is similar to what was observed during the influenza A virus H1N1 2009 pandemic,” Erica M. Lokken, PhD, MS, of the departments of global health and ob.gyn. at the University of Washington, Seattle, and colleagues wrote in the Washington study. But they noted that it took 8 months into the pandemic before pregnant patients were identified as a high-risk group for COVID-19.

“Given the similarity in clinical course between COVID-19 and IAV H1N1 2009 with an increased risk for mortality during pregnancy and the postpartum period, we strongly recommend that pregnant patients should be considered a high-risk population to novel highly pathogenic respiratory viruses until proven otherwise by population-based studies with good ascertainment of pregnancy status,” they wrote.

Judette Louis, MD, MPH, associate professor of ob.gyn. and department chair at the University of South Florida, Tampa, said in an interview that the findings in these studies were fairly expected, but it’s important to have data from such a large cohort as the one presented at SMFM.

“It confirmed that those who had severe disease were more likely to have chronic medical conditions, mirroring what we saw in the general population who isn’t pregnant,” Dr. Louis said. “I thought this was very crucial because as pregnant women are trying to decide whether they should get the COVID vaccine, this provides support to say that if you’re pregnant, you’re more likely to have severe disease [if you have] other chronic medical conditions.”

The findings also confirm the importance of pregnant people taking precautions to avoid infection.

“Even though these individuals are, as a group, in an age cohort that mostly has asymptomatic disease, for some of them, it results in severe disease and even maternal death,” she said. “They should still take it seriously if they’re pregnant.”

The SMFM abstract study was funded by the NICHD. The Washington study was funded by the University of Washington Population Health Initiative, the National Institutes of Health, and philanthropic gift funds. One coauthor of the Washington study is on a Pfizer and GlaxoSmithKline advisory board for immunizations. No other authors or individuals interviewed reported any disclosures.

Pregnant patients with COVID-19 infections were more likely to experience severe disease if they had preexisting comorbidities, such as chronic hypertension, asthma, or pregestational diabetes, according to findings from a new study presented at the meeting sponsored by the Society for Maternal-Fetal Medicine.

The study included outcomes for the largest multistate cohort of pregnant patients with COVID-19 outside of what the Centers for Disease Control and Prevention is tracking. Its findings also mirrored those of a multicenter, retrospective study in Washington state, published in the American Journal of Obstetrics & Gynecology. That study also found that pregnant patients hospitalized for COVID-19 were more likely to have comorbidities, and both studies found an increased likelihood of preterm birth among pregnant patients with severe or critical disease.
 

Disease severity linked to risk of perinatal complications

In the abstract presented at the SMFM meeting, more severe disease was associated with older age and a higher median body mass index, as seen in the general population, but the researchers found no differences in disease severity occurred by race or ethnicity, Torri D. Metz, MD, of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network, told attendees of the conference. The researchers also found that perinatal complications were more prevalent in those with severe or critical COVID-19 disease but not in those with mild or moderate disease. Vertical COVID-19 transmission from mother to child was rare.

The observational study included all patients who had a singleton pregnancy, had a positive SARS-CoV-2 test, and delivered between March 1 and July 31, 2020, at one of the 33 U.S. hospitals in the NICHD Maternal-Fetal Medicine Units Network, spread across 14 states. The researchers used electronic medical records to determine incidence of cesarean delivery, postpartum hemorrhage, hypertensive disorders of pregnancy, preterm birth (less than 37 weeks), maternal death, infant death, and positive infant COVID-19 test. They tracked mothers through 6 weeks post partum and newborns through delivery hospitalization.

Of 1,291 patients in the cohort, 1,219 received their first positive COVID-19 test during pregnancy. The others tested positive while in the hospital for delivery or within a month and a half after discharge. Limiting their analysis to those who developed COVID-19 while pregnant prior to delivery, nearly half (47%) were asymptomatic.

The disease was mild in 27%, moderate in 14%, severe in 8%, and critical in 4%. The researchers used the National Institutes of Health classifications for severity and included deaths in the critical group. The most common symptom was a cough, reported by a third of the patients (34%). Four of six maternal deaths that occurred were caused by COVID-19.

Compared with an average age of 28 in those without symptoms, the mean age was 29 in those with mild/moderate disease and 30 in those with severe/critical disease (P = .006). Similarly, the mean BMI was 28.3 in asymptomatic patients, 29 in those with mild/moderate disease, and 32.3 in those with severe/critical disease (P < .001). Despite a diverse cohort – 53% Hispanic, 23% Black, and 15% White – the researches found no racial/ethnic trends in disease severity.

Patients who had asthma, chronic obstructive pulmonary disorder, pregestational diabetes, chronic hypertension, chronic liver disease, or a seizure disorder were all significantly more likely to have critical/severe disease than mild/moderate disease, and more likely to have mild/moderate disease than asymptomatic (P values ranged from < .001 to .02).

The mothers with critical or severe illness were 1.6 times more likely to have cesarean births and to have hypertensive disorders of pregnancy, and they were twice as likely to have postpartum hemorrhage (P < .001; P = .007). Those with mild or moderate disease, however, had no increased risks for perinatal complications over asymptomatic patients.

Critical or severe illness was also associated with more than triple the risk of preterm birth (adjusted risk ratio, 3.6; P < .001). Newborns of mothers with critical or severe illness also had three times greater risk of neonatal ICU admission (ARR, 3.1; P <. 001) and weighed an average 385 g less than newborns of asymptomatic mothers. COVID-19 rate among infants was only 1% during delivery hospitalization.

Since the study cutoff was July 30 and COVID infections only became prevalent in March, the researchers were unable to evaluate women for outcomes resulting from COVID infections in early pregnancy, such as congenital anomalies or early miscarriage, Dr. Metz said. In addition, since many of the sites are urban centers, the data may not be generalizable to rural areas.

Peter S. Bernstein, MD, MPH, of Montefiore Medical Center, New York, asked whether the increased cesarean deliveries and preterm births in the group of women with severe disease were caused by usual obstetric causes or the treatment of COVID-19 infection. Dr. Metz said the vast majority of preterm deliveries were indicated, but only a small proportion were induced for COVID-19 alone. “A lot had hypertensive disorders of pregnancies or PPROM, so it’s partly driven by the infection itself but also partly driven by some of those perinatal complications,” she said.
 

Similar findings in Washington

In the Washington study, among 240 pregnant patients with confirmed COVID-19 infection between March 1 and July 30, 2020, 1 in 11 developed severe or critical disease, and 1 in 10 were hospitalized. The pregnant patients had more than triple the risk of hospitalization compared with adults of similar ages in the general population (10% vs. 2.8%; rate ratio, 3.5). Similar to the multistate NICHD study, women were more likely to be hospitalized if they had asthma, hypertension, type 2 diabetes, autoimmune disease, or class III obesity.

Three mothers died of COVID-19, resulting in a case fatality rate 13.6 times greater than nonpregnant patients with COVID-19 in the general population. The absolute difference in the rate was 1.2%. As seen in the NICHD study, preterm birth was more common in mothers with severe or critical COVID-19. Nearly half (45.4%) of mothers with severe or critical COVID-19 delivered preterm compared to 5.2% in those with mild COVID-19 (P < .001).

“Our finding that deaths in pregnant patients contributed disproportionately to deaths from COVID-19 among 20- to 39-year-olds in Washington state is similar to what was observed during the influenza A virus H1N1 2009 pandemic,” Erica M. Lokken, PhD, MS, of the departments of global health and ob.gyn. at the University of Washington, Seattle, and colleagues wrote in the Washington study. But they noted that it took 8 months into the pandemic before pregnant patients were identified as a high-risk group for COVID-19.

“Given the similarity in clinical course between COVID-19 and IAV H1N1 2009 with an increased risk for mortality during pregnancy and the postpartum period, we strongly recommend that pregnant patients should be considered a high-risk population to novel highly pathogenic respiratory viruses until proven otherwise by population-based studies with good ascertainment of pregnancy status,” they wrote.

Judette Louis, MD, MPH, associate professor of ob.gyn. and department chair at the University of South Florida, Tampa, said in an interview that the findings in these studies were fairly expected, but it’s important to have data from such a large cohort as the one presented at SMFM.

“It confirmed that those who had severe disease were more likely to have chronic medical conditions, mirroring what we saw in the general population who isn’t pregnant,” Dr. Louis said. “I thought this was very crucial because as pregnant women are trying to decide whether they should get the COVID vaccine, this provides support to say that if you’re pregnant, you’re more likely to have severe disease [if you have] other chronic medical conditions.”

The findings also confirm the importance of pregnant people taking precautions to avoid infection.

“Even though these individuals are, as a group, in an age cohort that mostly has asymptomatic disease, for some of them, it results in severe disease and even maternal death,” she said. “They should still take it seriously if they’re pregnant.”

The SMFM abstract study was funded by the NICHD. The Washington study was funded by the University of Washington Population Health Initiative, the National Institutes of Health, and philanthropic gift funds. One coauthor of the Washington study is on a Pfizer and GlaxoSmithKline advisory board for immunizations. No other authors or individuals interviewed reported any disclosures.

Because of significant reduction in delivery of recommended childhood immunization during the pandemic, there is a risk for resurgence of vaccine preventable infections, including measles, pertussis, and polio, which can result in significant morbidity and mortality in children, reported Amy G. Feldman, MD, of Children’s Hospital Colorado, Aurora, and associates.

Yangna/Thinkstock

Will loss of herd immunity lead to vaccine deserts?

When asked to comment, pediatric infectious disease specialist Christopher J. Harrison, MD, said, “My concern is that we may see expansion of what I call ‘vaccine deserts.’ Vaccine deserts occur in underserved communities, areas with pockets of vaccine-hesitant families or among selected groups with difficult access to health care. These vaccine deserts have held a higher density of vulnerables due to low vaccine uptake, often giving rise to outbreaks of vaccine-preventable diseases, e.g., measles, mumps, pertussis. They are usually due to an index case arriving from another vaccine desert (a developing country or a developed country, U.S. or foreign) where the disease is still endemic or pockets of vaccine hesitancy/refusal exist. When detected, local outbreaks result in rapid responses from public/private health collaborations that limit the outbreak. But what if vaccine deserts became more generalized in the U.S. because of loss of vaccine-induced herd immunity in many more or larger areas of our communities because of pandemic-driven lack of vaccinations? That pandemic-driven indirect damage would further stress the health care system and the economy. And it may first show up in the older children whose vaccines were deferred in the first 4-6 months of the pandemic.”

Dr. Feldman and associates cited findings from a collaborative survey conducted by UNICEF, the World Health Organization, Gavi the Vaccine Alliance, the CDC, the Sabin Vaccine Institute, and the Johns Hopkins Bloomberg School of Public Health, which found that immunization programs experienced moderate to severe disruptions or terminations in at least 68 of 129 low and middle-income countries surveyed. According to the WHO, CDC, Red Cross, and GAVI, 94 million people presently are estimated to be at risk as a consequence of not receiving their measles vaccines following the suspensions.

“These national and international declines in routine immunizations have placed the global community at significant risk for outbreaks of vaccine-preventable infections (VPIs) including measles, polio, and pertussis, diseases which are more deadly, more contagious and have a higher reproductive factor (R0) amongst children than COVID-19,” the authors observed.

Dr. Feldman and associates outlined the horrible devastation that these VPI can cause in children, including significantly higher morbidity and mortality than adults, especially among those with immunodeficiencies. Neurologic deficits, paralysis, intellectual disabilities, and vision and hearing loss are just some of the permanent effects conveyed. “It is concerning to imagine how measles could spread across the United States when social distancing restriction[s] are relaxed and unvaccinated children return to school and usual community engagement,” they noted.
 

Collaborative engagement key to course correction

The authors found that primary care providers and public health communities are working not only to restore vaccine administration but also to restore confidence that vaccine delivery is safe in spite of COVID. In addition to recommending specific risk mitigation strategies for clinicians, they also suggested individual practitioners use electronic health records to identify patients with COVID-related lapses in vaccination, employ electronic health record–based parent notification of overdue immunizations, and offer distance-friendly vaccination options that include parking lot or drive-up window vaccine delivery.

Additionally, Dr. Feldman and colleagues recommended that local, state, regional, and national health systems use public service announcements via television and digital as well as social media platforms to convey important messages about the considerable health risks associated with vaccine avoidance and the availability of free or reduced-cost vaccination programs through the federally funded Vaccines For Children program for parents out of work or without insurance. Equally important is messaging around encouraging vaccine opportunities during all health care visits, whether they be subspecialty, urgent care, emergency room, or inpatient visits. In areas where access to clinics is limited, they urged the use of mobile clinics as well as additional focus on providing medical homes to children with poor access to care.

“A partial but expanding safety net may be developing spontaneously, i.e., practices and clinics based on a patient-centered medical home (PCMH) model,” noted Dr. Harrison, professor of pediatrics, University of Missouri-Kansas City, in an interview. “When lagging vaccinations were reported in mid-2020, we checked with a local hospital–based urban clinic and two suburban private practices modeled on PCMH. Each had noted a drastic drop in well checks in the first months of the pandemic. But with ill visits nearly nonexistent, they doubled down on maintaining health maintenance visits. Even though staff and provider work hours were limited, and families were less enthusiastic about well checks, momentum appears to have grown so that, by later in 2020, vaccine uptake rates were again comparable to 2019. So, some already seem to have answered the call, but practices/clinics remain hampered by months of reduced revenue needed to support staff, providers, PPE supplies, and added infection control needs,” he said.The study was funded by the Agency for Healthcare Research Quality. Dr. Isakov disclosed relationships with various pharmaceutical companies outside the submitted work. The other authors had no relevant disclosures. Dr. Harrison’s institution receives grant funding from GSK, Merck, and Pfizer for pediatric vaccine trials and pneumococcal seroprevalence studies on which he is an investigator.

pdnews@mdedge.com

Because of significant reduction in delivery of recommended childhood immunization during the pandemic, there is a risk for resurgence of vaccine preventable infections, including measles, pertussis, and polio, which can result in significant morbidity and mortality in children, reported Amy G. Feldman, MD, of Children’s Hospital Colorado, Aurora, and associates.

Yangna/Thinkstock

Will loss of herd immunity lead to vaccine deserts?

When asked to comment, pediatric infectious disease specialist Christopher J. Harrison, MD, said, “My concern is that we may see expansion of what I call ‘vaccine deserts.’ Vaccine deserts occur in underserved communities, areas with pockets of vaccine-hesitant families or among selected groups with difficult access to health care. These vaccine deserts have held a higher density of vulnerables due to low vaccine uptake, often giving rise to outbreaks of vaccine-preventable diseases, e.g., measles, mumps, pertussis. They are usually due to an index case arriving from another vaccine desert (a developing country or a developed country, U.S. or foreign) where the disease is still endemic or pockets of vaccine hesitancy/refusal exist. When detected, local outbreaks result in rapid responses from public/private health collaborations that limit the outbreak. But what if vaccine deserts became more generalized in the U.S. because of loss of vaccine-induced herd immunity in many more or larger areas of our communities because of pandemic-driven lack of vaccinations? That pandemic-driven indirect damage would further stress the health care system and the economy. And it may first show up in the older children whose vaccines were deferred in the first 4-6 months of the pandemic.”

Dr. Feldman and associates cited findings from a collaborative survey conducted by UNICEF, the World Health Organization, Gavi the Vaccine Alliance, the CDC, the Sabin Vaccine Institute, and the Johns Hopkins Bloomberg School of Public Health, which found that immunization programs experienced moderate to severe disruptions or terminations in at least 68 of 129 low and middle-income countries surveyed. According to the WHO, CDC, Red Cross, and GAVI, 94 million people presently are estimated to be at risk as a consequence of not receiving their measles vaccines following the suspensions.

“These national and international declines in routine immunizations have placed the global community at significant risk for outbreaks of vaccine-preventable infections (VPIs) including measles, polio, and pertussis, diseases which are more deadly, more contagious and have a higher reproductive factor (R0) amongst children than COVID-19,” the authors observed.

Dr. Feldman and associates outlined the horrible devastation that these VPI can cause in children, including significantly higher morbidity and mortality than adults, especially among those with immunodeficiencies. Neurologic deficits, paralysis, intellectual disabilities, and vision and hearing loss are just some of the permanent effects conveyed. “It is concerning to imagine how measles could spread across the United States when social distancing restriction[s] are relaxed and unvaccinated children return to school and usual community engagement,” they noted.
 

Collaborative engagement key to course correction

The authors found that primary care providers and public health communities are working not only to restore vaccine administration but also to restore confidence that vaccine delivery is safe in spite of COVID. In addition to recommending specific risk mitigation strategies for clinicians, they also suggested individual practitioners use electronic health records to identify patients with COVID-related lapses in vaccination, employ electronic health record–based parent notification of overdue immunizations, and offer distance-friendly vaccination options that include parking lot or drive-up window vaccine delivery.

Additionally, Dr. Feldman and colleagues recommended that local, state, regional, and national health systems use public service announcements via television and digital as well as social media platforms to convey important messages about the considerable health risks associated with vaccine avoidance and the availability of free or reduced-cost vaccination programs through the federally funded Vaccines For Children program for parents out of work or without insurance. Equally important is messaging around encouraging vaccine opportunities during all health care visits, whether they be subspecialty, urgent care, emergency room, or inpatient visits. In areas where access to clinics is limited, they urged the use of mobile clinics as well as additional focus on providing medical homes to children with poor access to care.

“A partial but expanding safety net may be developing spontaneously, i.e., practices and clinics based on a patient-centered medical home (PCMH) model,” noted Dr. Harrison, professor of pediatrics, University of Missouri-Kansas City, in an interview. “When lagging vaccinations were reported in mid-2020, we checked with a local hospital–based urban clinic and two suburban private practices modeled on PCMH. Each had noted a drastic drop in well checks in the first months of the pandemic. But with ill visits nearly nonexistent, they doubled down on maintaining health maintenance visits. Even though staff and provider work hours were limited, and families were less enthusiastic about well checks, momentum appears to have grown so that, by later in 2020, vaccine uptake rates were again comparable to 2019. So, some already seem to have answered the call, but practices/clinics remain hampered by months of reduced revenue needed to support staff, providers, PPE supplies, and added infection control needs,” he said.The study was funded by the Agency for Healthcare Research Quality. Dr. Isakov disclosed relationships with various pharmaceutical companies outside the submitted work. The other authors had no relevant disclosures. Dr. Harrison’s institution receives grant funding from GSK, Merck, and Pfizer for pediatric vaccine trials and pneumococcal seroprevalence studies on which he is an investigator.

pdnews@mdedge.com

Because of significant reduction in delivery of recommended childhood immunization during the pandemic, there is a risk for resurgence of vaccine preventable infections, including measles, pertussis, and polio, which can result in significant morbidity and mortality in children, reported Amy G. Feldman, MD, of Children’s Hospital Colorado, Aurora, and associates.

Yangna/Thinkstock

Will loss of herd immunity lead to vaccine deserts?

When asked to comment, pediatric infectious disease specialist Christopher J. Harrison, MD, said, “My concern is that we may see expansion of what I call ‘vaccine deserts.’ Vaccine deserts occur in underserved communities, areas with pockets of vaccine-hesitant families or among selected groups with difficult access to health care. These vaccine deserts have held a higher density of vulnerables due to low vaccine uptake, often giving rise to outbreaks of vaccine-preventable diseases, e.g., measles, mumps, pertussis. They are usually due to an index case arriving from another vaccine desert (a developing country or a developed country, U.S. or foreign) where the disease is still endemic or pockets of vaccine hesitancy/refusal exist. When detected, local outbreaks result in rapid responses from public/private health collaborations that limit the outbreak. But what if vaccine deserts became more generalized in the U.S. because of loss of vaccine-induced herd immunity in many more or larger areas of our communities because of pandemic-driven lack of vaccinations? That pandemic-driven indirect damage would further stress the health care system and the economy. And it may first show up in the older children whose vaccines were deferred in the first 4-6 months of the pandemic.”

Dr. Feldman and associates cited findings from a collaborative survey conducted by UNICEF, the World Health Organization, Gavi the Vaccine Alliance, the CDC, the Sabin Vaccine Institute, and the Johns Hopkins Bloomberg School of Public Health, which found that immunization programs experienced moderate to severe disruptions or terminations in at least 68 of 129 low and middle-income countries surveyed. According to the WHO, CDC, Red Cross, and GAVI, 94 million people presently are estimated to be at risk as a consequence of not receiving their measles vaccines following the suspensions.

“These national and international declines in routine immunizations have placed the global community at significant risk for outbreaks of vaccine-preventable infections (VPIs) including measles, polio, and pertussis, diseases which are more deadly, more contagious and have a higher reproductive factor (R0) amongst children than COVID-19,” the authors observed.

Dr. Feldman and associates outlined the horrible devastation that these VPI can cause in children, including significantly higher morbidity and mortality than adults, especially among those with immunodeficiencies. Neurologic deficits, paralysis, intellectual disabilities, and vision and hearing loss are just some of the permanent effects conveyed. “It is concerning to imagine how measles could spread across the United States when social distancing restriction[s] are relaxed and unvaccinated children return to school and usual community engagement,” they noted.
 

Collaborative engagement key to course correction

The authors found that primary care providers and public health communities are working not only to restore vaccine administration but also to restore confidence that vaccine delivery is safe in spite of COVID. In addition to recommending specific risk mitigation strategies for clinicians, they also suggested individual practitioners use electronic health records to identify patients with COVID-related lapses in vaccination, employ electronic health record–based parent notification of overdue immunizations, and offer distance-friendly vaccination options that include parking lot or drive-up window vaccine delivery.

Additionally, Dr. Feldman and colleagues recommended that local, state, regional, and national health systems use public service announcements via television and digital as well as social media platforms to convey important messages about the considerable health risks associated with vaccine avoidance and the availability of free or reduced-cost vaccination programs through the federally funded Vaccines For Children program for parents out of work or without insurance. Equally important is messaging around encouraging vaccine opportunities during all health care visits, whether they be subspecialty, urgent care, emergency room, or inpatient visits. In areas where access to clinics is limited, they urged the use of mobile clinics as well as additional focus on providing medical homes to children with poor access to care.

“A partial but expanding safety net may be developing spontaneously, i.e., practices and clinics based on a patient-centered medical home (PCMH) model,” noted Dr. Harrison, professor of pediatrics, University of Missouri-Kansas City, in an interview. “When lagging vaccinations were reported in mid-2020, we checked with a local hospital–based urban clinic and two suburban private practices modeled on PCMH. Each had noted a drastic drop in well checks in the first months of the pandemic. But with ill visits nearly nonexistent, they doubled down on maintaining health maintenance visits. Even though staff and provider work hours were limited, and families were less enthusiastic about well checks, momentum appears to have grown so that, by later in 2020, vaccine uptake rates were again comparable to 2019. So, some already seem to have answered the call, but practices/clinics remain hampered by months of reduced revenue needed to support staff, providers, PPE supplies, and added infection control needs,” he said.The study was funded by the Agency for Healthcare Research Quality. Dr. Isakov disclosed relationships with various pharmaceutical companies outside the submitted work. The other authors had no relevant disclosures. Dr. Harrison’s institution receives grant funding from GSK, Merck, and Pfizer for pediatric vaccine trials and pneumococcal seroprevalence studies on which he is an investigator.

pdnews@mdedge.com

Liposomal doxorubicin (Dox) plus pomalidomide (Pom) was safe and active in heavily pretreated patients with Kaposi sarcoma, according to results from a phase 1/2 trial.

“The results of our phase 1/2 study suggest pomalidomide and liposomal doxorubicin is safe with evidence of activity among patients with Kaposi sarcoma,” said investigator Ramya Ramaswami, MBBS, MPH, of the HIV & AIDS malignancy branch at the National Cancer Institute. The results were presented at the Conference on Retroviruses and Opportunistic Infections.

The researchers evaluated the safety and tolerability of Pom/Dox in two groups of patients with Kaposi sarcoma: group 1 included patients with Kaposi sarcoma alone and group 2 included patients with Kaposi sarcoma–associated herpesvirus and concurrent multicentric Castleman disease (KSHV-MCD) and KSHV inflammatory cytokine syndrome (KICS).

“Kaposi sarcoma can be challenging to treat when it co-occurs with KSHV-MCD or KICS, resulting in high mortality rates,” Dr. Ramaswami explained.

Study participants received IV liposomal Dox at 20 mg/m² on day 1 of a 28-day cycle, in addition to oral Pom once daily on days 1-21 at three escalating dose levels (2 mg, 3 mg, or 4 mg, respectively) using a standard 3 + 3 design until plateau of response, progression, dose-limiting toxicities (DLTs) or patient preference. Some eligibility criteria differed between groups 1 and 2. Participants in group 1 were required to be on antiretroviral therapy for at least 1 month and had a performance status of 2 or less, while those in group 2 had a performance status of 3 or less and could be antiretroviral therapy naive.

All participants received oral aspirin thromboprophylaxis (81 mg daily) and could have received prior Kaposi sarcoma therapy.

With respect to outcomes, Kaposi sarcoma responses were assessed using the modified AIDS Clinical Trial Group criteria and KICS and KSHV-MCD responses were evaluated using an NCI clinical benefit criteria.
 

Results

Overall, 34 cisgender men were enrolled in the study: 21 (62%) in group 1 and 13 (38%) in group 2. All participants had severe (T1) Kaposi sarcoma; 32 (94%) participants were HIV-infected and 22 (65%) had prior chemotherapy for Kaposi sarcoma.

While the HIV viral load was largely controlled in both groups, the CD4 count differed, with median CD4 counts of 286 and 92 cells/mcL in groups 1 and 2, respectively.

With respect to safety, no DLTs were observed in group 1. As a result, 12 participants were treated at the maximum tolerated dose (MTD) of 4 mg of Pom. However, two DLTs (grade 3 rash and pharyngeal edema) were observed in group 2 at the 3 mg dose level.

A median of six cycles were administered for all participants and the most common grade 3/4 toxicity was neutropenia; nine patients with grade 3 neutropenia required dose reduction and three patients had febrile neutropenia requiring hospitalization. Other Pom-related adverse events were rash, constipation, and fatigue.

Among evaluable participants receiving two or more cycles, 17 (81%) patients in group 1 had a response (95% confidence interval, 58-95%; 16 partial response and 1 complete response) and 5 (50%) patients in group 2 had a response (95% CI, 19-81%; 4 PR and 1 CR).

“Our waterfall plots indicated that the vast majority of patients in group 1 had a positive change in nodular lesions at baseline,” Dr. Ramaswami said. “Participants in group 2 showed some decrease in nodular lesions, but this was usually temporary.”

Among seven participants with KICS responses, four participants (57%) experienced a CR or PR in symptoms and lab abnormalities associated with KICS; three of six participants (50%) with KSHV-MCD responses experienced a PR as per response criteria.

“While activity was noted, the combination was less well tolerated in patients with Kaposi sarcoma and concurrent KSHV-MCD or KICS,” Dr. Ramaswami said.

During a live discussion, Ronald T. Mitsuyasu, MD, of the University of California, Los Angeles, asked Dr. Ramaswami about the use of liposomal doxorubicin alone in patients with Kaposi sarcoma and concurrent KSHV-MCD or KICS.

While there is currently no data on the use of doxorubicin alone in this population, Dr. Ramaswami noted that she was more confident administering Pom/Dox combination therapy for these patients.

Dr. Ramaswami disclosed financial relationships with the National Cancer Institute, Celgene/Bristol-Myers Squibb, EMD Serono, Merck, CTI Biopharma, and Janssen. The study was funded by a cooperative research and drug development agreement between the National Cancer Institute and Celgene/BMS, EMD Serono, Merck, CTI Biopharma, and Janssen.

Liposomal doxorubicin (Dox) plus pomalidomide (Pom) was safe and active in heavily pretreated patients with Kaposi sarcoma, according to results from a phase 1/2 trial.

“The results of our phase 1/2 study suggest pomalidomide and liposomal doxorubicin is safe with evidence of activity among patients with Kaposi sarcoma,” said investigator Ramya Ramaswami, MBBS, MPH, of the HIV & AIDS malignancy branch at the National Cancer Institute. The results were presented at the Conference on Retroviruses and Opportunistic Infections.

The researchers evaluated the safety and tolerability of Pom/Dox in two groups of patients with Kaposi sarcoma: group 1 included patients with Kaposi sarcoma alone and group 2 included patients with Kaposi sarcoma–associated herpesvirus and concurrent multicentric Castleman disease (KSHV-MCD) and KSHV inflammatory cytokine syndrome (KICS).

“Kaposi sarcoma can be challenging to treat when it co-occurs with KSHV-MCD or KICS, resulting in high mortality rates,” Dr. Ramaswami explained.

Study participants received IV liposomal Dox at 20 mg/m² on day 1 of a 28-day cycle, in addition to oral Pom once daily on days 1-21 at three escalating dose levels (2 mg, 3 mg, or 4 mg, respectively) using a standard 3 + 3 design until plateau of response, progression, dose-limiting toxicities (DLTs) or patient preference. Some eligibility criteria differed between groups 1 and 2. Participants in group 1 were required to be on antiretroviral therapy for at least 1 month and had a performance status of 2 or less, while those in group 2 had a performance status of 3 or less and could be antiretroviral therapy naive.

All participants received oral aspirin thromboprophylaxis (81 mg daily) and could have received prior Kaposi sarcoma therapy.

With respect to outcomes, Kaposi sarcoma responses were assessed using the modified AIDS Clinical Trial Group criteria and KICS and KSHV-MCD responses were evaluated using an NCI clinical benefit criteria.
 

Results

Overall, 34 cisgender men were enrolled in the study: 21 (62%) in group 1 and 13 (38%) in group 2. All participants had severe (T1) Kaposi sarcoma; 32 (94%) participants were HIV-infected and 22 (65%) had prior chemotherapy for Kaposi sarcoma.

While the HIV viral load was largely controlled in both groups, the CD4 count differed, with median CD4 counts of 286 and 92 cells/mcL in groups 1 and 2, respectively.

With respect to safety, no DLTs were observed in group 1. As a result, 12 participants were treated at the maximum tolerated dose (MTD) of 4 mg of Pom. However, two DLTs (grade 3 rash and pharyngeal edema) were observed in group 2 at the 3 mg dose level.

A median of six cycles were administered for all participants and the most common grade 3/4 toxicity was neutropenia; nine patients with grade 3 neutropenia required dose reduction and three patients had febrile neutropenia requiring hospitalization. Other Pom-related adverse events were rash, constipation, and fatigue.

Among evaluable participants receiving two or more cycles, 17 (81%) patients in group 1 had a response (95% confidence interval, 58-95%; 16 partial response and 1 complete response) and 5 (50%) patients in group 2 had a response (95% CI, 19-81%; 4 PR and 1 CR).

“Our waterfall plots indicated that the vast majority of patients in group 1 had a positive change in nodular lesions at baseline,” Dr. Ramaswami said. “Participants in group 2 showed some decrease in nodular lesions, but this was usually temporary.”

Among seven participants with KICS responses, four participants (57%) experienced a CR or PR in symptoms and lab abnormalities associated with KICS; three of six participants (50%) with KSHV-MCD responses experienced a PR as per response criteria.

“While activity was noted, the combination was less well tolerated in patients with Kaposi sarcoma and concurrent KSHV-MCD or KICS,” Dr. Ramaswami said.

During a live discussion, Ronald T. Mitsuyasu, MD, of the University of California, Los Angeles, asked Dr. Ramaswami about the use of liposomal doxorubicin alone in patients with Kaposi sarcoma and concurrent KSHV-MCD or KICS.

While there is currently no data on the use of doxorubicin alone in this population, Dr. Ramaswami noted that she was more confident administering Pom/Dox combination therapy for these patients.

Dr. Ramaswami disclosed financial relationships with the National Cancer Institute, Celgene/Bristol-Myers Squibb, EMD Serono, Merck, CTI Biopharma, and Janssen. The study was funded by a cooperative research and drug development agreement between the National Cancer Institute and Celgene/BMS, EMD Serono, Merck, CTI Biopharma, and Janssen.

Liposomal doxorubicin (Dox) plus pomalidomide (Pom) was safe and active in heavily pretreated patients with Kaposi sarcoma, according to results from a phase 1/2 trial.

“The results of our phase 1/2 study suggest pomalidomide and liposomal doxorubicin is safe with evidence of activity among patients with Kaposi sarcoma,” said investigator Ramya Ramaswami, MBBS, MPH, of the HIV & AIDS malignancy branch at the National Cancer Institute. The results were presented at the Conference on Retroviruses and Opportunistic Infections.

The researchers evaluated the safety and tolerability of Pom/Dox in two groups of patients with Kaposi sarcoma: group 1 included patients with Kaposi sarcoma alone and group 2 included patients with Kaposi sarcoma–associated herpesvirus and concurrent multicentric Castleman disease (KSHV-MCD) and KSHV inflammatory cytokine syndrome (KICS).

“Kaposi sarcoma can be challenging to treat when it co-occurs with KSHV-MCD or KICS, resulting in high mortality rates,” Dr. Ramaswami explained.

Study participants received IV liposomal Dox at 20 mg/m² on day 1 of a 28-day cycle, in addition to oral Pom once daily on days 1-21 at three escalating dose levels (2 mg, 3 mg, or 4 mg, respectively) using a standard 3 + 3 design until plateau of response, progression, dose-limiting toxicities (DLTs) or patient preference. Some eligibility criteria differed between groups 1 and 2. Participants in group 1 were required to be on antiretroviral therapy for at least 1 month and had a performance status of 2 or less, while those in group 2 had a performance status of 3 or less and could be antiretroviral therapy naive.

All participants received oral aspirin thromboprophylaxis (81 mg daily) and could have received prior Kaposi sarcoma therapy.

With respect to outcomes, Kaposi sarcoma responses were assessed using the modified AIDS Clinical Trial Group criteria and KICS and KSHV-MCD responses were evaluated using an NCI clinical benefit criteria.
 

Results

Overall, 34 cisgender men were enrolled in the study: 21 (62%) in group 1 and 13 (38%) in group 2. All participants had severe (T1) Kaposi sarcoma; 32 (94%) participants were HIV-infected and 22 (65%) had prior chemotherapy for Kaposi sarcoma.

While the HIV viral load was largely controlled in both groups, the CD4 count differed, with median CD4 counts of 286 and 92 cells/mcL in groups 1 and 2, respectively.

With respect to safety, no DLTs were observed in group 1. As a result, 12 participants were treated at the maximum tolerated dose (MTD) of 4 mg of Pom. However, two DLTs (grade 3 rash and pharyngeal edema) were observed in group 2 at the 3 mg dose level.

A median of six cycles were administered for all participants and the most common grade 3/4 toxicity was neutropenia; nine patients with grade 3 neutropenia required dose reduction and three patients had febrile neutropenia requiring hospitalization. Other Pom-related adverse events were rash, constipation, and fatigue.

Among evaluable participants receiving two or more cycles, 17 (81%) patients in group 1 had a response (95% confidence interval, 58-95%; 16 partial response and 1 complete response) and 5 (50%) patients in group 2 had a response (95% CI, 19-81%; 4 PR and 1 CR).

“Our waterfall plots indicated that the vast majority of patients in group 1 had a positive change in nodular lesions at baseline,” Dr. Ramaswami said. “Participants in group 2 showed some decrease in nodular lesions, but this was usually temporary.”

Among seven participants with KICS responses, four participants (57%) experienced a CR or PR in symptoms and lab abnormalities associated with KICS; three of six participants (50%) with KSHV-MCD responses experienced a PR as per response criteria.

“While activity was noted, the combination was less well tolerated in patients with Kaposi sarcoma and concurrent KSHV-MCD or KICS,” Dr. Ramaswami said.

During a live discussion, Ronald T. Mitsuyasu, MD, of the University of California, Los Angeles, asked Dr. Ramaswami about the use of liposomal doxorubicin alone in patients with Kaposi sarcoma and concurrent KSHV-MCD or KICS.

While there is currently no data on the use of doxorubicin alone in this population, Dr. Ramaswami noted that she was more confident administering Pom/Dox combination therapy for these patients.

Dr. Ramaswami disclosed financial relationships with the National Cancer Institute, Celgene/Bristol-Myers Squibb, EMD Serono, Merck, CTI Biopharma, and Janssen. The study was funded by a cooperative research and drug development agreement between the National Cancer Institute and Celgene/BMS, EMD Serono, Merck, CTI Biopharma, and Janssen.

Elevated vaginal pH at the time of cervical intraepithelial neoplasia 2 diagnosis may be a useful marker of CIN 2 persistence/progression, as well as the rate of persistence/progression in HIV-positive women, new research suggests.

“We analyzed data from the Women’s Interagency HIV Study [WIHS], an observational, longitudinal cohort of women with and without HIV to determine factors that may influence CIN 2 natural history,” said Kate Michel, PhD, MPH, of Georgetown University, Washington. She presented the results at the Conference on Retroviruses and Opportunistic Infections.

As previous data have shown a high incidence of CIN 2 progression among women with HIV, the researchers evaluated the role of human papillomavirus (HPV) type, local immune response, and markers of the cervicovaginal microbiome on the risk of CIN 2 persistence/progression.

Within the cohort, follow-up visits occur every 6 months, and clinical data is collected via questionnaires, physical and gynecologic exams, and biological samples. As no specific treatment is offered in the WIHS, treatment for cervical abnormalities is abstracted from medical records.

In the present study, Dr. Michel and colleagues selected up to four banked cervicovaginal lavage (CVL) samples per woman, with the first sample selected 6-12 months prior to CIN 2 diagnosis, the second at CIN 2 diagnosis, the third between CIN 2 diagnosis and outcome, and the fourth at the outcome visit.

The investigators performed HPV typing and muiltiplex immune mediator testing on each CVL sample. Lab results from WIHS core testing were also extracted, including plasma CD4+ T-cell count and HIV viral load, as well as vaginal pH and Nugent’s score.

Study outcomes included persistence/progression and regression, defined as a subsequent CIN 2 or CIN 3 diagnosis and subsequent CIN 1 or normal diagnosis, respectively. Logistic regression models were used to determine CIN 2 regression versus persistence/progression.
 

Results

A total of 337 samples were obtained and 94 women were included in the analysis. Key demographic and behavioral factor were similar at CIN 2 diagnosis.

The majority of participants were African American (53.2%) and on antiretroviral therapy (66.0%). The most prevalent high-risk types were HPV-58 (18.4%) and HPV-16 (17.5%).

After a median 12.5 years of follow-up, 33 participants (35.1%) with incident CIN 2 had a subsequent CIN 2/CIN 3 diagnosis and those who regressed had a higher CD4 T-cell count at CIN 2 diagnosis (P = .02).

Each subsequent high-risk HPV type identified at the pre–CIN 2 visit was associated with higher odds of CIN2 persistence/progression (odds ratio, 2.27; 95% confidence interval, 1.15-4.50).

Bacterial vaginosis (adjusted OR, 5.08; 95% CI, 1.30-19.94) and vaginal pH (aOR, 2.27; 95% CI, 1.15-4.50) at the CIN 2 diagnosis visit were each associated with increased odds of CIN 2 persistence/progression.

Vaginal pH greater than 4.5 at CIN 2 diagnosis was also associated with unadjusted time to CIN 2 persistence/progression (log rank P = .002) and an increased rate of CIN 2 persistence/progression (adjusted hazard ratio, 3.37; 95% CI, 1.26-8.99).

Furthermore, among participants who did not receive CIN 2 treatment, vaginal pH remained associated with greater odds of CIN 2 persistence/progression (OR, 2.46; 95% CI, 1.19-5.13). Cervicovaginal immune mediator levels were not associated with CIN 2 persistence/progression.

“The most striking finding from this work was that vaginal pH was associated with higher odds of, quicker time to, and increased hazard of CIN 2 persistence/progression,” Dr. Michel said. “We postulate this effect is mediated by the cervical microbiome, but more work is needed to establish the exact mechanism.”

“It would be interesting to test whether this association might be explained by different vaginal cleaning techniques, such as douching,” said moderator Ronald T. Mitsuyasu, MD, of the University of California, Los Angeles.

“We’re currently working on an analysis of cervicovaginal bacterial species to explore the microbiome in more detail,” Dr. Michel concluded.

Dr. Michel disclosed no conflicts of interest. The study was supported by multiple sources, including the National Institute of Allergy and Infectious Diseases, the National Cancer Institute, and the Georgetown-Howard Universities Center for Clinical and Translational Science.

Elevated vaginal pH at the time of cervical intraepithelial neoplasia 2 diagnosis may be a useful marker of CIN 2 persistence/progression, as well as the rate of persistence/progression in HIV-positive women, new research suggests.

“We analyzed data from the Women’s Interagency HIV Study [WIHS], an observational, longitudinal cohort of women with and without HIV to determine factors that may influence CIN 2 natural history,” said Kate Michel, PhD, MPH, of Georgetown University, Washington. She presented the results at the Conference on Retroviruses and Opportunistic Infections.

As previous data have shown a high incidence of CIN 2 progression among women with HIV, the researchers evaluated the role of human papillomavirus (HPV) type, local immune response, and markers of the cervicovaginal microbiome on the risk of CIN 2 persistence/progression.

Within the cohort, follow-up visits occur every 6 months, and clinical data is collected via questionnaires, physical and gynecologic exams, and biological samples. As no specific treatment is offered in the WIHS, treatment for cervical abnormalities is abstracted from medical records.

In the present study, Dr. Michel and colleagues selected up to four banked cervicovaginal lavage (CVL) samples per woman, with the first sample selected 6-12 months prior to CIN 2 diagnosis, the second at CIN 2 diagnosis, the third between CIN 2 diagnosis and outcome, and the fourth at the outcome visit.

The investigators performed HPV typing and muiltiplex immune mediator testing on each CVL sample. Lab results from WIHS core testing were also extracted, including plasma CD4+ T-cell count and HIV viral load, as well as vaginal pH and Nugent’s score.

Study outcomes included persistence/progression and regression, defined as a subsequent CIN 2 or CIN 3 diagnosis and subsequent CIN 1 or normal diagnosis, respectively. Logistic regression models were used to determine CIN 2 regression versus persistence/progression.
 

Results

A total of 337 samples were obtained and 94 women were included in the analysis. Key demographic and behavioral factor were similar at CIN 2 diagnosis.

The majority of participants were African American (53.2%) and on antiretroviral therapy (66.0%). The most prevalent high-risk types were HPV-58 (18.4%) and HPV-16 (17.5%).

After a median 12.5 years of follow-up, 33 participants (35.1%) with incident CIN 2 had a subsequent CIN 2/CIN 3 diagnosis and those who regressed had a higher CD4 T-cell count at CIN 2 diagnosis (P = .02).

Each subsequent high-risk HPV type identified at the pre–CIN 2 visit was associated with higher odds of CIN2 persistence/progression (odds ratio, 2.27; 95% confidence interval, 1.15-4.50).

Bacterial vaginosis (adjusted OR, 5.08; 95% CI, 1.30-19.94) and vaginal pH (aOR, 2.27; 95% CI, 1.15-4.50) at the CIN 2 diagnosis visit were each associated with increased odds of CIN 2 persistence/progression.

Vaginal pH greater than 4.5 at CIN 2 diagnosis was also associated with unadjusted time to CIN 2 persistence/progression (log rank P = .002) and an increased rate of CIN 2 persistence/progression (adjusted hazard ratio, 3.37; 95% CI, 1.26-8.99).

Furthermore, among participants who did not receive CIN 2 treatment, vaginal pH remained associated with greater odds of CIN 2 persistence/progression (OR, 2.46; 95% CI, 1.19-5.13). Cervicovaginal immune mediator levels were not associated with CIN 2 persistence/progression.

“The most striking finding from this work was that vaginal pH was associated with higher odds of, quicker time to, and increased hazard of CIN 2 persistence/progression,” Dr. Michel said. “We postulate this effect is mediated by the cervical microbiome, but more work is needed to establish the exact mechanism.”

“It would be interesting to test whether this association might be explained by different vaginal cleaning techniques, such as douching,” said moderator Ronald T. Mitsuyasu, MD, of the University of California, Los Angeles.

“We’re currently working on an analysis of cervicovaginal bacterial species to explore the microbiome in more detail,” Dr. Michel concluded.

Dr. Michel disclosed no conflicts of interest. The study was supported by multiple sources, including the National Institute of Allergy and Infectious Diseases, the National Cancer Institute, and the Georgetown-Howard Universities Center for Clinical and Translational Science.

Elevated vaginal pH at the time of cervical intraepithelial neoplasia 2 diagnosis may be a useful marker of CIN 2 persistence/progression, as well as the rate of persistence/progression in HIV-positive women, new research suggests.

“We analyzed data from the Women’s Interagency HIV Study [WIHS], an observational, longitudinal cohort of women with and without HIV to determine factors that may influence CIN 2 natural history,” said Kate Michel, PhD, MPH, of Georgetown University, Washington. She presented the results at the Conference on Retroviruses and Opportunistic Infections.

As previous data have shown a high incidence of CIN 2 progression among women with HIV, the researchers evaluated the role of human papillomavirus (HPV) type, local immune response, and markers of the cervicovaginal microbiome on the risk of CIN 2 persistence/progression.

Within the cohort, follow-up visits occur every 6 months, and clinical data is collected via questionnaires, physical and gynecologic exams, and biological samples. As no specific treatment is offered in the WIHS, treatment for cervical abnormalities is abstracted from medical records.

In the present study, Dr. Michel and colleagues selected up to four banked cervicovaginal lavage (CVL) samples per woman, with the first sample selected 6-12 months prior to CIN 2 diagnosis, the second at CIN 2 diagnosis, the third between CIN 2 diagnosis and outcome, and the fourth at the outcome visit.

The investigators performed HPV typing and muiltiplex immune mediator testing on each CVL sample. Lab results from WIHS core testing were also extracted, including plasma CD4+ T-cell count and HIV viral load, as well as vaginal pH and Nugent’s score.

Study outcomes included persistence/progression and regression, defined as a subsequent CIN 2 or CIN 3 diagnosis and subsequent CIN 1 or normal diagnosis, respectively. Logistic regression models were used to determine CIN 2 regression versus persistence/progression.
 

Results

A total of 337 samples were obtained and 94 women were included in the analysis. Key demographic and behavioral factor were similar at CIN 2 diagnosis.

The majority of participants were African American (53.2%) and on antiretroviral therapy (66.0%). The most prevalent high-risk types were HPV-58 (18.4%) and HPV-16 (17.5%).

After a median 12.5 years of follow-up, 33 participants (35.1%) with incident CIN 2 had a subsequent CIN 2/CIN 3 diagnosis and those who regressed had a higher CD4 T-cell count at CIN 2 diagnosis (P = .02).

Each subsequent high-risk HPV type identified at the pre–CIN 2 visit was associated with higher odds of CIN2 persistence/progression (odds ratio, 2.27; 95% confidence interval, 1.15-4.50).

Bacterial vaginosis (adjusted OR, 5.08; 95% CI, 1.30-19.94) and vaginal pH (aOR, 2.27; 95% CI, 1.15-4.50) at the CIN 2 diagnosis visit were each associated with increased odds of CIN 2 persistence/progression.

Vaginal pH greater than 4.5 at CIN 2 diagnosis was also associated with unadjusted time to CIN 2 persistence/progression (log rank P = .002) and an increased rate of CIN 2 persistence/progression (adjusted hazard ratio, 3.37; 95% CI, 1.26-8.99).

Furthermore, among participants who did not receive CIN 2 treatment, vaginal pH remained associated with greater odds of CIN 2 persistence/progression (OR, 2.46; 95% CI, 1.19-5.13). Cervicovaginal immune mediator levels were not associated with CIN 2 persistence/progression.

“The most striking finding from this work was that vaginal pH was associated with higher odds of, quicker time to, and increased hazard of CIN 2 persistence/progression,” Dr. Michel said. “We postulate this effect is mediated by the cervical microbiome, but more work is needed to establish the exact mechanism.”

“It would be interesting to test whether this association might be explained by different vaginal cleaning techniques, such as douching,” said moderator Ronald T. Mitsuyasu, MD, of the University of California, Los Angeles.

“We’re currently working on an analysis of cervicovaginal bacterial species to explore the microbiome in more detail,” Dr. Michel concluded.

Dr. Michel disclosed no conflicts of interest. The study was supported by multiple sources, including the National Institute of Allergy and Infectious Diseases, the National Cancer Institute, and the Georgetown-Howard Universities Center for Clinical and Translational Science.

Edward H. Livingston, MD, has resigned as deputy editor of JAMA after he and the journal faced significant backlash over a February 2021 podcast that questioned the existence of structural racism.

JAMA editor in chief Howard Bauchner, MD, apologized to JAMA staff and stakeholders and asked for and received Dr. Livingston’s resignation, according to a statement from AMA CEO James Madara.

More than 2,000 people have signed a petition on Change.org calling for an investigation at JAMA over the podcast, called “Structural Racism for Doctors: What Is It?”

It appears they are now getting their wish. Dr. Bauchner announced that the journal’s oversight committee is investigating how the podcast and a tweet promoting the episode were developed, reviewed, and ultimately posted.

“This investigation and report of its findings will be thorough and completed rapidly,” Dr. Bauchner said.

Dr. Livingston, the host of the podcast, has been heavily criticized across social media. During the podcast, Dr. Livingston, who is White, said: “Structural racism is an unfortunate term. Personally, I think taking racism out of the conversation will help. Many of us are offended by the concept that we are racist.”

The audio of the podcast has been deleted from JAMA’s website. In its place is audio of a statement from Dr. Bauchner. In his statement, which he released last week, he said the comments in the podcast, which also featured Mitch Katz, MD, were “inaccurate, offensive, hurtful, and inconsistent with the standards of JAMA.”

Dr. Katz is an editor at JAMA Internal Medicine and CEO of NYC Health + Hospitals in New York.

Also deleted was a JAMA tweet promoting the podcast episode. The tweet said: “No physician is racist, so how can there be structural racism in health care? An explanation of the idea by doctors for doctors in this user-friendly podcast.”

The incident was met with anger and confusion in the medical community.

Herbert C. Smitherman, MD, vice dean of diversity and community affairs at Wayne State University, Detroit, noted after hearing the podcast that it was a symptom of a much larger problem.

“At its core, this podcast had racist tendencies. Those attitudes are why you don’t have as many articles by Black and Brown people in JAMA,” he said. “People’s attitudes, whether conscious or unconscious, are what drive the policies and practices which create the structural racism.”

Dr. Katz responded to the backlash last week with the following statement: “Systemic racism exists in our country. The disparate effects of the pandemic have made this painfully clear in New York City and across the country.

“As clinicians, we must understand how these structures and policies have a direct impact on the health outcomes of the patients and communities we serve. It is woefully naive to say that no physician is a racist just because the Civil Rights Act of 1964 forbade it, or that we should avoid the term ‘systematic racism’ because it makes people uncomfortable. We must and can do better.”

JAMA, an independent arm of the AMA, is taking other steps to address concerns. Its executive publisher, Thomas Easley, held an employee town hall this week, and said JAMA acknowledges that “structural racism is real, pernicious, and pervasive in health care.” The journal is also starting an “end-to-end review” of all editorial processes across all JAMA publications. Finally, the journal will also create a new associate editor’s position who will provide “insight and counsel” on racism and structural racism in health care.

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

Edward H. Livingston, MD, has resigned as deputy editor of JAMA after he and the journal faced significant backlash over a February 2021 podcast that questioned the existence of structural racism.

JAMA editor in chief Howard Bauchner, MD, apologized to JAMA staff and stakeholders and asked for and received Dr. Livingston’s resignation, according to a statement from AMA CEO James Madara.

More than 2,000 people have signed a petition on Change.org calling for an investigation at JAMA over the podcast, called “Structural Racism for Doctors: What Is It?”

It appears they are now getting their wish. Dr. Bauchner announced that the journal’s oversight committee is investigating how the podcast and a tweet promoting the episode were developed, reviewed, and ultimately posted.

“This investigation and report of its findings will be thorough and completed rapidly,” Dr. Bauchner said.

Dr. Livingston, the host of the podcast, has been heavily criticized across social media. During the podcast, Dr. Livingston, who is White, said: “Structural racism is an unfortunate term. Personally, I think taking racism out of the conversation will help. Many of us are offended by the concept that we are racist.”

The audio of the podcast has been deleted from JAMA’s website. In its place is audio of a statement from Dr. Bauchner. In his statement, which he released last week, he said the comments in the podcast, which also featured Mitch Katz, MD, were “inaccurate, offensive, hurtful, and inconsistent with the standards of JAMA.”

Dr. Katz is an editor at JAMA Internal Medicine and CEO of NYC Health + Hospitals in New York.

Also deleted was a JAMA tweet promoting the podcast episode. The tweet said: “No physician is racist, so how can there be structural racism in health care? An explanation of the idea by doctors for doctors in this user-friendly podcast.”

The incident was met with anger and confusion in the medical community.

Herbert C. Smitherman, MD, vice dean of diversity and community affairs at Wayne State University, Detroit, noted after hearing the podcast that it was a symptom of a much larger problem.

“At its core, this podcast had racist tendencies. Those attitudes are why you don’t have as many articles by Black and Brown people in JAMA,” he said. “People’s attitudes, whether conscious or unconscious, are what drive the policies and practices which create the structural racism.”

Dr. Katz responded to the backlash last week with the following statement: “Systemic racism exists in our country. The disparate effects of the pandemic have made this painfully clear in New York City and across the country.

“As clinicians, we must understand how these structures and policies have a direct impact on the health outcomes of the patients and communities we serve. It is woefully naive to say that no physician is a racist just because the Civil Rights Act of 1964 forbade it, or that we should avoid the term ‘systematic racism’ because it makes people uncomfortable. We must and can do better.”

JAMA, an independent arm of the AMA, is taking other steps to address concerns. Its executive publisher, Thomas Easley, held an employee town hall this week, and said JAMA acknowledges that “structural racism is real, pernicious, and pervasive in health care.” The journal is also starting an “end-to-end review” of all editorial processes across all JAMA publications. Finally, the journal will also create a new associate editor’s position who will provide “insight and counsel” on racism and structural racism in health care.

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

Edward H. Livingston, MD, has resigned as deputy editor of JAMA after he and the journal faced significant backlash over a February 2021 podcast that questioned the existence of structural racism.

JAMA editor in chief Howard Bauchner, MD, apologized to JAMA staff and stakeholders and asked for and received Dr. Livingston’s resignation, according to a statement from AMA CEO James Madara.

More than 2,000 people have signed a petition on Change.org calling for an investigation at JAMA over the podcast, called “Structural Racism for Doctors: What Is It?”

It appears they are now getting their wish. Dr. Bauchner announced that the journal’s oversight committee is investigating how the podcast and a tweet promoting the episode were developed, reviewed, and ultimately posted.

“This investigation and report of its findings will be thorough and completed rapidly,” Dr. Bauchner said.

Dr. Livingston, the host of the podcast, has been heavily criticized across social media. During the podcast, Dr. Livingston, who is White, said: “Structural racism is an unfortunate term. Personally, I think taking racism out of the conversation will help. Many of us are offended by the concept that we are racist.”

The audio of the podcast has been deleted from JAMA’s website. In its place is audio of a statement from Dr. Bauchner. In his statement, which he released last week, he said the comments in the podcast, which also featured Mitch Katz, MD, were “inaccurate, offensive, hurtful, and inconsistent with the standards of JAMA.”

Dr. Katz is an editor at JAMA Internal Medicine and CEO of NYC Health + Hospitals in New York.

Also deleted was a JAMA tweet promoting the podcast episode. The tweet said: “No physician is racist, so how can there be structural racism in health care? An explanation of the idea by doctors for doctors in this user-friendly podcast.”

The incident was met with anger and confusion in the medical community.

Herbert C. Smitherman, MD, vice dean of diversity and community affairs at Wayne State University, Detroit, noted after hearing the podcast that it was a symptom of a much larger problem.

“At its core, this podcast had racist tendencies. Those attitudes are why you don’t have as many articles by Black and Brown people in JAMA,” he said. “People’s attitudes, whether conscious or unconscious, are what drive the policies and practices which create the structural racism.”

Dr. Katz responded to the backlash last week with the following statement: “Systemic racism exists in our country. The disparate effects of the pandemic have made this painfully clear in New York City and across the country.

“As clinicians, we must understand how these structures and policies have a direct impact on the health outcomes of the patients and communities we serve. It is woefully naive to say that no physician is a racist just because the Civil Rights Act of 1964 forbade it, or that we should avoid the term ‘systematic racism’ because it makes people uncomfortable. We must and can do better.”

JAMA, an independent arm of the AMA, is taking other steps to address concerns. Its executive publisher, Thomas Easley, held an employee town hall this week, and said JAMA acknowledges that “structural racism is real, pernicious, and pervasive in health care.” The journal is also starting an “end-to-end review” of all editorial processes across all JAMA publications. Finally, the journal will also create a new associate editor’s position who will provide “insight and counsel” on racism and structural racism in health care.

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

HIV-positive patients who are adherent with antiretroviral medications are achieving undetectable or very low levels of HIV viremia and living longer. In response, clinical care is continually adapting to the dramatically altered natural history of disease.

Today, the cutting edge of clinical care overlaps with primary care. The clinical vanguard addresses the medical vulnerabilities of patients with HIV, seeking to eliminate preventable morbidity and premature death. Among this clinical vanguard is the screening for and prevention of anal cancer. With the increased longevity of people living with HIV and the nearly universal exposure to human papillomavirus (HPV), there is now potential for progression to mucosal cellular dysplasia and eventual malignancy.

We know that prevention is possible because of the example of cervical cancer, the etiology of which is exposure to oncogenic serotypes of HPV (16 and 18 are most common). Screenings for cervical cancer (regular clinical examinations and Pap smears) and treatments to eliminate high-grade dysplasia have decreased the incidence rate by over 50% since the 1970s. Vaccination against HPV has been available since 2006 and offers the prospect of preventing HPV-associated malignancies, including head and neck cancer, in future decades.

However, rates of anal cancer are increasing. The CDC estimates that about 4,700 new cases of HPV-associated anal cancers are diagnosed in women and about 2,300 are diagnosed in men each year in the United States. Anal cancer rates in individuals with HIV have increased in the era of effective antiretrovirals and greater longevity. The highest rates, at 95 per 100,000, are in HIV-positive men who have sex with men. Very similar rates were noted in a more recent study that found increased risk with advancing age and in those with an AIDS diagnosis.
 

All patients with HIV should be screened

The New York State AIDS Institute Clinical Guidelines Program recommends screening for anal dysplasia in all patients with HIV. A proactive approach similar to cervical cancer screening is appropriate and includes measures easily implemented by all clinicians.

• History: Assess for rectal symptoms, anal pain, discharge, and lumps.
• Physical exam: Assess for presence of perianal lesions; perform a thorough digital rectal exam.
• Anal Pap test for anal cytology: Insert a Dacron swab moistened with tap water about 3 inches into the anal canal, applying pressure to lateral anal walls and rotating the swab. Then remove and place the swab into liquid cytology solution, shake vigorously for a full 30 seconds, and assess for any dysplasia (high-grade squamous intraepithelial lesion, low-grade intraepithelial lesion, atypical squamous cells of undetermined significance), which would warrant further evaluation by high-resolution anoscopy (HRA).

High-resolution anoscopy

HRA for anal dysplasia corresponds to colposcopy for cervical dysplasia. The ability to treat and eliminate high-risk precursor lesions interrupts the progression to malignancy. The efficacy of this strategy is being evaluated in a National Institutes of Health prospective trial called the Anchor Study. The epidemiology of HPV; the clinical horror of witnessing the painful, preventable deaths of young patients with well-controlled HIV caused by anal cancer; and the example of controlling cervical cancer have motivated my practice to assure comprehensive care for our patients.

Unfortunately, establishing HRA in one’s practice is challenging. Barriers to practice include the expense of required equipment and the absence of consensus on specific products. In addition, hands-on precepting to ease newcomers to competence is not generally available. Considerable skill is required for complete visualization of the anal transformative zone in the folds of the anal canal, and recognizing high-risk lesions requires study and accumulated experience. The International Anal Neoplasia Society is a useful resource that also offers a training course. We are invited to train ourselves, and to rely on the eventual feedback of biopsy results and the forbearance of our early patients.

The expanding scope of our medical practices must shift to meet the evolving needs of the growing population of virologically suppressed patients who are living longer. HIV care involves curing life-threatening opportunistic infections, encouraging antiretroviral adherence, and providing comprehensive care – which now includes preventing anal cancer.

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

HIV-positive patients who are adherent with antiretroviral medications are achieving undetectable or very low levels of HIV viremia and living longer. In response, clinical care is continually adapting to the dramatically altered natural history of disease.

Today, the cutting edge of clinical care overlaps with primary care. The clinical vanguard addresses the medical vulnerabilities of patients with HIV, seeking to eliminate preventable morbidity and premature death. Among this clinical vanguard is the screening for and prevention of anal cancer. With the increased longevity of people living with HIV and the nearly universal exposure to human papillomavirus (HPV), there is now potential for progression to mucosal cellular dysplasia and eventual malignancy.

We know that prevention is possible because of the example of cervical cancer, the etiology of which is exposure to oncogenic serotypes of HPV (16 and 18 are most common). Screenings for cervical cancer (regular clinical examinations and Pap smears) and treatments to eliminate high-grade dysplasia have decreased the incidence rate by over 50% since the 1970s. Vaccination against HPV has been available since 2006 and offers the prospect of preventing HPV-associated malignancies, including head and neck cancer, in future decades.

However, rates of anal cancer are increasing. The CDC estimates that about 4,700 new cases of HPV-associated anal cancers are diagnosed in women and about 2,300 are diagnosed in men each year in the United States. Anal cancer rates in individuals with HIV have increased in the era of effective antiretrovirals and greater longevity. The highest rates, at 95 per 100,000, are in HIV-positive men who have sex with men. Very similar rates were noted in a more recent study that found increased risk with advancing age and in those with an AIDS diagnosis.
 

All patients with HIV should be screened

The New York State AIDS Institute Clinical Guidelines Program recommends screening for anal dysplasia in all patients with HIV. A proactive approach similar to cervical cancer screening is appropriate and includes measures easily implemented by all clinicians.

• History: Assess for rectal symptoms, anal pain, discharge, and lumps.
• Physical exam: Assess for presence of perianal lesions; perform a thorough digital rectal exam.
• Anal Pap test for anal cytology: Insert a Dacron swab moistened with tap water about 3 inches into the anal canal, applying pressure to lateral anal walls and rotating the swab. Then remove and place the swab into liquid cytology solution, shake vigorously for a full 30 seconds, and assess for any dysplasia (high-grade squamous intraepithelial lesion, low-grade intraepithelial lesion, atypical squamous cells of undetermined significance), which would warrant further evaluation by high-resolution anoscopy (HRA).

High-resolution anoscopy

HRA for anal dysplasia corresponds to colposcopy for cervical dysplasia. The ability to treat and eliminate high-risk precursor lesions interrupts the progression to malignancy. The efficacy of this strategy is being evaluated in a National Institutes of Health prospective trial called the Anchor Study. The epidemiology of HPV; the clinical horror of witnessing the painful, preventable deaths of young patients with well-controlled HIV caused by anal cancer; and the example of controlling cervical cancer have motivated my practice to assure comprehensive care for our patients.

Unfortunately, establishing HRA in one’s practice is challenging. Barriers to practice include the expense of required equipment and the absence of consensus on specific products. In addition, hands-on precepting to ease newcomers to competence is not generally available. Considerable skill is required for complete visualization of the anal transformative zone in the folds of the anal canal, and recognizing high-risk lesions requires study and accumulated experience. The International Anal Neoplasia Society is a useful resource that also offers a training course. We are invited to train ourselves, and to rely on the eventual feedback of biopsy results and the forbearance of our early patients.

The expanding scope of our medical practices must shift to meet the evolving needs of the growing population of virologically suppressed patients who are living longer. HIV care involves curing life-threatening opportunistic infections, encouraging antiretroviral adherence, and providing comprehensive care – which now includes preventing anal cancer.

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

HIV-positive patients who are adherent with antiretroviral medications are achieving undetectable or very low levels of HIV viremia and living longer. In response, clinical care is continually adapting to the dramatically altered natural history of disease.

Today, the cutting edge of clinical care overlaps with primary care. The clinical vanguard addresses the medical vulnerabilities of patients with HIV, seeking to eliminate preventable morbidity and premature death. Among this clinical vanguard is the screening for and prevention of anal cancer. With the increased longevity of people living with HIV and the nearly universal exposure to human papillomavirus (HPV), there is now potential for progression to mucosal cellular dysplasia and eventual malignancy.

We know that prevention is possible because of the example of cervical cancer, the etiology of which is exposure to oncogenic serotypes of HPV (16 and 18 are most common). Screenings for cervical cancer (regular clinical examinations and Pap smears) and treatments to eliminate high-grade dysplasia have decreased the incidence rate by over 50% since the 1970s. Vaccination against HPV has been available since 2006 and offers the prospect of preventing HPV-associated malignancies, including head and neck cancer, in future decades.

However, rates of anal cancer are increasing. The CDC estimates that about 4,700 new cases of HPV-associated anal cancers are diagnosed in women and about 2,300 are diagnosed in men each year in the United States. Anal cancer rates in individuals with HIV have increased in the era of effective antiretrovirals and greater longevity. The highest rates, at 95 per 100,000, are in HIV-positive men who have sex with men. Very similar rates were noted in a more recent study that found increased risk with advancing age and in those with an AIDS diagnosis.
 

All patients with HIV should be screened

The New York State AIDS Institute Clinical Guidelines Program recommends screening for anal dysplasia in all patients with HIV. A proactive approach similar to cervical cancer screening is appropriate and includes measures easily implemented by all clinicians.

• History: Assess for rectal symptoms, anal pain, discharge, and lumps.
• Physical exam: Assess for presence of perianal lesions; perform a thorough digital rectal exam.
• Anal Pap test for anal cytology: Insert a Dacron swab moistened with tap water about 3 inches into the anal canal, applying pressure to lateral anal walls and rotating the swab. Then remove and place the swab into liquid cytology solution, shake vigorously for a full 30 seconds, and assess for any dysplasia (high-grade squamous intraepithelial lesion, low-grade intraepithelial lesion, atypical squamous cells of undetermined significance), which would warrant further evaluation by high-resolution anoscopy (HRA).

High-resolution anoscopy

HRA for anal dysplasia corresponds to colposcopy for cervical dysplasia. The ability to treat and eliminate high-risk precursor lesions interrupts the progression to malignancy. The efficacy of this strategy is being evaluated in a National Institutes of Health prospective trial called the Anchor Study. The epidemiology of HPV; the clinical horror of witnessing the painful, preventable deaths of young patients with well-controlled HIV caused by anal cancer; and the example of controlling cervical cancer have motivated my practice to assure comprehensive care for our patients.

Unfortunately, establishing HRA in one’s practice is challenging. Barriers to practice include the expense of required equipment and the absence of consensus on specific products. In addition, hands-on precepting to ease newcomers to competence is not generally available. Considerable skill is required for complete visualization of the anal transformative zone in the folds of the anal canal, and recognizing high-risk lesions requires study and accumulated experience. The International Anal Neoplasia Society is a useful resource that also offers a training course. We are invited to train ourselves, and to rely on the eventual feedback of biopsy results and the forbearance of our early patients.

The expanding scope of our medical practices must shift to meet the evolving needs of the growing population of virologically suppressed patients who are living longer. HIV care involves curing life-threatening opportunistic infections, encouraging antiretroviral adherence, and providing comprehensive care – which now includes preventing anal cancer.

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

Both high and low serum sodium levels are associated with adverse outcomes for hospitalized patients with COVID-19, new research suggests.

In the retrospective study of 488 patients hospitalized with COVID-19 at one of two London hospitals between February and May 2020, hypernatremia (defined as serum sodium level >145 mmol/L) at any time point during hospital stay was associated with a threefold increase in inpatient mortality.

Hyponatremia (serum sodium level <135 mmol/L) was associated with twice the likelihood of requiring advanced ventilatory support. In-hospital mortality was also increased among patients with hypovolemic hyponatremia.

“Serum sodium values could be used in clinical practice to identify patients with COVID-19 at high risk of poor outcomes who would benefit from more intensive monitoring and judicious rehydration,” Ploutarchos Tzoulis, MD, PhD, and colleagues wrote in their article, which was published online on Feb. 24, 2021, in the Journal of Clinical Endocrinology and Metabolism.

The findings will be presented at the upcoming news conference held by the Endocrine Society
 

Should sodium be included in a risk calculator for COVID-19?

Dr. Tzoulis, professor of endocrinology at the University College London Medical School, said in an interview that “sodium could be incorporated in risk calculators across other routine biomarkers, such as white cell count, lymphocytes, and CRP [C-reactive protein], in order to provide a tool for dynamic risk stratification throughout the clinical course of COVID-19 and assist clinical decision-making.”

Moreover, he said, “we should follow less conservative strategies in the rate and amount of fluid resuscitation in order to prevent hypernatremia, which is induced by negative fluid balance and can often be iatrogenic.”

Asked to comment, Steven Q. Simpson, MD, professor of medicine in the division of pulmonary, critical care, and sleep medicine at the University of Kansas, Kansas City, said that the article is missing key results that would assist in interpreting of the findings.

“Data regarding diuretic use and sparing of fluid administration are not in the paper. ... It is simply not possible to tell whether serum sodium is a ‘predictor’ ... or if it is a side effect of other issues or actions taken by physicians in patients who are progressing poorly.

“To say that sodium needs to be included in a risk calculator is to subtly suggest that there is some causal association with mortality, and that has quite clearly not been established,” stressed Dr. Simpson, who is president of the American College of Chest Physicians but was not speaking for the organization.

He added: “The data are interesting, but not actionable. It is common practice in critical care medicine to adjust water and salt intake to maintain serum sodium within the normal range, so the paper really doesn’t change any behavior.”

Dr. Tzoulis said in an interview that, despite not having electronic medical record data on diuretic use or fluid input and output, “our acute physicians and intensivists at both study sites have been adamant that they’ve not routinely used diuretics in COVID-19 patients. Diuretics have been sparingly used in our cohort, and also the frequency of pulmonary edema was reported as below 5%.”

Regarding volume of fluid intake, Dr. Tzoulis noted, “At our hospital sites, the strategy has been that of cautious fluid resuscitation. In fact, the amount of fluid given has been reported by our physicians and intensivists as ‘on purpose much more conservative than the usual one adopted in patients with community-acquired pneumonia at risk of respiratory failure.’ ”
 

Hyper- and hyponatremia linked to adverse COVID-19 outcomes

In the study, 5.3% of the 488 patients had hypernatremia at hospital presentation, and 24.6% had hyponatremia. Of note, only 19% of those with hyponatremia underwent laboratory workup to determine the etiology. Of those, three quarters had hypovolemic hyponatremia, determined on the basis of a urinary sodium cutoff of 30 mmol/L.

The total in-hospital mortality rate was 31.1%. There was a strong, although nonsignificant, trend toward higher mortality in association with sodium status at admission. Death rates were 28.4%, 30.8%, and 46.1% for those who were normonatremic, hyponatremic, and hypernatremic, respectively (P = .07). Baseline serum sodium levels didn’t differ between survivors (137 mmol/L) and nonsurvivors (138 mmol/L).

In multivariable analysis, the occurrence of hypernatremia at any point during the first 5 days in the hospital was among three independent risk factors for higher in-hospital mortality (adjusted hazard ratio, 2.74; P = .02). The other risk factors were older age and higher CRP level.

Overall, hyponatremia was not associated with death (P = .41).

During hospitalization, 37.9% of patients remained normonatremic; 36.9% experienced hyponatremia; 10.9% had hypernatremia; and 14.3% had both conditions at some point during their stay.

In-hospital mortality was 21% among those with normonatremia, compared with 56.6% for those with hypernatremia (odds ratio, 3.05; P = .0038) and 45.7% for those with both (OR, 2.25; P < .0001).

The 28.3% mortality rate in the overall group that experienced hyponatremia didn’t differ significantly from the 21.1% in the normonatremic group (OR, 1.34; P = .16). However, the death rate was 40.9% among the subgroup that developed hypovolemic hyponatremia, significantly higher than the normonatremic group (OR, 2.59, P = .0017).

The incidence of hyponatremia decreased from 24.6% at admission to 14.1% 5 days later, whereas the frequency of hypernatremia rose from 5.3% to 13.8%.
 

Key finding: Link between hospital-acquired hypernatremia and death

“The key novel finding of our study was that hospital-acquired hypernatremia, rather than hypernatremia at admission, was a predictor for in-hospital mortality, with the worst prognosis being reported in patients with the largest increase in serum sodium in the first 5 days of hospitalization,” noted Dr. Tzoulis and colleagues.

Hypernatremia was present in 29.6% of nonsurvivors, compared with 5.2% in survivors.

Among 120 patients with hyponatremia at admission, 31.7% received advanced respiratory support, compared with 17.5% and 7.7% of those with normonatremia or hypernatremia, respectively (OR, 2.18; P = .0011).

In contrast, there was no difference in the proportions needing ventilatory support between those with hypernatremia and those with normonatremia (16.7% vs. 12.4%; OR, 1.44; P = .39).

Acute kidney injury occurred in 181 patients (37.1%). It was not related to serum sodium concentration at any time point.

Dr. Tzoulis and Dr. Simpson disclosed no relevant financial relationships.

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

Both high and low serum sodium levels are associated with adverse outcomes for hospitalized patients with COVID-19, new research suggests.

In the retrospective study of 488 patients hospitalized with COVID-19 at one of two London hospitals between February and May 2020, hypernatremia (defined as serum sodium level >145 mmol/L) at any time point during hospital stay was associated with a threefold increase in inpatient mortality.

Hyponatremia (serum sodium level <135 mmol/L) was associated with twice the likelihood of requiring advanced ventilatory support. In-hospital mortality was also increased among patients with hypovolemic hyponatremia.

“Serum sodium values could be used in clinical practice to identify patients with COVID-19 at high risk of poor outcomes who would benefit from more intensive monitoring and judicious rehydration,” Ploutarchos Tzoulis, MD, PhD, and colleagues wrote in their article, which was published online on Feb. 24, 2021, in the Journal of Clinical Endocrinology and Metabolism.

The findings will be presented at the upcoming news conference held by the Endocrine Society
 

Should sodium be included in a risk calculator for COVID-19?

Dr. Tzoulis, professor of endocrinology at the University College London Medical School, said in an interview that “sodium could be incorporated in risk calculators across other routine biomarkers, such as white cell count, lymphocytes, and CRP [C-reactive protein], in order to provide a tool for dynamic risk stratification throughout the clinical course of COVID-19 and assist clinical decision-making.”

Moreover, he said, “we should follow less conservative strategies in the rate and amount of fluid resuscitation in order to prevent hypernatremia, which is induced by negative fluid balance and can often be iatrogenic.”

Asked to comment, Steven Q. Simpson, MD, professor of medicine in the division of pulmonary, critical care, and sleep medicine at the University of Kansas, Kansas City, said that the article is missing key results that would assist in interpreting of the findings.

“Data regarding diuretic use and sparing of fluid administration are not in the paper. ... It is simply not possible to tell whether serum sodium is a ‘predictor’ ... or if it is a side effect of other issues or actions taken by physicians in patients who are progressing poorly.

“To say that sodium needs to be included in a risk calculator is to subtly suggest that there is some causal association with mortality, and that has quite clearly not been established,” stressed Dr. Simpson, who is president of the American College of Chest Physicians but was not speaking for the organization.

He added: “The data are interesting, but not actionable. It is common practice in critical care medicine to adjust water and salt intake to maintain serum sodium within the normal range, so the paper really doesn’t change any behavior.”

Dr. Tzoulis said in an interview that, despite not having electronic medical record data on diuretic use or fluid input and output, “our acute physicians and intensivists at both study sites have been adamant that they’ve not routinely used diuretics in COVID-19 patients. Diuretics have been sparingly used in our cohort, and also the frequency of pulmonary edema was reported as below 5%.”

Regarding volume of fluid intake, Dr. Tzoulis noted, “At our hospital sites, the strategy has been that of cautious fluid resuscitation. In fact, the amount of fluid given has been reported by our physicians and intensivists as ‘on purpose much more conservative than the usual one adopted in patients with community-acquired pneumonia at risk of respiratory failure.’ ”
 

Hyper- and hyponatremia linked to adverse COVID-19 outcomes

In the study, 5.3% of the 488 patients had hypernatremia at hospital presentation, and 24.6% had hyponatremia. Of note, only 19% of those with hyponatremia underwent laboratory workup to determine the etiology. Of those, three quarters had hypovolemic hyponatremia, determined on the basis of a urinary sodium cutoff of 30 mmol/L.

The total in-hospital mortality rate was 31.1%. There was a strong, although nonsignificant, trend toward higher mortality in association with sodium status at admission. Death rates were 28.4%, 30.8%, and 46.1% for those who were normonatremic, hyponatremic, and hypernatremic, respectively (P = .07). Baseline serum sodium levels didn’t differ between survivors (137 mmol/L) and nonsurvivors (138 mmol/L).

In multivariable analysis, the occurrence of hypernatremia at any point during the first 5 days in the hospital was among three independent risk factors for higher in-hospital mortality (adjusted hazard ratio, 2.74; P = .02). The other risk factors were older age and higher CRP level.

Overall, hyponatremia was not associated with death (P = .41).

During hospitalization, 37.9% of patients remained normonatremic; 36.9% experienced hyponatremia; 10.9% had hypernatremia; and 14.3% had both conditions at some point during their stay.

In-hospital mortality was 21% among those with normonatremia, compared with 56.6% for those with hypernatremia (odds ratio, 3.05; P = .0038) and 45.7% for those with both (OR, 2.25; P < .0001).

The 28.3% mortality rate in the overall group that experienced hyponatremia didn’t differ significantly from the 21.1% in the normonatremic group (OR, 1.34; P = .16). However, the death rate was 40.9% among the subgroup that developed hypovolemic hyponatremia, significantly higher than the normonatremic group (OR, 2.59, P = .0017).

The incidence of hyponatremia decreased from 24.6% at admission to 14.1% 5 days later, whereas the frequency of hypernatremia rose from 5.3% to 13.8%.
 

Key finding: Link between hospital-acquired hypernatremia and death

“The key novel finding of our study was that hospital-acquired hypernatremia, rather than hypernatremia at admission, was a predictor for in-hospital mortality, with the worst prognosis being reported in patients with the largest increase in serum sodium in the first 5 days of hospitalization,” noted Dr. Tzoulis and colleagues.

Hypernatremia was present in 29.6% of nonsurvivors, compared with 5.2% in survivors.

Among 120 patients with hyponatremia at admission, 31.7% received advanced respiratory support, compared with 17.5% and 7.7% of those with normonatremia or hypernatremia, respectively (OR, 2.18; P = .0011).

In contrast, there was no difference in the proportions needing ventilatory support between those with hypernatremia and those with normonatremia (16.7% vs. 12.4%; OR, 1.44; P = .39).

Acute kidney injury occurred in 181 patients (37.1%). It was not related to serum sodium concentration at any time point.

Dr. Tzoulis and Dr. Simpson disclosed no relevant financial relationships.

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

Both high and low serum sodium levels are associated with adverse outcomes for hospitalized patients with COVID-19, new research suggests.

In the retrospective study of 488 patients hospitalized with COVID-19 at one of two London hospitals between February and May 2020, hypernatremia (defined as serum sodium level >145 mmol/L) at any time point during hospital stay was associated with a threefold increase in inpatient mortality.

Hyponatremia (serum sodium level <135 mmol/L) was associated with twice the likelihood of requiring advanced ventilatory support. In-hospital mortality was also increased among patients with hypovolemic hyponatremia.

“Serum sodium values could be used in clinical practice to identify patients with COVID-19 at high risk of poor outcomes who would benefit from more intensive monitoring and judicious rehydration,” Ploutarchos Tzoulis, MD, PhD, and colleagues wrote in their article, which was published online on Feb. 24, 2021, in the Journal of Clinical Endocrinology and Metabolism.

The findings will be presented at the upcoming news conference held by the Endocrine Society
 

Should sodium be included in a risk calculator for COVID-19?

Dr. Tzoulis, professor of endocrinology at the University College London Medical School, said in an interview that “sodium could be incorporated in risk calculators across other routine biomarkers, such as white cell count, lymphocytes, and CRP [C-reactive protein], in order to provide a tool for dynamic risk stratification throughout the clinical course of COVID-19 and assist clinical decision-making.”

Moreover, he said, “we should follow less conservative strategies in the rate and amount of fluid resuscitation in order to prevent hypernatremia, which is induced by negative fluid balance and can often be iatrogenic.”

Asked to comment, Steven Q. Simpson, MD, professor of medicine in the division of pulmonary, critical care, and sleep medicine at the University of Kansas, Kansas City, said that the article is missing key results that would assist in interpreting of the findings.

“Data regarding diuretic use and sparing of fluid administration are not in the paper. ... It is simply not possible to tell whether serum sodium is a ‘predictor’ ... or if it is a side effect of other issues or actions taken by physicians in patients who are progressing poorly.

“To say that sodium needs to be included in a risk calculator is to subtly suggest that there is some causal association with mortality, and that has quite clearly not been established,” stressed Dr. Simpson, who is president of the American College of Chest Physicians but was not speaking for the organization.

He added: “The data are interesting, but not actionable. It is common practice in critical care medicine to adjust water and salt intake to maintain serum sodium within the normal range, so the paper really doesn’t change any behavior.”

Dr. Tzoulis said in an interview that, despite not having electronic medical record data on diuretic use or fluid input and output, “our acute physicians and intensivists at both study sites have been adamant that they’ve not routinely used diuretics in COVID-19 patients. Diuretics have been sparingly used in our cohort, and also the frequency of pulmonary edema was reported as below 5%.”

Regarding volume of fluid intake, Dr. Tzoulis noted, “At our hospital sites, the strategy has been that of cautious fluid resuscitation. In fact, the amount of fluid given has been reported by our physicians and intensivists as ‘on purpose much more conservative than the usual one adopted in patients with community-acquired pneumonia at risk of respiratory failure.’ ”
 

Hyper- and hyponatremia linked to adverse COVID-19 outcomes

In the study, 5.3% of the 488 patients had hypernatremia at hospital presentation, and 24.6% had hyponatremia. Of note, only 19% of those with hyponatremia underwent laboratory workup to determine the etiology. Of those, three quarters had hypovolemic hyponatremia, determined on the basis of a urinary sodium cutoff of 30 mmol/L.

The total in-hospital mortality rate was 31.1%. There was a strong, although nonsignificant, trend toward higher mortality in association with sodium status at admission. Death rates were 28.4%, 30.8%, and 46.1% for those who were normonatremic, hyponatremic, and hypernatremic, respectively (P = .07). Baseline serum sodium levels didn’t differ between survivors (137 mmol/L) and nonsurvivors (138 mmol/L).

In multivariable analysis, the occurrence of hypernatremia at any point during the first 5 days in the hospital was among three independent risk factors for higher in-hospital mortality (adjusted hazard ratio, 2.74; P = .02). The other risk factors were older age and higher CRP level.

Overall, hyponatremia was not associated with death (P = .41).

During hospitalization, 37.9% of patients remained normonatremic; 36.9% experienced hyponatremia; 10.9% had hypernatremia; and 14.3% had both conditions at some point during their stay.

In-hospital mortality was 21% among those with normonatremia, compared with 56.6% for those with hypernatremia (odds ratio, 3.05; P = .0038) and 45.7% for those with both (OR, 2.25; P < .0001).

The 28.3% mortality rate in the overall group that experienced hyponatremia didn’t differ significantly from the 21.1% in the normonatremic group (OR, 1.34; P = .16). However, the death rate was 40.9% among the subgroup that developed hypovolemic hyponatremia, significantly higher than the normonatremic group (OR, 2.59, P = .0017).

The incidence of hyponatremia decreased from 24.6% at admission to 14.1% 5 days later, whereas the frequency of hypernatremia rose from 5.3% to 13.8%.
 

Key finding: Link between hospital-acquired hypernatremia and death

“The key novel finding of our study was that hospital-acquired hypernatremia, rather than hypernatremia at admission, was a predictor for in-hospital mortality, with the worst prognosis being reported in patients with the largest increase in serum sodium in the first 5 days of hospitalization,” noted Dr. Tzoulis and colleagues.

Hypernatremia was present in 29.6% of nonsurvivors, compared with 5.2% in survivors.

Among 120 patients with hyponatremia at admission, 31.7% received advanced respiratory support, compared with 17.5% and 7.7% of those with normonatremia or hypernatremia, respectively (OR, 2.18; P = .0011).

In contrast, there was no difference in the proportions needing ventilatory support between those with hypernatremia and those with normonatremia (16.7% vs. 12.4%; OR, 1.44; P = .39).

Acute kidney injury occurred in 181 patients (37.1%). It was not related to serum sodium concentration at any time point.

Dr. Tzoulis and Dr. Simpson disclosed no relevant financial relationships.

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

Seven weeks appears to be the ideal amount of time to delay surgery, when possible, after someone tests positive for COVID-19, researchers in the United Kingdom report.

BraunS/Getty Images

Risk for death was about 3.5 to 4 times higher in the first 6 weeks after surgery among more than 3,000 people with a preoperative COVID-19 diagnosis compared with patients without COVID-19. After 7 weeks, the 30-day mortality rate dropped to a baseline level.

The study was published online March 9 in Anaesthesia.

Surgery should be further delayed for people who remain symptomatic at 7 weeks post diagnosis, lead author Dmitri Nepogodiev, MBChB, said in an interview.

“In this group we recommend waiting until COVID-19 symptoms resolve, if possible. However, our study did not capture specific data on long COVID … so we are unable to make specific recommendations for this group,” said Dr. Nepogodiev, research fellow at the NIHR Global Health Research Unit on Global Surgery at the University of Birmingham (England).

“This should be an area for future research,” he added.

The international, multicenter, prospective cohort study is notable for its sheer size – more than 15,000 investigators reported outcomes for 140,231 surgical patients from 1,674 hospitals across 116 countries. In total, 2.2% of these patients tested positive for SARS-CoV-2 prior to surgery.

Surgery of any type performed in October 2020 was assessed. A greater proportion of patients with a preoperative COVID-19 diagnosis had emergency surgery, 44%, compared with 30% of people who never had a COVID-19 diagnosis.

Most patients were asymptomatic at the time of surgery, either because they never experienced COVID-19 symptoms or their symptoms resolved. The 30-day mortality rate was the primary outcome.
 

Death rates among surgical patients with preoperative COVID-19 diagnosis

Comparing the timing of surgery after COVID-19 diagnosis vs. 30-day mortality yielded the following results:

• 0 to 2 weeks – 9.1% mortality.
• 3 to 4 weeks – 6.9%.
• 5 to 6 weeks – 5.5%.
• 7 weeks or longer – 2.0%..

For comparison, the 30-day mortality rate for surgical patients without a preoperative COVID-19 diagnosis was 1.4%. A COVID-19 diagnosis more than 7 weeks before surgery did not make a significant difference on outcomes.
 

The ‘why’ remains unknown

The reasons for the association between a COVID-19 diagnosis and higher postoperative death rates remain unknown. However, Dr. Nepogodiev speculated that it could be related to “some degree of lung injury, even if patients are initially asymptomatic.”

Intubation and mechanical ventilation during surgery could exacerbate the existing lung injury, he said, thereby leading to more severe COVID-19.

In fact, Dr. Nepogodiev and colleagues found that postoperative pulmonary complications followed a pattern similar to the findings on death. They reported higher rates of pneumonia, acute respiratory distress syndrome, and unexpected reventilation in the first 6 weeks following a COVID-19 diagnosis. Again, at 7 weeks and beyond, the rates returned to be relatively the same as those for people who never had COVID-19.

“Waiting for 7 or more weeks may allow time for the initial COVID-19 injury to resolve,” Dr. Nepogodiev said.
 

‘An important study’

“This is an important study of postoperative mortality among patients recovered from COVID-19,” Adrian Diaz, MD, MPH, said in an interview when asked to comment.

The large cohort and numerous practice settings are among the strengths of the research, said Dr. Diaz, of the University of Michigan Institute for Healthcare Policy and Innovation in Ann Arbor. He was lead author of a June 2020 review article on elective surgery in the time of COVID-19, published in The American Journal of Surgery.

“As with nearly all studies of this nature, results must be interpreted on a case-by-case basis for individual patients. However, this study does add important information for patients and providers in helping them have an informed discussion on the timing of surgery,” said Dr. Diaz, a fellow in the Center for Healthcare Outcomes and Policy and a resident in general surgery at the Ohio State University, Columbus.

Dr. Nepogodiev and colleagues included both urgent and elective surgeries in the study. Dr. Diaz said this was a potential limitation because emergency operations “should never be delayed, by definition.” Lack of indications for the surgeries and information on cause of death were additional limitations.

Future research should evaluate any benefit in delaying surgery longer than 7 or more weeks, Dr. Diaz added, perhaps looking specifically at 10, 12, or 14 weeks, or considering outcomes as a continuous variable. This would help health care providers “garner more insight into risk and benefits of delaying surgery beyond 7 weeks.”

Dr. Nepogodiev and Dr. Diaz disclosed no relevant financial relationships. The study had multiple funding sources, including the National Institute for Health Research Global Health Research Unit, the Association of Upper Gastrointestinal Surgeons, the British Association of Surgical Oncology, and Medtronic.

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

Seven weeks appears to be the ideal amount of time to delay surgery, when possible, after someone tests positive for COVID-19, researchers in the United Kingdom report.

BraunS/Getty Images

Risk for death was about 3.5 to 4 times higher in the first 6 weeks after surgery among more than 3,000 people with a preoperative COVID-19 diagnosis compared with patients without COVID-19. After 7 weeks, the 30-day mortality rate dropped to a baseline level.

The study was published online March 9 in Anaesthesia.

Surgery should be further delayed for people who remain symptomatic at 7 weeks post diagnosis, lead author Dmitri Nepogodiev, MBChB, said in an interview.

“In this group we recommend waiting until COVID-19 symptoms resolve, if possible. However, our study did not capture specific data on long COVID … so we are unable to make specific recommendations for this group,” said Dr. Nepogodiev, research fellow at the NIHR Global Health Research Unit on Global Surgery at the University of Birmingham (England).

“This should be an area for future research,” he added.

The international, multicenter, prospective cohort study is notable for its sheer size – more than 15,000 investigators reported outcomes for 140,231 surgical patients from 1,674 hospitals across 116 countries. In total, 2.2% of these patients tested positive for SARS-CoV-2 prior to surgery.

Surgery of any type performed in October 2020 was assessed. A greater proportion of patients with a preoperative COVID-19 diagnosis had emergency surgery, 44%, compared with 30% of people who never had a COVID-19 diagnosis.

Most patients were asymptomatic at the time of surgery, either because they never experienced COVID-19 symptoms or their symptoms resolved. The 30-day mortality rate was the primary outcome.
 

Death rates among surgical patients with preoperative COVID-19 diagnosis

Comparing the timing of surgery after COVID-19 diagnosis vs. 30-day mortality yielded the following results:

• 0 to 2 weeks – 9.1% mortality.
• 3 to 4 weeks – 6.9%.
• 5 to 6 weeks – 5.5%.
• 7 weeks or longer – 2.0%..

For comparison, the 30-day mortality rate for surgical patients without a preoperative COVID-19 diagnosis was 1.4%. A COVID-19 diagnosis more than 7 weeks before surgery did not make a significant difference on outcomes.
 

The ‘why’ remains unknown

The reasons for the association between a COVID-19 diagnosis and higher postoperative death rates remain unknown. However, Dr. Nepogodiev speculated that it could be related to “some degree of lung injury, even if patients are initially asymptomatic.”

Intubation and mechanical ventilation during surgery could exacerbate the existing lung injury, he said, thereby leading to more severe COVID-19.

In fact, Dr. Nepogodiev and colleagues found that postoperative pulmonary complications followed a pattern similar to the findings on death. They reported higher rates of pneumonia, acute respiratory distress syndrome, and unexpected reventilation in the first 6 weeks following a COVID-19 diagnosis. Again, at 7 weeks and beyond, the rates returned to be relatively the same as those for people who never had COVID-19.

“Waiting for 7 or more weeks may allow time for the initial COVID-19 injury to resolve,” Dr. Nepogodiev said.
 

‘An important study’

“This is an important study of postoperative mortality among patients recovered from COVID-19,” Adrian Diaz, MD, MPH, said in an interview when asked to comment.

The large cohort and numerous practice settings are among the strengths of the research, said Dr. Diaz, of the University of Michigan Institute for Healthcare Policy and Innovation in Ann Arbor. He was lead author of a June 2020 review article on elective surgery in the time of COVID-19, published in The American Journal of Surgery.

“As with nearly all studies of this nature, results must be interpreted on a case-by-case basis for individual patients. However, this study does add important information for patients and providers in helping them have an informed discussion on the timing of surgery,” said Dr. Diaz, a fellow in the Center for Healthcare Outcomes and Policy and a resident in general surgery at the Ohio State University, Columbus.

Dr. Nepogodiev and colleagues included both urgent and elective surgeries in the study. Dr. Diaz said this was a potential limitation because emergency operations “should never be delayed, by definition.” Lack of indications for the surgeries and information on cause of death were additional limitations.

Future research should evaluate any benefit in delaying surgery longer than 7 or more weeks, Dr. Diaz added, perhaps looking specifically at 10, 12, or 14 weeks, or considering outcomes as a continuous variable. This would help health care providers “garner more insight into risk and benefits of delaying surgery beyond 7 weeks.”

Dr. Nepogodiev and Dr. Diaz disclosed no relevant financial relationships. The study had multiple funding sources, including the National Institute for Health Research Global Health Research Unit, the Association of Upper Gastrointestinal Surgeons, the British Association of Surgical Oncology, and Medtronic.

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

Seven weeks appears to be the ideal amount of time to delay surgery, when possible, after someone tests positive for COVID-19, researchers in the United Kingdom report.

BraunS/Getty Images

Risk for death was about 3.5 to 4 times higher in the first 6 weeks after surgery among more than 3,000 people with a preoperative COVID-19 diagnosis compared with patients without COVID-19. After 7 weeks, the 30-day mortality rate dropped to a baseline level.

The study was published online March 9 in Anaesthesia.

Surgery should be further delayed for people who remain symptomatic at 7 weeks post diagnosis, lead author Dmitri Nepogodiev, MBChB, said in an interview.

“In this group we recommend waiting until COVID-19 symptoms resolve, if possible. However, our study did not capture specific data on long COVID … so we are unable to make specific recommendations for this group,” said Dr. Nepogodiev, research fellow at the NIHR Global Health Research Unit on Global Surgery at the University of Birmingham (England).

“This should be an area for future research,” he added.

The international, multicenter, prospective cohort study is notable for its sheer size – more than 15,000 investigators reported outcomes for 140,231 surgical patients from 1,674 hospitals across 116 countries. In total, 2.2% of these patients tested positive for SARS-CoV-2 prior to surgery.

Surgery of any type performed in October 2020 was assessed. A greater proportion of patients with a preoperative COVID-19 diagnosis had emergency surgery, 44%, compared with 30% of people who never had a COVID-19 diagnosis.

Most patients were asymptomatic at the time of surgery, either because they never experienced COVID-19 symptoms or their symptoms resolved. The 30-day mortality rate was the primary outcome.
 

Death rates among surgical patients with preoperative COVID-19 diagnosis

Comparing the timing of surgery after COVID-19 diagnosis vs. 30-day mortality yielded the following results:

• 0 to 2 weeks – 9.1% mortality.
• 3 to 4 weeks – 6.9%.
• 5 to 6 weeks – 5.5%.
• 7 weeks or longer – 2.0%..

For comparison, the 30-day mortality rate for surgical patients without a preoperative COVID-19 diagnosis was 1.4%. A COVID-19 diagnosis more than 7 weeks before surgery did not make a significant difference on outcomes.
 

The ‘why’ remains unknown

The reasons for the association between a COVID-19 diagnosis and higher postoperative death rates remain unknown. However, Dr. Nepogodiev speculated that it could be related to “some degree of lung injury, even if patients are initially asymptomatic.”

Intubation and mechanical ventilation during surgery could exacerbate the existing lung injury, he said, thereby leading to more severe COVID-19.

In fact, Dr. Nepogodiev and colleagues found that postoperative pulmonary complications followed a pattern similar to the findings on death. They reported higher rates of pneumonia, acute respiratory distress syndrome, and unexpected reventilation in the first 6 weeks following a COVID-19 diagnosis. Again, at 7 weeks and beyond, the rates returned to be relatively the same as those for people who never had COVID-19.

“Waiting for 7 or more weeks may allow time for the initial COVID-19 injury to resolve,” Dr. Nepogodiev said.
 

‘An important study’

“This is an important study of postoperative mortality among patients recovered from COVID-19,” Adrian Diaz, MD, MPH, said in an interview when asked to comment.

The large cohort and numerous practice settings are among the strengths of the research, said Dr. Diaz, of the University of Michigan Institute for Healthcare Policy and Innovation in Ann Arbor. He was lead author of a June 2020 review article on elective surgery in the time of COVID-19, published in The American Journal of Surgery.

“As with nearly all studies of this nature, results must be interpreted on a case-by-case basis for individual patients. However, this study does add important information for patients and providers in helping them have an informed discussion on the timing of surgery,” said Dr. Diaz, a fellow in the Center for Healthcare Outcomes and Policy and a resident in general surgery at the Ohio State University, Columbus.

Dr. Nepogodiev and colleagues included both urgent and elective surgeries in the study. Dr. Diaz said this was a potential limitation because emergency operations “should never be delayed, by definition.” Lack of indications for the surgeries and information on cause of death were additional limitations.

Future research should evaluate any benefit in delaying surgery longer than 7 or more weeks, Dr. Diaz added, perhaps looking specifically at 10, 12, or 14 weeks, or considering outcomes as a continuous variable. This would help health care providers “garner more insight into risk and benefits of delaying surgery beyond 7 weeks.”

Dr. Nepogodiev and Dr. Diaz disclosed no relevant financial relationships. The study had multiple funding sources, including the National Institute for Health Research Global Health Research Unit, the Association of Upper Gastrointestinal Surgeons, the British Association of Surgical Oncology, and Medtronic.

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

A novel minimal monitoring (MINMON) approach to hepatitis C virus (HCV) treatment was safe and achieved sustained virology response (SVR) compared to current clinical standards in treatment-naive patients without evidence of decompensated cirrhosis, according to a recent study.

©Jezperklauzen/ThinkStock

“This model may allow for HCV elimination, while minimizing resource use and face-to-face contact,” said investigator Sunil S. Solomon, MBBS, PhD, of Johns Hopkins University in Baltimore. “The COVID-19 pandemic has highlighted the urgent need for simple and safe models of HCV [care] delivery.”

Dr. Solomon described the new approach to HCV treatment during a presentation at this year’s Conference on Retroviruses and Opportunistic Infections virtual meeting.
 

Study design

ACTG A5360 was an international, single-arm, open-label, phase 4 trial that enrolled 400 patients across 38 treatment sites.

The researchers evaluated the efficacy and safety of the MINMON approach in treatment-naive individuals who had no evidence of decompensated cirrhosis. Study participants received a fixed-dose, single-tablet regimen of sofosbuvir 400 mg/velpatasvir 100 mg once daily for 12 weeks.

The MINMON approach comprised four key elements: no pretreatment genotyping, all tablets dispensed at study entry, no scheduled on-treatment clinic visits/labs, and two remote contacts at weeks 4 (adherence evaluation) and 22 (scheduled SVR visit). Unplanned visits for patients concerns were permitted.

Key eligibility criteria included active HCV infection (HCV RNA > 1,000 IU/mL) and no prior HCV treatment history. Persons with HIV coinfection (50% or less of sample) and compensated cirrhosis (20% or less of sample) were also eligible. Persons with chronic hepatitis B virus (HBV) infection and decompensated cirrhosis were excluded.

The primary efficacy endpoint was SVR, defined as HCV RNA less than the lower limit of quantification in the first sample at least 22 weeks post treatment initiation. The primary safety endpoint was any serious adverse events (AEs) occurring between treatment initiation and week 28.
 

Results

Among 400 patients enrolled, 399 (99.8%) were included in the primary efficacy analysis and 397 (99.3%) were included in the safety analysis. The median age of participants was 47 years, and 35% were female sex at birth. At baseline, 166 (42%) patients had HIV coinfection and 34 (9%) had compensated cirrhosis.

After analysis, the researchers found that remote contact was successful at weeks 4 and 22 for 394 (98.7%) and 335 (84.0%) participants, respectively.

In total, 15 (3.8%) participants recorded 21 unplanned visits, 3 (14.3%) of which were due to AEs, none of which were treatment related. Three participants reported losing study medications and one participant prematurely discontinued therapy due to an AE.

HCV RNA data at SVR were available for 396 participants. Overall, 379 patients (95.0%) achieved SVR (95% confidence interval [CI], 92.4%-96.7%).

“The study was not powered for SVR by subgroups, which explains why we observed wide confidence intervals in our forest plot,” Dr. Solomon said.

With respect to safety, serious AEs were reported in 14 (3.5%) participants through week 24 visit, none of which were treatment related or resulted in death.

Dr. Solomon acknowledged that a key limitation of the study was the single-arm design. As a result, there was no direct comparison to standard monitoring practices. In addition, these results may not be generalizable to all nonresearch treatment sites.

“The COVID-19 pandemic has required us to pivot clinical programs to minimize in-person contact, and promote more remote approaches, which is really the essence of the MINMON approach,” Dr. Solomon explained.

“There are really wonderful results in the population that was studied, but may reflect a more adherent patient population,” said moderator Robert T. Schooley, MD, of the University of California, San Diego.

During a discussion, Dr. Solomon noted that the MINMON approach may be further explored in patients who are actively injecting drugs, as these patients were not well represented in the present study.

Dr. Solomon disclosed financial relationships with Gilead Sciences and Abbott Diagnostics. The study was funded by the National Institutes of Health and Gilead Sciences.

A novel minimal monitoring (MINMON) approach to hepatitis C virus (HCV) treatment was safe and achieved sustained virology response (SVR) compared to current clinical standards in treatment-naive patients without evidence of decompensated cirrhosis, according to a recent study.

©Jezperklauzen/ThinkStock

“This model may allow for HCV elimination, while minimizing resource use and face-to-face contact,” said investigator Sunil S. Solomon, MBBS, PhD, of Johns Hopkins University in Baltimore. “The COVID-19 pandemic has highlighted the urgent need for simple and safe models of HCV [care] delivery.”

Dr. Solomon described the new approach to HCV treatment during a presentation at this year’s Conference on Retroviruses and Opportunistic Infections virtual meeting.
 

Study design

ACTG A5360 was an international, single-arm, open-label, phase 4 trial that enrolled 400 patients across 38 treatment sites.

The researchers evaluated the efficacy and safety of the MINMON approach in treatment-naive individuals who had no evidence of decompensated cirrhosis. Study participants received a fixed-dose, single-tablet regimen of sofosbuvir 400 mg/velpatasvir 100 mg once daily for 12 weeks.

The MINMON approach comprised four key elements: no pretreatment genotyping, all tablets dispensed at study entry, no scheduled on-treatment clinic visits/labs, and two remote contacts at weeks 4 (adherence evaluation) and 22 (scheduled SVR visit). Unplanned visits for patients concerns were permitted.

Key eligibility criteria included active HCV infection (HCV RNA > 1,000 IU/mL) and no prior HCV treatment history. Persons with HIV coinfection (50% or less of sample) and compensated cirrhosis (20% or less of sample) were also eligible. Persons with chronic hepatitis B virus (HBV) infection and decompensated cirrhosis were excluded.

The primary efficacy endpoint was SVR, defined as HCV RNA less than the lower limit of quantification in the first sample at least 22 weeks post treatment initiation. The primary safety endpoint was any serious adverse events (AEs) occurring between treatment initiation and week 28.
 

Results

Among 400 patients enrolled, 399 (99.8%) were included in the primary efficacy analysis and 397 (99.3%) were included in the safety analysis. The median age of participants was 47 years, and 35% were female sex at birth. At baseline, 166 (42%) patients had HIV coinfection and 34 (9%) had compensated cirrhosis.

After analysis, the researchers found that remote contact was successful at weeks 4 and 22 for 394 (98.7%) and 335 (84.0%) participants, respectively.

In total, 15 (3.8%) participants recorded 21 unplanned visits, 3 (14.3%) of which were due to AEs, none of which were treatment related. Three participants reported losing study medications and one participant prematurely discontinued therapy due to an AE.

HCV RNA data at SVR were available for 396 participants. Overall, 379 patients (95.0%) achieved SVR (95% confidence interval [CI], 92.4%-96.7%).

“The study was not powered for SVR by subgroups, which explains why we observed wide confidence intervals in our forest plot,” Dr. Solomon said.

With respect to safety, serious AEs were reported in 14 (3.5%) participants through week 24 visit, none of which were treatment related or resulted in death.

Dr. Solomon acknowledged that a key limitation of the study was the single-arm design. As a result, there was no direct comparison to standard monitoring practices. In addition, these results may not be generalizable to all nonresearch treatment sites.

“The COVID-19 pandemic has required us to pivot clinical programs to minimize in-person contact, and promote more remote approaches, which is really the essence of the MINMON approach,” Dr. Solomon explained.

“There are really wonderful results in the population that was studied, but may reflect a more adherent patient population,” said moderator Robert T. Schooley, MD, of the University of California, San Diego.

During a discussion, Dr. Solomon noted that the MINMON approach may be further explored in patients who are actively injecting drugs, as these patients were not well represented in the present study.

Dr. Solomon disclosed financial relationships with Gilead Sciences and Abbott Diagnostics. The study was funded by the National Institutes of Health and Gilead Sciences.

A novel minimal monitoring (MINMON) approach to hepatitis C virus (HCV) treatment was safe and achieved sustained virology response (SVR) compared to current clinical standards in treatment-naive patients without evidence of decompensated cirrhosis, according to a recent study.

©Jezperklauzen/ThinkStock

“This model may allow for HCV elimination, while minimizing resource use and face-to-face contact,” said investigator Sunil S. Solomon, MBBS, PhD, of Johns Hopkins University in Baltimore. “The COVID-19 pandemic has highlighted the urgent need for simple and safe models of HCV [care] delivery.”

Dr. Solomon described the new approach to HCV treatment during a presentation at this year’s Conference on Retroviruses and Opportunistic Infections virtual meeting.
 

Study design

ACTG A5360 was an international, single-arm, open-label, phase 4 trial that enrolled 400 patients across 38 treatment sites.

The researchers evaluated the efficacy and safety of the MINMON approach in treatment-naive individuals who had no evidence of decompensated cirrhosis. Study participants received a fixed-dose, single-tablet regimen of sofosbuvir 400 mg/velpatasvir 100 mg once daily for 12 weeks.

The MINMON approach comprised four key elements: no pretreatment genotyping, all tablets dispensed at study entry, no scheduled on-treatment clinic visits/labs, and two remote contacts at weeks 4 (adherence evaluation) and 22 (scheduled SVR visit). Unplanned visits for patients concerns were permitted.

Key eligibility criteria included active HCV infection (HCV RNA > 1,000 IU/mL) and no prior HCV treatment history. Persons with HIV coinfection (50% or less of sample) and compensated cirrhosis (20% or less of sample) were also eligible. Persons with chronic hepatitis B virus (HBV) infection and decompensated cirrhosis were excluded.

The primary efficacy endpoint was SVR, defined as HCV RNA less than the lower limit of quantification in the first sample at least 22 weeks post treatment initiation. The primary safety endpoint was any serious adverse events (AEs) occurring between treatment initiation and week 28.
 

Results

Among 400 patients enrolled, 399 (99.8%) were included in the primary efficacy analysis and 397 (99.3%) were included in the safety analysis. The median age of participants was 47 years, and 35% were female sex at birth. At baseline, 166 (42%) patients had HIV coinfection and 34 (9%) had compensated cirrhosis.

After analysis, the researchers found that remote contact was successful at weeks 4 and 22 for 394 (98.7%) and 335 (84.0%) participants, respectively.

In total, 15 (3.8%) participants recorded 21 unplanned visits, 3 (14.3%) of which were due to AEs, none of which were treatment related. Three participants reported losing study medications and one participant prematurely discontinued therapy due to an AE.

HCV RNA data at SVR were available for 396 participants. Overall, 379 patients (95.0%) achieved SVR (95% confidence interval [CI], 92.4%-96.7%).

“The study was not powered for SVR by subgroups, which explains why we observed wide confidence intervals in our forest plot,” Dr. Solomon said.

With respect to safety, serious AEs were reported in 14 (3.5%) participants through week 24 visit, none of which were treatment related or resulted in death.

Dr. Solomon acknowledged that a key limitation of the study was the single-arm design. As a result, there was no direct comparison to standard monitoring practices. In addition, these results may not be generalizable to all nonresearch treatment sites.

“The COVID-19 pandemic has required us to pivot clinical programs to minimize in-person contact, and promote more remote approaches, which is really the essence of the MINMON approach,” Dr. Solomon explained.

“There are really wonderful results in the population that was studied, but may reflect a more adherent patient population,” said moderator Robert T. Schooley, MD, of the University of California, San Diego.

During a discussion, Dr. Solomon noted that the MINMON approach may be further explored in patients who are actively injecting drugs, as these patients were not well represented in the present study.

Dr. Solomon disclosed financial relationships with Gilead Sciences and Abbott Diagnostics. The study was funded by the National Institutes of Health and Gilead Sciences.