Ob.Gyn. News

An updated Cochrane Systematic Review of magnesium sulfate administered before preterm birth for neuroprotection has reaffirmed that the compound significantly reduces the risk of cerebral palsy and has added the finding that it also may reduce the risk of severe neonatal intraventricular hemorrhage.

Still unknown, however, is whether the effects of magnesium sulfate vary according to patient characteristics such as gestational age, or by treatment characteristics such as timing and dose. “We need further research to determine exactly who to treat, and when and how, to ideally standardize clinical practice recommendations across the world,” said Emily S. Shepherd, PhD, lead author of the review.

Magnesium sulfate is widely used for preterm cerebral palsy prevention but variance in national and local recommendations for its use may impede its optimal uptake in some places, she and her co-investigators wrote in the review.

In the United States, the American College of Obstetricians and Gynecologists advises institutions to develop their own guidelines regarding inclusion criteria and treatment regimens “in accordance with one of the larger trials.” (ACOG’s Committee Opinion on Magnesium Sulfate Before Anticipated Preterm Birth for Neuroprotection was originally published in 2010 and was reaffirmed in 2023.)

In a Master Class column on magnesium sulfate for neuroprotection published earlier this year in Ob.Gyn. News, Irina Burd, MD, PhD, wrote that most hospitals in the United States have chosen a higher dose of magnesium sulfate administered up to 31 weeks’ gestation (6-g bolus, followed by 2 g/hour), in keeping with the protocols used in the BEAM trial published by the National Institute of Child Health and Human Development (NICHD). Dr. Burd is the Sylvan Frieman, MD, Endowed Professor and chair of the department of obstetrics, gynecology and reproductive sciences at the University of Maryland School of Medicine, Baltimore, Maryland.

The new Cochrane review included six randomized controlled trials (including the NICHD trial) covering 5917 pregnant participants and 6759 fetuses. Eligibility criteria varied, but all the RCTs included patients in preterm labor or with expected or planned imminent preterm birth at less than 34 weeks’ gestation.

Treatment regimens varied: three trials administered a 4-g loading dose only, and three included a maintenance dose (a 4-6-g loading dose and a 1-2 g/hour maintenance dose). “Although we attempted to explore variation through subgroup analyses, the ability to do this was limited,” the researchers wrote.

Up to 2 years of corrected age, magnesium sulfate reduced the risk of cerebral palsy compared with placebo (relative risk, 0.71; 95% confidence interval (CI), 0.57-0.89) and death or cerebral palsy (RR, 0.87; 95% CI, 0.77-0.98), with a high-certainty grade of evidence. The number needed to treat to prevent one case of cerebral palsy was 60 and the number needed to treat death or cerebral palsy was 56. The impact on severe intracranial hemorrhage (RR, 0.76; 95% CI, 0.60-0.98), a secondary outcome, was backed by moderate-certainty evidence.

Compared with the 2009 Cochrane review, the new study includes two new randomized controlled trials. One of which, the MAGENTA trial, administered magnesium sulfate at 30-34 weeks gestation and included new school-age follow-up data from two previously included trials. While the available data suggest little to no difference in outcomes at school age, more follow-up data are needed to assess this with greater certainty, the reviewers wrote.

While severe adverse outcomes (death, cardiac or respiratory arrest) for pregnant individuals appear not to have increased in pregnant patients who received magnesium sulfate (low-certainty evidence), the compound “probably increased maternal adverse effects severe enough to stop treatment,” the reviewers report (average RR, 3.21; 95% CI, 1.88-5.48; moderate-certainty evidence).

Side effects that were more frequent among women receiving magnesium sulfate include hypotension, tachycardia, warmth over body/flushing, nausea or vomiting, sweating, and dizziness.

“Treatment cessation due to such side effects was in the context of trials being conducted to establish benefit,” noted Dr. Shepherd, of the University of Adelaide in Australia. “With benefit now shown, these side effects may be viewed as comparatively minor/generally tolerable considering the potential benefits for children.”

Proving the neuroprotective value of magnesium sulfate took many years, Dr. Burd explained in the Master Class, as none of the randomized controlled trials analyzed in eventual meta-analyses and systematic reviews had reached their primary endpoints. It wasn’t until researchers obtained unpublished data and conducted these analyses and reviews that a significant effect of magnesium sulfate on cerebral palsy could be seen. Dr. Burd and other researchers are now working to better understand its biologic plausibility and precise mechanisms of action.

Dr. Shepherd disclosed that she is a former editor for Cochrane Pregnancy and Childbirth and current sign-off editor for Cochrane Central Editorial Service but reported having no involvement in the editorial processing of the review. Other authors disclosed that they were investigators for included trials and/or have published opinions in medical journals related to magnesium sulfate to reduce cerebral palsy. Dr. Burd reported no disclosures.

An updated Cochrane Systematic Review of magnesium sulfate administered before preterm birth for neuroprotection has reaffirmed that the compound significantly reduces the risk of cerebral palsy and has added the finding that it also may reduce the risk of severe neonatal intraventricular hemorrhage.

Still unknown, however, is whether the effects of magnesium sulfate vary according to patient characteristics such as gestational age, or by treatment characteristics such as timing and dose. “We need further research to determine exactly who to treat, and when and how, to ideally standardize clinical practice recommendations across the world,” said Emily S. Shepherd, PhD, lead author of the review.

Magnesium sulfate is widely used for preterm cerebral palsy prevention but variance in national and local recommendations for its use may impede its optimal uptake in some places, she and her co-investigators wrote in the review.

In the United States, the American College of Obstetricians and Gynecologists advises institutions to develop their own guidelines regarding inclusion criteria and treatment regimens “in accordance with one of the larger trials.” (ACOG’s Committee Opinion on Magnesium Sulfate Before Anticipated Preterm Birth for Neuroprotection was originally published in 2010 and was reaffirmed in 2023.)

In a Master Class column on magnesium sulfate for neuroprotection published earlier this year in Ob.Gyn. News, Irina Burd, MD, PhD, wrote that most hospitals in the United States have chosen a higher dose of magnesium sulfate administered up to 31 weeks’ gestation (6-g bolus, followed by 2 g/hour), in keeping with the protocols used in the BEAM trial published by the National Institute of Child Health and Human Development (NICHD). Dr. Burd is the Sylvan Frieman, MD, Endowed Professor and chair of the department of obstetrics, gynecology and reproductive sciences at the University of Maryland School of Medicine, Baltimore, Maryland.

The new Cochrane review included six randomized controlled trials (including the NICHD trial) covering 5917 pregnant participants and 6759 fetuses. Eligibility criteria varied, but all the RCTs included patients in preterm labor or with expected or planned imminent preterm birth at less than 34 weeks’ gestation.

Treatment regimens varied: three trials administered a 4-g loading dose only, and three included a maintenance dose (a 4-6-g loading dose and a 1-2 g/hour maintenance dose). “Although we attempted to explore variation through subgroup analyses, the ability to do this was limited,” the researchers wrote.

Up to 2 years of corrected age, magnesium sulfate reduced the risk of cerebral palsy compared with placebo (relative risk, 0.71; 95% confidence interval (CI), 0.57-0.89) and death or cerebral palsy (RR, 0.87; 95% CI, 0.77-0.98), with a high-certainty grade of evidence. The number needed to treat to prevent one case of cerebral palsy was 60 and the number needed to treat death or cerebral palsy was 56. The impact on severe intracranial hemorrhage (RR, 0.76; 95% CI, 0.60-0.98), a secondary outcome, was backed by moderate-certainty evidence.

Compared with the 2009 Cochrane review, the new study includes two new randomized controlled trials. One of which, the MAGENTA trial, administered magnesium sulfate at 30-34 weeks gestation and included new school-age follow-up data from two previously included trials. While the available data suggest little to no difference in outcomes at school age, more follow-up data are needed to assess this with greater certainty, the reviewers wrote.

While severe adverse outcomes (death, cardiac or respiratory arrest) for pregnant individuals appear not to have increased in pregnant patients who received magnesium sulfate (low-certainty evidence), the compound “probably increased maternal adverse effects severe enough to stop treatment,” the reviewers report (average RR, 3.21; 95% CI, 1.88-5.48; moderate-certainty evidence).

Side effects that were more frequent among women receiving magnesium sulfate include hypotension, tachycardia, warmth over body/flushing, nausea or vomiting, sweating, and dizziness.

“Treatment cessation due to such side effects was in the context of trials being conducted to establish benefit,” noted Dr. Shepherd, of the University of Adelaide in Australia. “With benefit now shown, these side effects may be viewed as comparatively minor/generally tolerable considering the potential benefits for children.”

Proving the neuroprotective value of magnesium sulfate took many years, Dr. Burd explained in the Master Class, as none of the randomized controlled trials analyzed in eventual meta-analyses and systematic reviews had reached their primary endpoints. It wasn’t until researchers obtained unpublished data and conducted these analyses and reviews that a significant effect of magnesium sulfate on cerebral palsy could be seen. Dr. Burd and other researchers are now working to better understand its biologic plausibility and precise mechanisms of action.

Dr. Shepherd disclosed that she is a former editor for Cochrane Pregnancy and Childbirth and current sign-off editor for Cochrane Central Editorial Service but reported having no involvement in the editorial processing of the review. Other authors disclosed that they were investigators for included trials and/or have published opinions in medical journals related to magnesium sulfate to reduce cerebral palsy. Dr. Burd reported no disclosures.

An updated Cochrane Systematic Review of magnesium sulfate administered before preterm birth for neuroprotection has reaffirmed that the compound significantly reduces the risk of cerebral palsy and has added the finding that it also may reduce the risk of severe neonatal intraventricular hemorrhage.

Still unknown, however, is whether the effects of magnesium sulfate vary according to patient characteristics such as gestational age, or by treatment characteristics such as timing and dose. “We need further research to determine exactly who to treat, and when and how, to ideally standardize clinical practice recommendations across the world,” said Emily S. Shepherd, PhD, lead author of the review.

Magnesium sulfate is widely used for preterm cerebral palsy prevention but variance in national and local recommendations for its use may impede its optimal uptake in some places, she and her co-investigators wrote in the review.

In the United States, the American College of Obstetricians and Gynecologists advises institutions to develop their own guidelines regarding inclusion criteria and treatment regimens “in accordance with one of the larger trials.” (ACOG’s Committee Opinion on Magnesium Sulfate Before Anticipated Preterm Birth for Neuroprotection was originally published in 2010 and was reaffirmed in 2023.)

In a Master Class column on magnesium sulfate for neuroprotection published earlier this year in Ob.Gyn. News, Irina Burd, MD, PhD, wrote that most hospitals in the United States have chosen a higher dose of magnesium sulfate administered up to 31 weeks’ gestation (6-g bolus, followed by 2 g/hour), in keeping with the protocols used in the BEAM trial published by the National Institute of Child Health and Human Development (NICHD). Dr. Burd is the Sylvan Frieman, MD, Endowed Professor and chair of the department of obstetrics, gynecology and reproductive sciences at the University of Maryland School of Medicine, Baltimore, Maryland.

The new Cochrane review included six randomized controlled trials (including the NICHD trial) covering 5917 pregnant participants and 6759 fetuses. Eligibility criteria varied, but all the RCTs included patients in preterm labor or with expected or planned imminent preterm birth at less than 34 weeks’ gestation.

Treatment regimens varied: three trials administered a 4-g loading dose only, and three included a maintenance dose (a 4-6-g loading dose and a 1-2 g/hour maintenance dose). “Although we attempted to explore variation through subgroup analyses, the ability to do this was limited,” the researchers wrote.

Up to 2 years of corrected age, magnesium sulfate reduced the risk of cerebral palsy compared with placebo (relative risk, 0.71; 95% confidence interval (CI), 0.57-0.89) and death or cerebral palsy (RR, 0.87; 95% CI, 0.77-0.98), with a high-certainty grade of evidence. The number needed to treat to prevent one case of cerebral palsy was 60 and the number needed to treat death or cerebral palsy was 56. The impact on severe intracranial hemorrhage (RR, 0.76; 95% CI, 0.60-0.98), a secondary outcome, was backed by moderate-certainty evidence.

Compared with the 2009 Cochrane review, the new study includes two new randomized controlled trials. One of which, the MAGENTA trial, administered magnesium sulfate at 30-34 weeks gestation and included new school-age follow-up data from two previously included trials. While the available data suggest little to no difference in outcomes at school age, more follow-up data are needed to assess this with greater certainty, the reviewers wrote.

While severe adverse outcomes (death, cardiac or respiratory arrest) for pregnant individuals appear not to have increased in pregnant patients who received magnesium sulfate (low-certainty evidence), the compound “probably increased maternal adverse effects severe enough to stop treatment,” the reviewers report (average RR, 3.21; 95% CI, 1.88-5.48; moderate-certainty evidence).

Side effects that were more frequent among women receiving magnesium sulfate include hypotension, tachycardia, warmth over body/flushing, nausea or vomiting, sweating, and dizziness.

“Treatment cessation due to such side effects was in the context of trials being conducted to establish benefit,” noted Dr. Shepherd, of the University of Adelaide in Australia. “With benefit now shown, these side effects may be viewed as comparatively minor/generally tolerable considering the potential benefits for children.”

Proving the neuroprotective value of magnesium sulfate took many years, Dr. Burd explained in the Master Class, as none of the randomized controlled trials analyzed in eventual meta-analyses and systematic reviews had reached their primary endpoints. It wasn’t until researchers obtained unpublished data and conducted these analyses and reviews that a significant effect of magnesium sulfate on cerebral palsy could be seen. Dr. Burd and other researchers are now working to better understand its biologic plausibility and precise mechanisms of action.

Dr. Shepherd disclosed that she is a former editor for Cochrane Pregnancy and Childbirth and current sign-off editor for Cochrane Central Editorial Service but reported having no involvement in the editorial processing of the review. Other authors disclosed that they were investigators for included trials and/or have published opinions in medical journals related to magnesium sulfate to reduce cerebral palsy. Dr. Burd reported no disclosures.

PARIS — Pregnancy is a period of asthma instability; it entails an increased risk for exacerbations. While therapeutic de-escalation, if not the outright cessation of maintenance treatment, is common, experts used the 19th Francophone Congress of Allergology to emphasize the importance of well-controlled asthma for the mother, the fetus, and the pregnancy.

About 12% of women of childbearing age have asthma. It is the most common chronic condition in pregnant women. Pregnancy affects asthma, and vice versa. Due to mechanical, hormonal, and immunological changes, allergic conditions, including asthma, can worsen.

First, pregnancy exerts mechanical pressure on respiratory function because of the progressive increase in uterine volume, diaphragm elevation, and various anatomical changes leading to chest expansion. The latter changes include increased subcostal angle, anteroposterior and transverse diameters, and thoracic circumference. 

Respiratory function is affected, with a decrease in functional residual capacity and expiratory reserve volume but an increase in inspiratory capacity, maximal ventilation, and tidal volume. The resulting hyperventilation manifests clinically as dyspnea, which affects up to 70% of pregnant women and can be mistaken for exacerbation symptoms.

Besides mechanical impact, hormonal changes occur during pregnancy, including elevated estrogen and progesterone levels. Placental hormones increase during the third trimester. These steroid hormones weaken the respiratory mucosa through structural changes in the bronchial wall and the activity of inflammatory cells involved in asthma, while influencing bronchial muscle tone. Estrogens have a dual effect. They are immunostimulatory at low doses and immunosuppressive at high doses (as in late pregnancy). This phenomenon suggests a role in immune tolerance toward the fetus.
 

The Rule of Thirds

Asthma progression during pregnancy is unpredictable. According to older studies, about one third of cases remain stable, one third worsen, and one third improve. In 60% of cases, the course remains similar from one pregnancy to another. Pregnancy is considered a period of asthma instability, with a doubled risk for exacerbation compared with nonpregnant women. Several pregnancy-specific factors contribute, including gastroesophageal reflux, excessive weight gain, active or passive smoking, and usual risk factors like infections. However, the main risk factor for exacerbation and loss of asthma control is insufficient maintenance treatment.

“The control of asthma during pregnancy is influenced by pregnancy itself, but especially by the severity of the disease before pregnancy and the underuse of inhaled corticosteroids,” said Mohammed Tawfik el Fassy Fihry, MD, pulmonologist at Ibn Sina Souissi Hospital in Rabat, Morocco. “This treatment insufficiency is the main cause of poor asthma control and sometimes of severe exacerbations.”
 

Inhaled Corticosteroid Often Insufficient

A 2017 study conducted in France found that one third of women had their asthma treatment reduced in the first trimester of pregnancy. Another observation was the frequent replacement of fixed combinations (such as long- and short-acting bronchodilators and inhaled corticosteroids) with simple inhaled corticosteroid therapy.

“A significant proportion of pregnant women on maintenance therapy decide to stop it as soon as they discover their pregnancy,” said Chantal Raherison-Semjen, PhD, coordinator of the Women and Lung group of the French Society of Pulmonology (SPLF) and of the pulmonology department at the University Hospital of Pointe-à-Pitre in Guadeloupe, France. “Treating physicians also often opt for therapeutic de-escalation, which involves stopping long-acting bronchodilators in favor of only inhaled corticosteroid therapy, which is usually insufficient for optimal asthma control.”

In severe exacerbations, especially during the first trimester of pregnancy, poorly controlled asthma can lead to complications in fetal development, such as low birth weight, intrauterine growth retardation, prematurity, and congenital malformations.

It can also affect maternal health by increasing the risk for gestational diabetes and affecting the course of pregnancy itself, favoring the occurrence of preeclampsia, placenta previa, placental abruption, premature rupture of membranes, spontaneous miscarriage, cesarean section, and hemorrhagic complications before and after delivery.

“When a pregnant woman presents to the emergency room due to an asthma exacerbation, physicians are often reluctant to administer optimal treatment for fear of the effects of bronchodilators and systemic corticosteroids,” said Dr. Raherison-Semjen. “As a result, these women generally receive less effective treatment in such situations, compared with nonpregnant women. This is despite the risk that severe asthma exacerbations pose to the mother and her child.”
 

‘Pregnant Woman’ Pictogram

In France, manufacturers of teratogenic or fetotoxic drugs are required to display a pictogram on the label indicating the danger for pregnant women or the fetus. The guidelines for this labeling are left to the discretion of the laboratories, however, which sometimes leads to unjustified warnings on the packaging of inhaled corticosteroids or emergency treatments. French medical societies were not consulted on this matter, which complicates prescriptions for pregnant asthmatic women, said Dr. Raherison-Semjen. The SPLF condemns the harmful effects of this decision.

Corticosteroids and Omalizumab

“Given the low, if any, risks associated with the main asthma treatments for the mother and fetus, continuing treatments started before conception is highly recommended,” said Dr. Raherison-Semjen. Inhaled corticosteroids, the cornerstone of asthma treatment, are the primary therapy, and the dosage can be adjusted as strictly necessary. “When properly managed, treatment generally allows for asthma control and reduces the risk for complications during pregnancy to the same level observed in the general population.”

Depending on asthma control levels, long-acting beta-2 agonists (eg, formoterol, salmeterol, and indacaterol) can be added, and possibly leukotriene antagonists. Before pregnancy, prescribed medications should be continued, including biologics prescribed for severe asthma. The exception is omalizumab, which can be started during pregnancy without risk.

For its part, allergen immunotherapy should also be maintained but without dose increases. Oral corticosteroids are reserved for severe exacerbations.

As specified by the GINA report of 2023, the benefits of active asthma treatment during pregnancy far outweigh the risks of usual asthma medications (Level A). This view is supported by reassuring data from the Reference Center for Teratogenic Agents. “There is no scientific-medical evidence justifying that pregnant women with asthma should not be treated the same way as when they are not pregnant,” said Dr. Raherison-Semjen.
 

Useful Links

The Asthma Control Test is a quick questionnaire that allows practitioners to ensure their patient›s asthma control. A score below 20 of 25 indicates poor asthma control. It has been specifically validated for pregnancy.

Dr. Tawfik el Fassy Fihry reported having no relevant financial relationships. Dr. Raherison-Semjen reported receiving compensation from AstraZeneca, B. Ingelheim, ALK, Novartis, Banook, GSK, and Mundi Pharma.

This story was translated from the Medscape French edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

PARIS — Pregnancy is a period of asthma instability; it entails an increased risk for exacerbations. While therapeutic de-escalation, if not the outright cessation of maintenance treatment, is common, experts used the 19th Francophone Congress of Allergology to emphasize the importance of well-controlled asthma for the mother, the fetus, and the pregnancy.

About 12% of women of childbearing age have asthma. It is the most common chronic condition in pregnant women. Pregnancy affects asthma, and vice versa. Due to mechanical, hormonal, and immunological changes, allergic conditions, including asthma, can worsen.

First, pregnancy exerts mechanical pressure on respiratory function because of the progressive increase in uterine volume, diaphragm elevation, and various anatomical changes leading to chest expansion. The latter changes include increased subcostal angle, anteroposterior and transverse diameters, and thoracic circumference. 

Respiratory function is affected, with a decrease in functional residual capacity and expiratory reserve volume but an increase in inspiratory capacity, maximal ventilation, and tidal volume. The resulting hyperventilation manifests clinically as dyspnea, which affects up to 70% of pregnant women and can be mistaken for exacerbation symptoms.

Besides mechanical impact, hormonal changes occur during pregnancy, including elevated estrogen and progesterone levels. Placental hormones increase during the third trimester. These steroid hormones weaken the respiratory mucosa through structural changes in the bronchial wall and the activity of inflammatory cells involved in asthma, while influencing bronchial muscle tone. Estrogens have a dual effect. They are immunostimulatory at low doses and immunosuppressive at high doses (as in late pregnancy). This phenomenon suggests a role in immune tolerance toward the fetus.
 

The Rule of Thirds

Asthma progression during pregnancy is unpredictable. According to older studies, about one third of cases remain stable, one third worsen, and one third improve. In 60% of cases, the course remains similar from one pregnancy to another. Pregnancy is considered a period of asthma instability, with a doubled risk for exacerbation compared with nonpregnant women. Several pregnancy-specific factors contribute, including gastroesophageal reflux, excessive weight gain, active or passive smoking, and usual risk factors like infections. However, the main risk factor for exacerbation and loss of asthma control is insufficient maintenance treatment.

“The control of asthma during pregnancy is influenced by pregnancy itself, but especially by the severity of the disease before pregnancy and the underuse of inhaled corticosteroids,” said Mohammed Tawfik el Fassy Fihry, MD, pulmonologist at Ibn Sina Souissi Hospital in Rabat, Morocco. “This treatment insufficiency is the main cause of poor asthma control and sometimes of severe exacerbations.”
 

Inhaled Corticosteroid Often Insufficient

A 2017 study conducted in France found that one third of women had their asthma treatment reduced in the first trimester of pregnancy. Another observation was the frequent replacement of fixed combinations (such as long- and short-acting bronchodilators and inhaled corticosteroids) with simple inhaled corticosteroid therapy.

“A significant proportion of pregnant women on maintenance therapy decide to stop it as soon as they discover their pregnancy,” said Chantal Raherison-Semjen, PhD, coordinator of the Women and Lung group of the French Society of Pulmonology (SPLF) and of the pulmonology department at the University Hospital of Pointe-à-Pitre in Guadeloupe, France. “Treating physicians also often opt for therapeutic de-escalation, which involves stopping long-acting bronchodilators in favor of only inhaled corticosteroid therapy, which is usually insufficient for optimal asthma control.”

In severe exacerbations, especially during the first trimester of pregnancy, poorly controlled asthma can lead to complications in fetal development, such as low birth weight, intrauterine growth retardation, prematurity, and congenital malformations.

It can also affect maternal health by increasing the risk for gestational diabetes and affecting the course of pregnancy itself, favoring the occurrence of preeclampsia, placenta previa, placental abruption, premature rupture of membranes, spontaneous miscarriage, cesarean section, and hemorrhagic complications before and after delivery.

“When a pregnant woman presents to the emergency room due to an asthma exacerbation, physicians are often reluctant to administer optimal treatment for fear of the effects of bronchodilators and systemic corticosteroids,” said Dr. Raherison-Semjen. “As a result, these women generally receive less effective treatment in such situations, compared with nonpregnant women. This is despite the risk that severe asthma exacerbations pose to the mother and her child.”
 

‘Pregnant Woman’ Pictogram

In France, manufacturers of teratogenic or fetotoxic drugs are required to display a pictogram on the label indicating the danger for pregnant women or the fetus. The guidelines for this labeling are left to the discretion of the laboratories, however, which sometimes leads to unjustified warnings on the packaging of inhaled corticosteroids or emergency treatments. French medical societies were not consulted on this matter, which complicates prescriptions for pregnant asthmatic women, said Dr. Raherison-Semjen. The SPLF condemns the harmful effects of this decision.

Corticosteroids and Omalizumab

“Given the low, if any, risks associated with the main asthma treatments for the mother and fetus, continuing treatments started before conception is highly recommended,” said Dr. Raherison-Semjen. Inhaled corticosteroids, the cornerstone of asthma treatment, are the primary therapy, and the dosage can be adjusted as strictly necessary. “When properly managed, treatment generally allows for asthma control and reduces the risk for complications during pregnancy to the same level observed in the general population.”

Depending on asthma control levels, long-acting beta-2 agonists (eg, formoterol, salmeterol, and indacaterol) can be added, and possibly leukotriene antagonists. Before pregnancy, prescribed medications should be continued, including biologics prescribed for severe asthma. The exception is omalizumab, which can be started during pregnancy without risk.

For its part, allergen immunotherapy should also be maintained but without dose increases. Oral corticosteroids are reserved for severe exacerbations.

As specified by the GINA report of 2023, the benefits of active asthma treatment during pregnancy far outweigh the risks of usual asthma medications (Level A). This view is supported by reassuring data from the Reference Center for Teratogenic Agents. “There is no scientific-medical evidence justifying that pregnant women with asthma should not be treated the same way as when they are not pregnant,” said Dr. Raherison-Semjen.
 

Useful Links

The Asthma Control Test is a quick questionnaire that allows practitioners to ensure their patient›s asthma control. A score below 20 of 25 indicates poor asthma control. It has been specifically validated for pregnancy.

Dr. Tawfik el Fassy Fihry reported having no relevant financial relationships. Dr. Raherison-Semjen reported receiving compensation from AstraZeneca, B. Ingelheim, ALK, Novartis, Banook, GSK, and Mundi Pharma.

This story was translated from the Medscape French edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

PARIS — Pregnancy is a period of asthma instability; it entails an increased risk for exacerbations. While therapeutic de-escalation, if not the outright cessation of maintenance treatment, is common, experts used the 19th Francophone Congress of Allergology to emphasize the importance of well-controlled asthma for the mother, the fetus, and the pregnancy.

About 12% of women of childbearing age have asthma. It is the most common chronic condition in pregnant women. Pregnancy affects asthma, and vice versa. Due to mechanical, hormonal, and immunological changes, allergic conditions, including asthma, can worsen.

First, pregnancy exerts mechanical pressure on respiratory function because of the progressive increase in uterine volume, diaphragm elevation, and various anatomical changes leading to chest expansion. The latter changes include increased subcostal angle, anteroposterior and transverse diameters, and thoracic circumference. 

Respiratory function is affected, with a decrease in functional residual capacity and expiratory reserve volume but an increase in inspiratory capacity, maximal ventilation, and tidal volume. The resulting hyperventilation manifests clinically as dyspnea, which affects up to 70% of pregnant women and can be mistaken for exacerbation symptoms.

Besides mechanical impact, hormonal changes occur during pregnancy, including elevated estrogen and progesterone levels. Placental hormones increase during the third trimester. These steroid hormones weaken the respiratory mucosa through structural changes in the bronchial wall and the activity of inflammatory cells involved in asthma, while influencing bronchial muscle tone. Estrogens have a dual effect. They are immunostimulatory at low doses and immunosuppressive at high doses (as in late pregnancy). This phenomenon suggests a role in immune tolerance toward the fetus.
 

The Rule of Thirds

Asthma progression during pregnancy is unpredictable. According to older studies, about one third of cases remain stable, one third worsen, and one third improve. In 60% of cases, the course remains similar from one pregnancy to another. Pregnancy is considered a period of asthma instability, with a doubled risk for exacerbation compared with nonpregnant women. Several pregnancy-specific factors contribute, including gastroesophageal reflux, excessive weight gain, active or passive smoking, and usual risk factors like infections. However, the main risk factor for exacerbation and loss of asthma control is insufficient maintenance treatment.

“The control of asthma during pregnancy is influenced by pregnancy itself, but especially by the severity of the disease before pregnancy and the underuse of inhaled corticosteroids,” said Mohammed Tawfik el Fassy Fihry, MD, pulmonologist at Ibn Sina Souissi Hospital in Rabat, Morocco. “This treatment insufficiency is the main cause of poor asthma control and sometimes of severe exacerbations.”
 

Inhaled Corticosteroid Often Insufficient

A 2017 study conducted in France found that one third of women had their asthma treatment reduced in the first trimester of pregnancy. Another observation was the frequent replacement of fixed combinations (such as long- and short-acting bronchodilators and inhaled corticosteroids) with simple inhaled corticosteroid therapy.

“A significant proportion of pregnant women on maintenance therapy decide to stop it as soon as they discover their pregnancy,” said Chantal Raherison-Semjen, PhD, coordinator of the Women and Lung group of the French Society of Pulmonology (SPLF) and of the pulmonology department at the University Hospital of Pointe-à-Pitre in Guadeloupe, France. “Treating physicians also often opt for therapeutic de-escalation, which involves stopping long-acting bronchodilators in favor of only inhaled corticosteroid therapy, which is usually insufficient for optimal asthma control.”

In severe exacerbations, especially during the first trimester of pregnancy, poorly controlled asthma can lead to complications in fetal development, such as low birth weight, intrauterine growth retardation, prematurity, and congenital malformations.

It can also affect maternal health by increasing the risk for gestational diabetes and affecting the course of pregnancy itself, favoring the occurrence of preeclampsia, placenta previa, placental abruption, premature rupture of membranes, spontaneous miscarriage, cesarean section, and hemorrhagic complications before and after delivery.

“When a pregnant woman presents to the emergency room due to an asthma exacerbation, physicians are often reluctant to administer optimal treatment for fear of the effects of bronchodilators and systemic corticosteroids,” said Dr. Raherison-Semjen. “As a result, these women generally receive less effective treatment in such situations, compared with nonpregnant women. This is despite the risk that severe asthma exacerbations pose to the mother and her child.”
 

‘Pregnant Woman’ Pictogram

In France, manufacturers of teratogenic or fetotoxic drugs are required to display a pictogram on the label indicating the danger for pregnant women or the fetus. The guidelines for this labeling are left to the discretion of the laboratories, however, which sometimes leads to unjustified warnings on the packaging of inhaled corticosteroids or emergency treatments. French medical societies were not consulted on this matter, which complicates prescriptions for pregnant asthmatic women, said Dr. Raherison-Semjen. The SPLF condemns the harmful effects of this decision.

Corticosteroids and Omalizumab

“Given the low, if any, risks associated with the main asthma treatments for the mother and fetus, continuing treatments started before conception is highly recommended,” said Dr. Raherison-Semjen. Inhaled corticosteroids, the cornerstone of asthma treatment, are the primary therapy, and the dosage can be adjusted as strictly necessary. “When properly managed, treatment generally allows for asthma control and reduces the risk for complications during pregnancy to the same level observed in the general population.”

Depending on asthma control levels, long-acting beta-2 agonists (eg, formoterol, salmeterol, and indacaterol) can be added, and possibly leukotriene antagonists. Before pregnancy, prescribed medications should be continued, including biologics prescribed for severe asthma. The exception is omalizumab, which can be started during pregnancy without risk.

For its part, allergen immunotherapy should also be maintained but without dose increases. Oral corticosteroids are reserved for severe exacerbations.

As specified by the GINA report of 2023, the benefits of active asthma treatment during pregnancy far outweigh the risks of usual asthma medications (Level A). This view is supported by reassuring data from the Reference Center for Teratogenic Agents. “There is no scientific-medical evidence justifying that pregnant women with asthma should not be treated the same way as when they are not pregnant,” said Dr. Raherison-Semjen.
 

Useful Links

The Asthma Control Test is a quick questionnaire that allows practitioners to ensure their patient›s asthma control. A score below 20 of 25 indicates poor asthma control. It has been specifically validated for pregnancy.

Dr. Tawfik el Fassy Fihry reported having no relevant financial relationships. Dr. Raherison-Semjen reported receiving compensation from AstraZeneca, B. Ingelheim, ALK, Novartis, Banook, GSK, and Mundi Pharma.

This story was translated from the Medscape French edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

A meta-analysis showed that the use of oral tranexamic acid along with the standard triple combination cream (TCC) reduces melasma severity and recurrence in patients with melasma, without increasing toxicity.

METHODOLOGY:

• Current treatments for melasma focus on inducing remission and preventing relapse. Tranexamic acid, an antifibrinolytic drug, has shown promise in recent studies, but its optimal use, either alone or as an adjunct to TCC, remains unclear.
• Researchers conducted a meta-analysis of four randomized controlled trials patients that compared oral tranexamic acid plus TCC (hydroquinone, retinoic acid, and hydrocortisone) and TCC alone in 480 patients with melasma, divided almost evenly into the two treatment groups.
• The main outcome was the change in the Melasma Severity Area Index (MASI) score and recurrence rate from baseline.

TAKEAWAY:

• Patients treated with oral tranexamic acid plus TCC showed a greater reduction in MASI scores compared with those who received TCC alone (mean difference, −3.10; P = .03).
• The recurrence rate of melasma was significantly lower in the tranexamic acid plus TCC group (risk ratio [RR], 0.28; P < .001).
• There was no significant difference in the incidences of erythema (RR, 0.63; P = .147) and burning (RR, 0.59; P = .131).

IN PRACTICE:

“Evidence indicates that oral tranexamic acid confers clinical benefits, contributing to the enhancement of treatment outcomes in melasma when used in conjunction with TCC therapy,” and results are promising with regards to minimizing recurrence, the authors concluded.

SOURCE:

The study was led by Ocílio Ribeiro Gonçalves, MS, of the Federal University of Piauí, Teresina, Brazil, and was published online on June 8, 2024, in Clinical and Experimental Dermatology.

LIMITATIONS:

There was heterogeneity across studies, including different methods of administration, treatment protocols (including dosage), and timing of treatment.

DISCLOSURES:

The study reported receiving no funding. The authors declared no conflicts of interest.
 

A version of this article appeared on Medscape.com.

TOPLINE:

A meta-analysis showed that the use of oral tranexamic acid along with the standard triple combination cream (TCC) reduces melasma severity and recurrence in patients with melasma, without increasing toxicity.

METHODOLOGY:

• Current treatments for melasma focus on inducing remission and preventing relapse. Tranexamic acid, an antifibrinolytic drug, has shown promise in recent studies, but its optimal use, either alone or as an adjunct to TCC, remains unclear.
• Researchers conducted a meta-analysis of four randomized controlled trials patients that compared oral tranexamic acid plus TCC (hydroquinone, retinoic acid, and hydrocortisone) and TCC alone in 480 patients with melasma, divided almost evenly into the two treatment groups.
• The main outcome was the change in the Melasma Severity Area Index (MASI) score and recurrence rate from baseline.

TAKEAWAY:

• Patients treated with oral tranexamic acid plus TCC showed a greater reduction in MASI scores compared with those who received TCC alone (mean difference, −3.10; P = .03).
• The recurrence rate of melasma was significantly lower in the tranexamic acid plus TCC group (risk ratio [RR], 0.28; P < .001).
• There was no significant difference in the incidences of erythema (RR, 0.63; P = .147) and burning (RR, 0.59; P = .131).

IN PRACTICE:

“Evidence indicates that oral tranexamic acid confers clinical benefits, contributing to the enhancement of treatment outcomes in melasma when used in conjunction with TCC therapy,” and results are promising with regards to minimizing recurrence, the authors concluded.

SOURCE:

The study was led by Ocílio Ribeiro Gonçalves, MS, of the Federal University of Piauí, Teresina, Brazil, and was published online on June 8, 2024, in Clinical and Experimental Dermatology.

LIMITATIONS:

There was heterogeneity across studies, including different methods of administration, treatment protocols (including dosage), and timing of treatment.

DISCLOSURES:

The study reported receiving no funding. The authors declared no conflicts of interest.
 

A version of this article appeared on Medscape.com.

TOPLINE:

A meta-analysis showed that the use of oral tranexamic acid along with the standard triple combination cream (TCC) reduces melasma severity and recurrence in patients with melasma, without increasing toxicity.

METHODOLOGY:

• Current treatments for melasma focus on inducing remission and preventing relapse. Tranexamic acid, an antifibrinolytic drug, has shown promise in recent studies, but its optimal use, either alone or as an adjunct to TCC, remains unclear.
• Researchers conducted a meta-analysis of four randomized controlled trials patients that compared oral tranexamic acid plus TCC (hydroquinone, retinoic acid, and hydrocortisone) and TCC alone in 480 patients with melasma, divided almost evenly into the two treatment groups.
• The main outcome was the change in the Melasma Severity Area Index (MASI) score and recurrence rate from baseline.

TAKEAWAY:

• Patients treated with oral tranexamic acid plus TCC showed a greater reduction in MASI scores compared with those who received TCC alone (mean difference, −3.10; P = .03).
• The recurrence rate of melasma was significantly lower in the tranexamic acid plus TCC group (risk ratio [RR], 0.28; P < .001).
• There was no significant difference in the incidences of erythema (RR, 0.63; P = .147) and burning (RR, 0.59; P = .131).

IN PRACTICE:

“Evidence indicates that oral tranexamic acid confers clinical benefits, contributing to the enhancement of treatment outcomes in melasma when used in conjunction with TCC therapy,” and results are promising with regards to minimizing recurrence, the authors concluded.

SOURCE:

The study was led by Ocílio Ribeiro Gonçalves, MS, of the Federal University of Piauí, Teresina, Brazil, and was published online on June 8, 2024, in Clinical and Experimental Dermatology.

LIMITATIONS:

There was heterogeneity across studies, including different methods of administration, treatment protocols (including dosage), and timing of treatment.

DISCLOSURES:

The study reported receiving no funding. The authors declared no conflicts of interest.
 

A version of this article appeared on Medscape.com.

In the wake of a debilitating cyberattack against one of the nation’s largest health care systems, Marvin Ruckle, a nurse at an Ascension hospital in Wichita, Kansas, said he had a frightening experience: He nearly gave a baby “the wrong dose of narcotic” because of confusing paperwork.

Ruckle, who has worked in the neonatal intensive care unit at Ascension Via Christi St. Joseph for two decades, said it was “hard to decipher which was the correct dose” on the medication record. He’d “never seen that happen,” he said, “when we were on the computer system” before the cyberattack.

A May 8 ransomware attack against Ascension, a Catholic health system with 140 hospitals in at least 10 states, locked providers out of systems that track and coordinate nearly every aspect of patient care. They include its systems for electronic health records, some phones, and ones “utilized to order certain tests, procedures and medications,” the company said in a May 9 statement.

More than a dozen doctors and nurses who work for the sprawling health system told Michigan Public and KFF Health News that patient care at its hospitals across the nation was compromised in the fallout of the cyberattack over the past several weeks. Clinicians working for hospitals in three states described harrowing lapses, including delayed or lost lab results, medication errors, and an absence of routine safety checks via technology to prevent potentially fatal mistakes.

Despite a precipitous rise in cyberattacks against the health sector in recent years, a weeks-long disruption of this magnitude is beyond what most health systems are prepared for, said John S. Clark, an associate chief pharmacy officer at the University of Michigan health system.

“I don’t believe that anyone is fully prepared,” he said. Most emergency management plans “are designed around long-term downtimes that are into one, two, or three days.”

Ascension in a public statement May 9 said its care teams were “trained for these kinds of disruptions,” but did not respond to questions in early June about whether it had prepared for longer periods of downtime. Ascension said June 14 it had restored access to electronic health records across its network, but that patient “medical records and other information collected between May 8” and when the service was restored “may be temporarily inaccessible as we work to update the portal with information collected during the system downtime.”

Ruckle said he “had no training” for the cyberattack.
 

Back to Paper

Lisa Watson, an intensive care unit nurse at Ascension Via Christi St. Francis hospital in Wichita, described her own close call. She said she nearly administered the wrong medication to a critically ill patient because she couldn’t scan it as she normally would. “My patient probably would have passed away had I not caught it,” she said.

Watson is no stranger to using paper for patients’ medical charts, saying she did so “for probably half of my career,” before electronic health records became ubiquitous in hospitals. What happened after the cyberattack was “by no means the same.”

“When we paper-charted, we had systems in place to get those orders to other departments in a timely manner,” she said, “and those have all gone away.”

Melissa LaRue, an ICU nurse at Ascension Saint Agnes Hospital in Baltimore, described a close call with “administering the wrong dosage” of a patient’s blood pressure medication. “Luckily,” she said, it was “triple-checked and remedied before that could happen. But I think the potential for harm is there when you have so much information and paperwork that you have to go through.”

Clinicians say their hospitals have relied on slapdash workarounds, using handwritten notes, faxes, sticky notes, and basic computer spreadsheets — many devised on the fly by doctors and nurses — to care for patients.

More than a dozen other nurses and doctors, some of them without union protections, at Ascension hospitals in Michigan recounted situations in which they say patient care was compromised. Those clinicians spoke on the condition that they not be named for fear of retaliation by their employer.

An Ascension hospital emergency room doctor in Detroit said a man on the city’s east side was given a dangerous narcotic intended for another patient because of a paperwork mix-up. As a result, the patient’s breathing slowed to the point that he had to be put on a ventilator. “We intubated him and we sent him to the ICU because he got the wrong medication.”

A nurse in a Michigan Ascension hospital ER said a woman with low blood sugar and “altered mental status” went into cardiac arrest and died after staff said they waited four hours for lab results they needed to determine how to treat her, but never received. “If I started having crushing chest pain in the middle of work and thought I was having a big one, I would grab someone to drive me down the street to another hospital,” the same ER nurse said.

Similar concerns reportedly led a travel nurse at an Ascension hospital in Indiana to quit. “I just want to warn those patients that are coming to any of the Ascension facilities that there will be delays in care. There is potential for error and for harm,” Justin Neisser told CBS4 in Indianapolis in May.

Several nurses and doctors at Ascension hospitals said they feared the errors they’ve witnessed since the cyberattack began could threaten their professional licenses. “This is how a RaDonda Vaught happens,” one nurse said, referring to the Tennessee nurse who was convicted of criminally negligent homicide in 2022 for a fatal drug error.

Reporters were not able to review records to verify clinicians’ claims because of privacy laws surrounding patients’ medical information that apply to health care professionals.

Ascension declined to answer questions about claims that care has been affected by the ransomware attack. “As we have made clear throughout this cyber attack which has impacted our system and our dedicated clinical providers, caring for our patients is our highest priority,” Sean Fitzpatrick, Ascension’s vice president of external communications, said via email on June 3. “We are confident that our care providers in our hospitals and facilities continue to provide quality medical care.”

The federal government requires hospitals to protect patients’ sensitive health data, according to cybersecurity experts. However, there are no federal requirements for hospitals to prevent or prepare for cyberattacks that could compromise their electronic systems.
 

Hospitals: ‘The No.1 Target of Ransomware’

“We’ve started to think about these as public health issues and disasters on the scale of earthquakes or hurricanes,” said Jeff Tully, a co-director of the Center for Healthcare Cybersecurity at the University of California-San Diego. “These types of cybersecurity incidents should be thought of as a matter of when, and not if.”

Josh Corman, a cybersecurity expert and advocate, said ransom crews regard hospitals as the perfect prey: “They have terrible security and they’ll pay. So almost immediately, hospitals went to the No. 1 target of ransomware.”

In 2023, the health sector experienced the largest share of ransomware attacks of 16 infrastructure sectors considered vital to national security or safety, according to an FBI report on internet crimes. In March, the federal Department of Health and Human Services said reported large breaches involving ransomware had jumped by 264% over the past five years.

A cyberattack this year on Change Healthcare, a unit of UnitedHealth Group’s Optum division that processes billions of health care transactions every year, crippled the business of providers, pharmacies, and hospitals.

In May, UnitedHealth Group CEO Andrew Witty told lawmakers the company paid a $22 million ransom as a result of the Change Healthcare attack — which occurred after hackers accessed a company portal that didn’t have multifactor authentication, a basic cybersecurity tool.

The Biden administration in recent months has pushed to bolster health care cybersecurity standards, but it’s not clear which new measures will be required.

In January, HHS nudged companies to improve email security, add multifactor authentication, and institute cybersecurity training and testing, among other voluntary measures. The Centers for Medicare & Medicaid Services is expected to release new requirements for hospitals, but the scope and timing are unclear. The same is true of an update HHS is expected to make to patient privacy regulations.

HHS said the voluntary measures “will inform the creation of new enforceable cybersecurity standards,” department spokesperson Jeff Nesbit said in a statement.

“The recent cyberattack at Ascension only underscores the need for everyone in the health care ecosystem to do their part to secure their systems and protect patients,” Nesbit said.

Meanwhile, lobbyists for the hospital industry contend cybersecurity mandates or penalties are misplaced and would curtail hospitals’ resources to fend off attacks.

“Hospitals and health systems are not the primary source of cyber risk exposure facing the health care sector,” the American Hospital Association, the largest lobbying group for U.S. hospitals, said in an April statement prepared for U.S. House lawmakers. Most large data breaches that hit hospitals in 2023 originated with third-party “business associates” or other health entities, including CMS itself, the AHA statement said.

Hospitals consolidating into large multistate health systems face increased risk of data breaches and ransomware attacks, according to one study. Ascension in 2022 was the third-largest hospital chain in the U.S. by number of beds, according to the most recent data from the federal Agency for Healthcare Research and Quality.

And while cybersecurity regulations can quickly become outdated, they can at least make it clear that if health systems fail to implement basic protections there “should be consequences for that,” Jim Bagian, a former director of the National Center for Patient Safety at the Veterans Health Administration, told Michigan Public’s Stateside.

Patients can pay the price when lapses occur. Those in hospital care face a greater likelihood of death during a cyberattack, according to researchers at the University of Minnesota School of Public Health.

Workers concerned about patient safety at Ascension hospitals in Michigan have called for the company to make changes.

“We implore Ascension to recognize the internal problems that continue to plague its hospitals, both publicly and transparently,” said Dina Carlisle, a nurse and the president of the OPEIU Local 40 union, which represents nurses at Ascension Providence Rochester. At least 125 staff members at that Ascension hospital have signed a petition asking administrators to temporarily reduce elective surgeries and nonemergency patient admissions, like under the protocols many hospitals adopted early in the covid-19 pandemic.

Watson, the Kansas ICU nurse, said in late May that nurses had urged management to bring in more nurses to help manage the workflow. “Everything that we say has fallen on deaf ears,” she said.

“It is very hard to be a nurse at Ascension right now,” Watson said in late May. “It is very hard to be a patient at Ascension right now.”

If you’re a patient or worker at an Ascension hospital and would like to tell KFF Health News about your experiences, click here to share your story with us.
 

KFF Health News is a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF—an independent source of health policy research, polling, and journalism. Learn more about KFF.

In the wake of a debilitating cyberattack against one of the nation’s largest health care systems, Marvin Ruckle, a nurse at an Ascension hospital in Wichita, Kansas, said he had a frightening experience: He nearly gave a baby “the wrong dose of narcotic” because of confusing paperwork.

Ruckle, who has worked in the neonatal intensive care unit at Ascension Via Christi St. Joseph for two decades, said it was “hard to decipher which was the correct dose” on the medication record. He’d “never seen that happen,” he said, “when we were on the computer system” before the cyberattack.

A May 8 ransomware attack against Ascension, a Catholic health system with 140 hospitals in at least 10 states, locked providers out of systems that track and coordinate nearly every aspect of patient care. They include its systems for electronic health records, some phones, and ones “utilized to order certain tests, procedures and medications,” the company said in a May 9 statement.

More than a dozen doctors and nurses who work for the sprawling health system told Michigan Public and KFF Health News that patient care at its hospitals across the nation was compromised in the fallout of the cyberattack over the past several weeks. Clinicians working for hospitals in three states described harrowing lapses, including delayed or lost lab results, medication errors, and an absence of routine safety checks via technology to prevent potentially fatal mistakes.

Despite a precipitous rise in cyberattacks against the health sector in recent years, a weeks-long disruption of this magnitude is beyond what most health systems are prepared for, said John S. Clark, an associate chief pharmacy officer at the University of Michigan health system.

“I don’t believe that anyone is fully prepared,” he said. Most emergency management plans “are designed around long-term downtimes that are into one, two, or three days.”

Ascension in a public statement May 9 said its care teams were “trained for these kinds of disruptions,” but did not respond to questions in early June about whether it had prepared for longer periods of downtime. Ascension said June 14 it had restored access to electronic health records across its network, but that patient “medical records and other information collected between May 8” and when the service was restored “may be temporarily inaccessible as we work to update the portal with information collected during the system downtime.”

Ruckle said he “had no training” for the cyberattack.
 

Back to Paper

Lisa Watson, an intensive care unit nurse at Ascension Via Christi St. Francis hospital in Wichita, described her own close call. She said she nearly administered the wrong medication to a critically ill patient because she couldn’t scan it as she normally would. “My patient probably would have passed away had I not caught it,” she said.

Watson is no stranger to using paper for patients’ medical charts, saying she did so “for probably half of my career,” before electronic health records became ubiquitous in hospitals. What happened after the cyberattack was “by no means the same.”

“When we paper-charted, we had systems in place to get those orders to other departments in a timely manner,” she said, “and those have all gone away.”

Melissa LaRue, an ICU nurse at Ascension Saint Agnes Hospital in Baltimore, described a close call with “administering the wrong dosage” of a patient’s blood pressure medication. “Luckily,” she said, it was “triple-checked and remedied before that could happen. But I think the potential for harm is there when you have so much information and paperwork that you have to go through.”

Clinicians say their hospitals have relied on slapdash workarounds, using handwritten notes, faxes, sticky notes, and basic computer spreadsheets — many devised on the fly by doctors and nurses — to care for patients.

More than a dozen other nurses and doctors, some of them without union protections, at Ascension hospitals in Michigan recounted situations in which they say patient care was compromised. Those clinicians spoke on the condition that they not be named for fear of retaliation by their employer.

An Ascension hospital emergency room doctor in Detroit said a man on the city’s east side was given a dangerous narcotic intended for another patient because of a paperwork mix-up. As a result, the patient’s breathing slowed to the point that he had to be put on a ventilator. “We intubated him and we sent him to the ICU because he got the wrong medication.”

A nurse in a Michigan Ascension hospital ER said a woman with low blood sugar and “altered mental status” went into cardiac arrest and died after staff said they waited four hours for lab results they needed to determine how to treat her, but never received. “If I started having crushing chest pain in the middle of work and thought I was having a big one, I would grab someone to drive me down the street to another hospital,” the same ER nurse said.

Similar concerns reportedly led a travel nurse at an Ascension hospital in Indiana to quit. “I just want to warn those patients that are coming to any of the Ascension facilities that there will be delays in care. There is potential for error and for harm,” Justin Neisser told CBS4 in Indianapolis in May.

Several nurses and doctors at Ascension hospitals said they feared the errors they’ve witnessed since the cyberattack began could threaten their professional licenses. “This is how a RaDonda Vaught happens,” one nurse said, referring to the Tennessee nurse who was convicted of criminally negligent homicide in 2022 for a fatal drug error.

Reporters were not able to review records to verify clinicians’ claims because of privacy laws surrounding patients’ medical information that apply to health care professionals.

Ascension declined to answer questions about claims that care has been affected by the ransomware attack. “As we have made clear throughout this cyber attack which has impacted our system and our dedicated clinical providers, caring for our patients is our highest priority,” Sean Fitzpatrick, Ascension’s vice president of external communications, said via email on June 3. “We are confident that our care providers in our hospitals and facilities continue to provide quality medical care.”

The federal government requires hospitals to protect patients’ sensitive health data, according to cybersecurity experts. However, there are no federal requirements for hospitals to prevent or prepare for cyberattacks that could compromise their electronic systems.
 

Hospitals: ‘The No.1 Target of Ransomware’

“We’ve started to think about these as public health issues and disasters on the scale of earthquakes or hurricanes,” said Jeff Tully, a co-director of the Center for Healthcare Cybersecurity at the University of California-San Diego. “These types of cybersecurity incidents should be thought of as a matter of when, and not if.”

Josh Corman, a cybersecurity expert and advocate, said ransom crews regard hospitals as the perfect prey: “They have terrible security and they’ll pay. So almost immediately, hospitals went to the No. 1 target of ransomware.”

In 2023, the health sector experienced the largest share of ransomware attacks of 16 infrastructure sectors considered vital to national security or safety, according to an FBI report on internet crimes. In March, the federal Department of Health and Human Services said reported large breaches involving ransomware had jumped by 264% over the past five years.

A cyberattack this year on Change Healthcare, a unit of UnitedHealth Group’s Optum division that processes billions of health care transactions every year, crippled the business of providers, pharmacies, and hospitals.

In May, UnitedHealth Group CEO Andrew Witty told lawmakers the company paid a $22 million ransom as a result of the Change Healthcare attack — which occurred after hackers accessed a company portal that didn’t have multifactor authentication, a basic cybersecurity tool.

The Biden administration in recent months has pushed to bolster health care cybersecurity standards, but it’s not clear which new measures will be required.

In January, HHS nudged companies to improve email security, add multifactor authentication, and institute cybersecurity training and testing, among other voluntary measures. The Centers for Medicare & Medicaid Services is expected to release new requirements for hospitals, but the scope and timing are unclear. The same is true of an update HHS is expected to make to patient privacy regulations.

HHS said the voluntary measures “will inform the creation of new enforceable cybersecurity standards,” department spokesperson Jeff Nesbit said in a statement.

“The recent cyberattack at Ascension only underscores the need for everyone in the health care ecosystem to do their part to secure their systems and protect patients,” Nesbit said.

Meanwhile, lobbyists for the hospital industry contend cybersecurity mandates or penalties are misplaced and would curtail hospitals’ resources to fend off attacks.

“Hospitals and health systems are not the primary source of cyber risk exposure facing the health care sector,” the American Hospital Association, the largest lobbying group for U.S. hospitals, said in an April statement prepared for U.S. House lawmakers. Most large data breaches that hit hospitals in 2023 originated with third-party “business associates” or other health entities, including CMS itself, the AHA statement said.

Hospitals consolidating into large multistate health systems face increased risk of data breaches and ransomware attacks, according to one study. Ascension in 2022 was the third-largest hospital chain in the U.S. by number of beds, according to the most recent data from the federal Agency for Healthcare Research and Quality.

And while cybersecurity regulations can quickly become outdated, they can at least make it clear that if health systems fail to implement basic protections there “should be consequences for that,” Jim Bagian, a former director of the National Center for Patient Safety at the Veterans Health Administration, told Michigan Public’s Stateside.

Patients can pay the price when lapses occur. Those in hospital care face a greater likelihood of death during a cyberattack, according to researchers at the University of Minnesota School of Public Health.

Workers concerned about patient safety at Ascension hospitals in Michigan have called for the company to make changes.

“We implore Ascension to recognize the internal problems that continue to plague its hospitals, both publicly and transparently,” said Dina Carlisle, a nurse and the president of the OPEIU Local 40 union, which represents nurses at Ascension Providence Rochester. At least 125 staff members at that Ascension hospital have signed a petition asking administrators to temporarily reduce elective surgeries and nonemergency patient admissions, like under the protocols many hospitals adopted early in the covid-19 pandemic.

Watson, the Kansas ICU nurse, said in late May that nurses had urged management to bring in more nurses to help manage the workflow. “Everything that we say has fallen on deaf ears,” she said.

“It is very hard to be a nurse at Ascension right now,” Watson said in late May. “It is very hard to be a patient at Ascension right now.”

If you’re a patient or worker at an Ascension hospital and would like to tell KFF Health News about your experiences, click here to share your story with us.
 

KFF Health News is a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF—an independent source of health policy research, polling, and journalism. Learn more about KFF.

In the wake of a debilitating cyberattack against one of the nation’s largest health care systems, Marvin Ruckle, a nurse at an Ascension hospital in Wichita, Kansas, said he had a frightening experience: He nearly gave a baby “the wrong dose of narcotic” because of confusing paperwork.

Ruckle, who has worked in the neonatal intensive care unit at Ascension Via Christi St. Joseph for two decades, said it was “hard to decipher which was the correct dose” on the medication record. He’d “never seen that happen,” he said, “when we were on the computer system” before the cyberattack.

A May 8 ransomware attack against Ascension, a Catholic health system with 140 hospitals in at least 10 states, locked providers out of systems that track and coordinate nearly every aspect of patient care. They include its systems for electronic health records, some phones, and ones “utilized to order certain tests, procedures and medications,” the company said in a May 9 statement.

More than a dozen doctors and nurses who work for the sprawling health system told Michigan Public and KFF Health News that patient care at its hospitals across the nation was compromised in the fallout of the cyberattack over the past several weeks. Clinicians working for hospitals in three states described harrowing lapses, including delayed or lost lab results, medication errors, and an absence of routine safety checks via technology to prevent potentially fatal mistakes.

Despite a precipitous rise in cyberattacks against the health sector in recent years, a weeks-long disruption of this magnitude is beyond what most health systems are prepared for, said John S. Clark, an associate chief pharmacy officer at the University of Michigan health system.

“I don’t believe that anyone is fully prepared,” he said. Most emergency management plans “are designed around long-term downtimes that are into one, two, or three days.”

Ascension in a public statement May 9 said its care teams were “trained for these kinds of disruptions,” but did not respond to questions in early June about whether it had prepared for longer periods of downtime. Ascension said June 14 it had restored access to electronic health records across its network, but that patient “medical records and other information collected between May 8” and when the service was restored “may be temporarily inaccessible as we work to update the portal with information collected during the system downtime.”

Ruckle said he “had no training” for the cyberattack.
 

Back to Paper

Lisa Watson, an intensive care unit nurse at Ascension Via Christi St. Francis hospital in Wichita, described her own close call. She said she nearly administered the wrong medication to a critically ill patient because she couldn’t scan it as she normally would. “My patient probably would have passed away had I not caught it,” she said.

Watson is no stranger to using paper for patients’ medical charts, saying she did so “for probably half of my career,” before electronic health records became ubiquitous in hospitals. What happened after the cyberattack was “by no means the same.”

“When we paper-charted, we had systems in place to get those orders to other departments in a timely manner,” she said, “and those have all gone away.”

Melissa LaRue, an ICU nurse at Ascension Saint Agnes Hospital in Baltimore, described a close call with “administering the wrong dosage” of a patient’s blood pressure medication. “Luckily,” she said, it was “triple-checked and remedied before that could happen. But I think the potential for harm is there when you have so much information and paperwork that you have to go through.”

Clinicians say their hospitals have relied on slapdash workarounds, using handwritten notes, faxes, sticky notes, and basic computer spreadsheets — many devised on the fly by doctors and nurses — to care for patients.

More than a dozen other nurses and doctors, some of them without union protections, at Ascension hospitals in Michigan recounted situations in which they say patient care was compromised. Those clinicians spoke on the condition that they not be named for fear of retaliation by their employer.

An Ascension hospital emergency room doctor in Detroit said a man on the city’s east side was given a dangerous narcotic intended for another patient because of a paperwork mix-up. As a result, the patient’s breathing slowed to the point that he had to be put on a ventilator. “We intubated him and we sent him to the ICU because he got the wrong medication.”

A nurse in a Michigan Ascension hospital ER said a woman with low blood sugar and “altered mental status” went into cardiac arrest and died after staff said they waited four hours for lab results they needed to determine how to treat her, but never received. “If I started having crushing chest pain in the middle of work and thought I was having a big one, I would grab someone to drive me down the street to another hospital,” the same ER nurse said.

Similar concerns reportedly led a travel nurse at an Ascension hospital in Indiana to quit. “I just want to warn those patients that are coming to any of the Ascension facilities that there will be delays in care. There is potential for error and for harm,” Justin Neisser told CBS4 in Indianapolis in May.

Several nurses and doctors at Ascension hospitals said they feared the errors they’ve witnessed since the cyberattack began could threaten their professional licenses. “This is how a RaDonda Vaught happens,” one nurse said, referring to the Tennessee nurse who was convicted of criminally negligent homicide in 2022 for a fatal drug error.

Reporters were not able to review records to verify clinicians’ claims because of privacy laws surrounding patients’ medical information that apply to health care professionals.

Ascension declined to answer questions about claims that care has been affected by the ransomware attack. “As we have made clear throughout this cyber attack which has impacted our system and our dedicated clinical providers, caring for our patients is our highest priority,” Sean Fitzpatrick, Ascension’s vice president of external communications, said via email on June 3. “We are confident that our care providers in our hospitals and facilities continue to provide quality medical care.”

The federal government requires hospitals to protect patients’ sensitive health data, according to cybersecurity experts. However, there are no federal requirements for hospitals to prevent or prepare for cyberattacks that could compromise their electronic systems.
 

Hospitals: ‘The No.1 Target of Ransomware’

“We’ve started to think about these as public health issues and disasters on the scale of earthquakes or hurricanes,” said Jeff Tully, a co-director of the Center for Healthcare Cybersecurity at the University of California-San Diego. “These types of cybersecurity incidents should be thought of as a matter of when, and not if.”

Josh Corman, a cybersecurity expert and advocate, said ransom crews regard hospitals as the perfect prey: “They have terrible security and they’ll pay. So almost immediately, hospitals went to the No. 1 target of ransomware.”

In 2023, the health sector experienced the largest share of ransomware attacks of 16 infrastructure sectors considered vital to national security or safety, according to an FBI report on internet crimes. In March, the federal Department of Health and Human Services said reported large breaches involving ransomware had jumped by 264% over the past five years.

A cyberattack this year on Change Healthcare, a unit of UnitedHealth Group’s Optum division that processes billions of health care transactions every year, crippled the business of providers, pharmacies, and hospitals.

In May, UnitedHealth Group CEO Andrew Witty told lawmakers the company paid a $22 million ransom as a result of the Change Healthcare attack — which occurred after hackers accessed a company portal that didn’t have multifactor authentication, a basic cybersecurity tool.

The Biden administration in recent months has pushed to bolster health care cybersecurity standards, but it’s not clear which new measures will be required.

In January, HHS nudged companies to improve email security, add multifactor authentication, and institute cybersecurity training and testing, among other voluntary measures. The Centers for Medicare & Medicaid Services is expected to release new requirements for hospitals, but the scope and timing are unclear. The same is true of an update HHS is expected to make to patient privacy regulations.

HHS said the voluntary measures “will inform the creation of new enforceable cybersecurity standards,” department spokesperson Jeff Nesbit said in a statement.

“The recent cyberattack at Ascension only underscores the need for everyone in the health care ecosystem to do their part to secure their systems and protect patients,” Nesbit said.

Meanwhile, lobbyists for the hospital industry contend cybersecurity mandates or penalties are misplaced and would curtail hospitals’ resources to fend off attacks.

“Hospitals and health systems are not the primary source of cyber risk exposure facing the health care sector,” the American Hospital Association, the largest lobbying group for U.S. hospitals, said in an April statement prepared for U.S. House lawmakers. Most large data breaches that hit hospitals in 2023 originated with third-party “business associates” or other health entities, including CMS itself, the AHA statement said.

Hospitals consolidating into large multistate health systems face increased risk of data breaches and ransomware attacks, according to one study. Ascension in 2022 was the third-largest hospital chain in the U.S. by number of beds, according to the most recent data from the federal Agency for Healthcare Research and Quality.

And while cybersecurity regulations can quickly become outdated, they can at least make it clear that if health systems fail to implement basic protections there “should be consequences for that,” Jim Bagian, a former director of the National Center for Patient Safety at the Veterans Health Administration, told Michigan Public’s Stateside.

Patients can pay the price when lapses occur. Those in hospital care face a greater likelihood of death during a cyberattack, according to researchers at the University of Minnesota School of Public Health.

Workers concerned about patient safety at Ascension hospitals in Michigan have called for the company to make changes.

“We implore Ascension to recognize the internal problems that continue to plague its hospitals, both publicly and transparently,” said Dina Carlisle, a nurse and the president of the OPEIU Local 40 union, which represents nurses at Ascension Providence Rochester. At least 125 staff members at that Ascension hospital have signed a petition asking administrators to temporarily reduce elective surgeries and nonemergency patient admissions, like under the protocols many hospitals adopted early in the covid-19 pandemic.

Watson, the Kansas ICU nurse, said in late May that nurses had urged management to bring in more nurses to help manage the workflow. “Everything that we say has fallen on deaf ears,” she said.

“It is very hard to be a nurse at Ascension right now,” Watson said in late May. “It is very hard to be a patient at Ascension right now.”

If you’re a patient or worker at an Ascension hospital and would like to tell KFF Health News about your experiences, click here to share your story with us.
 

KFF Health News is a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF—an independent source of health policy research, polling, and journalism. Learn more about KFF.

For decades it’s been thought that preconception use of the oral antidiabetic metformin by mothers and fathers might result in adverse fetal outcomes, including congenital malformations and stillbirths.

Women with type 2 diabetes (T2D) are often advised to switch to insulin before or during early pregnancy out of concern for fetal safety. But two studies from the Harvard T.H. Chan School of Public Health in Boston, Massachusetts — one in mothers, the other in fathers — report that metformin, a common and cost-effective antidiabetic agent, is not associated with a significant increased risk of teratogenicity and negative perinatal outcomes. The studies appear in Annals of Internal Medicine.

The studies may make it easier for physicians to reassure diabetic parents-to-be about the safety of metformin use before conception and in early pregnancy,

In the context of sparse existing safety data, the maternal analysis looked at Medicaid data on 12,489 mothers (mean age, about 30) receiving metformin for pregestational T2D during the period 2000-2018. “Many women become pregnant while still taking noninsulin oral antidiabetics, mostly metformin, and one safety concern is whether metformin could cause birth defects,” lead author Yu-Han Chiu, MD, ScD, an epidemiologist, said in an interview, commenting on the impetus for the study.

Metformin in Fathers

Turning to fathers, a much larger cohort study by Harvard T.H. Chan investigators looked at the effect of paternal metformin use and also found it to be safe.

The Harvard investigators analyzed diabetic men in 383,851 live births from 1999 to 2020 in an Israeli health fund cohort, excluding those with diabetic spouses. Across different T2D medication groups, paternal age ranged from about 35 to about 43 years. The data revealed that paternal use of metformin monotherapy in the preconception sperm production period was, after adjustment of crude numbers, not associated with major congenital malformations (MCMs) in newborns.

“While metformin has an overall good safety profile, it can lower androgen levels, and there had been some concerns that its use in fathers could alter the sperm, causing adverse effects to the fetus,” lead author and neuroepidemiologist Ran S. Rotem, MD, ScD, of the Harvard School of Public Health, Boston, Massachusetts, said in interview. “Given the increasing prevalence of diabetes in young individuals, more fathers are conceiving a child while using the medication, which could lead to a substantial population effect even if the individual risk is low. But our study suggests that the medication is safe to use by fathers before conception.”

For decades it’s been thought that preconception use of the oral antidiabetic metformin by mothers and fathers might result in adverse fetal outcomes, including congenital malformations and stillbirths.

Women with type 2 diabetes (T2D) are often advised to switch to insulin before or during early pregnancy out of concern for fetal safety. But two studies from the Harvard T.H. Chan School of Public Health in Boston, Massachusetts — one in mothers, the other in fathers — report that metformin, a common and cost-effective antidiabetic agent, is not associated with a significant increased risk of teratogenicity and negative perinatal outcomes. The studies appear in Annals of Internal Medicine.

The studies may make it easier for physicians to reassure diabetic parents-to-be about the safety of metformin use before conception and in early pregnancy,

In the context of sparse existing safety data, the maternal analysis looked at Medicaid data on 12,489 mothers (mean age, about 30) receiving metformin for pregestational T2D during the period 2000-2018. “Many women become pregnant while still taking noninsulin oral antidiabetics, mostly metformin, and one safety concern is whether metformin could cause birth defects,” lead author Yu-Han Chiu, MD, ScD, an epidemiologist, said in an interview, commenting on the impetus for the study.

Metformin in Fathers

Turning to fathers, a much larger cohort study by Harvard T.H. Chan investigators looked at the effect of paternal metformin use and also found it to be safe.

The Harvard investigators analyzed diabetic men in 383,851 live births from 1999 to 2020 in an Israeli health fund cohort, excluding those with diabetic spouses. Across different T2D medication groups, paternal age ranged from about 35 to about 43 years. The data revealed that paternal use of metformin monotherapy in the preconception sperm production period was, after adjustment of crude numbers, not associated with major congenital malformations (MCMs) in newborns.

“While metformin has an overall good safety profile, it can lower androgen levels, and there had been some concerns that its use in fathers could alter the sperm, causing adverse effects to the fetus,” lead author and neuroepidemiologist Ran S. Rotem, MD, ScD, of the Harvard School of Public Health, Boston, Massachusetts, said in interview. “Given the increasing prevalence of diabetes in young individuals, more fathers are conceiving a child while using the medication, which could lead to a substantial population effect even if the individual risk is low. But our study suggests that the medication is safe to use by fathers before conception.”

For decades it’s been thought that preconception use of the oral antidiabetic metformin by mothers and fathers might result in adverse fetal outcomes, including congenital malformations and stillbirths.

Women with type 2 diabetes (T2D) are often advised to switch to insulin before or during early pregnancy out of concern for fetal safety. But two studies from the Harvard T.H. Chan School of Public Health in Boston, Massachusetts — one in mothers, the other in fathers — report that metformin, a common and cost-effective antidiabetic agent, is not associated with a significant increased risk of teratogenicity and negative perinatal outcomes. The studies appear in Annals of Internal Medicine.

The studies may make it easier for physicians to reassure diabetic parents-to-be about the safety of metformin use before conception and in early pregnancy,

In the context of sparse existing safety data, the maternal analysis looked at Medicaid data on 12,489 mothers (mean age, about 30) receiving metformin for pregestational T2D during the period 2000-2018. “Many women become pregnant while still taking noninsulin oral antidiabetics, mostly metformin, and one safety concern is whether metformin could cause birth defects,” lead author Yu-Han Chiu, MD, ScD, an epidemiologist, said in an interview, commenting on the impetus for the study.

Metformin in Fathers

Turning to fathers, a much larger cohort study by Harvard T.H. Chan investigators looked at the effect of paternal metformin use and also found it to be safe.

The Harvard investigators analyzed diabetic men in 383,851 live births from 1999 to 2020 in an Israeli health fund cohort, excluding those with diabetic spouses. Across different T2D medication groups, paternal age ranged from about 35 to about 43 years. The data revealed that paternal use of metformin monotherapy in the preconception sperm production period was, after adjustment of crude numbers, not associated with major congenital malformations (MCMs) in newborns.

“While metformin has an overall good safety profile, it can lower androgen levels, and there had been some concerns that its use in fathers could alter the sperm, causing adverse effects to the fetus,” lead author and neuroepidemiologist Ran S. Rotem, MD, ScD, of the Harvard School of Public Health, Boston, Massachusetts, said in interview. “Given the increasing prevalence of diabetes in young individuals, more fathers are conceiving a child while using the medication, which could lead to a substantial population effect even if the individual risk is low. But our study suggests that the medication is safe to use by fathers before conception.”

Editor’s note: This is Dr. Eastern’s last “Managing Your Practice” column for Dermatology News. After his first column was published in 1986, Dr. Eastern continued writing his column monthly until the mid-1990s, resuming in 2005. In total, he has written over 300 columns on topics relevant to medical practice, ranging from hiring employees, selling and merging practices, complying with OSHA, and avoiding embezzlement, to electronic health records, burnout, medical assistants, negative online reviews, artificial intelligence in the office, and more. In the future, he will continue to provide commentary on practice issues with an occasional guest editorial.

Medicare reimbursement cuts, increasing overhead and staff salaries, and inflation have made running a profitable private practice increasingly challenging, particularly for rural and smaller offices. Medical credit cards are an increasingly popular choice to fill this gap.

Unlike a conventional credit card, a medical credit card is used only to pay for medical services.

alexialex/Getty Images

Traditionally, these cards were used to help cover procedures insurance didn’t cover — such as cosmetic procedures — but over the years, they have been expanded to cover other healthcare charges, mostly for patients who are paying out of pocket due to inadequate insurance or other reasons.

Advantages for physicians include immediate payment from the credit card company and reduced billing and collection costs. Patients are also less likely to delay or defer treatment if they can charge the payment and pay it back in installments.

The first step in offering medical credit cards is signing up with one or more third-party card companies. CareCredit is the most common provider in the medical credit card market. Other vendors include Wells Fargo, AccessOne, Alphaeon Credit, and iCare Financial. (As always, I have no financial interest in any product or service mentioned in this column.) A member of your staff signs patients up, and the credit card company checks their credit. If approved, the card company pays you your fee and assumes responsibility for collecting from the patient.

The interest charge on medical credit cards is often deferred for a period of time, typically between 6 and 24 months. If patients pay off the debt within this time, they can avoid paying interest. But, like other credit cards, if they make late payments or have an unpaid balance once the promotional period ends, they may end up with interest and fees totaling 25%-30% or more. It is important to make it very clear to your patients that payments are interest-free only if they are all made on time and within the promotional period.

According to a Consumer Financial Protection Bureau report released earlier this year, deferred interest medical credit cards or loans were used to pay nearly $23 billion in healthcare expenses from 2018 to 2020. Individuals unable to complete payment during the promotional period paid $1 billion in deferred interest payments during that period.

Despite the growing popularity of medical credit cards among physicians, it is worth noting that some consumer groups view them as predatory financial products, marketed toward people in tough financial situations. A coalition of 60 health advocacy groups has urged the Biden Administration to ban deferred interest medical credit cards. So there is that much more reason to choose candidates for medical credit cards carefully, and to make them fully aware of what obligations they are assuming.

Patients who do not think they can pay off the balance within the interest-free time frame should probably be advised to pursue an alternative payment method, such as using a conventional credit card, taking out a personal or home-equity loan, or borrowing from a retirement savings account. Some physicians are willing to negotiate a reduced fee for patients who agree to pay cash at the time of service.

Those who do choose to apply for a medical credit card should be informed of their options, which can vary considerably depending on the product and the third-party vendor. Some medical credit products can be used only for elective procedures, but some can be used more broadly for various medical expenses. Check to make sure that each patient’s financing option can be used for his or her desired medical service.

Some payment products can only be used at specific practices or groups, while others can be used at a variety of medical offices and hospitals. If a patient arrives with a medical credit card already in hand, confirm that it is one that your office accepts.

Interest rates generally vary with each card and vendor. Make patients aware of when interest rates start accruing and if the plan offers a fixed or variable APR, or if it charges compounding interest. Confirm if there is a deferred interest option, and if so, for how long.

Different medical credit products also have varying fees and payment schedules. See that each patient reads the terms of the agreement to understand when interest may start to accrue or change, as well as when certain fees may apply. Understanding when the payments are due will help them avoid additional fees, including late fees. Some medical payment plans may also have administrative or processing fees. If so, patients should be made aware of them.

Dr. Eastern practices dermatology and dermatologic surgery in Belleville, New Jersey. He is the author of numerous articles and textbook chapters, and is a longtime monthly columnist for Dermatology News. Write to him at [email protected].

Editor’s note: This is Dr. Eastern’s last “Managing Your Practice” column for Dermatology News. After his first column was published in 1986, Dr. Eastern continued writing his column monthly until the mid-1990s, resuming in 2005. In total, he has written over 300 columns on topics relevant to medical practice, ranging from hiring employees, selling and merging practices, complying with OSHA, and avoiding embezzlement, to electronic health records, burnout, medical assistants, negative online reviews, artificial intelligence in the office, and more. In the future, he will continue to provide commentary on practice issues with an occasional guest editorial.

Medicare reimbursement cuts, increasing overhead and staff salaries, and inflation have made running a profitable private practice increasingly challenging, particularly for rural and smaller offices. Medical credit cards are an increasingly popular choice to fill this gap.

Unlike a conventional credit card, a medical credit card is used only to pay for medical services.

alexialex/Getty Images

Traditionally, these cards were used to help cover procedures insurance didn’t cover — such as cosmetic procedures — but over the years, they have been expanded to cover other healthcare charges, mostly for patients who are paying out of pocket due to inadequate insurance or other reasons.

Advantages for physicians include immediate payment from the credit card company and reduced billing and collection costs. Patients are also less likely to delay or defer treatment if they can charge the payment and pay it back in installments.

The first step in offering medical credit cards is signing up with one or more third-party card companies. CareCredit is the most common provider in the medical credit card market. Other vendors include Wells Fargo, AccessOne, Alphaeon Credit, and iCare Financial. (As always, I have no financial interest in any product or service mentioned in this column.) A member of your staff signs patients up, and the credit card company checks their credit. If approved, the card company pays you your fee and assumes responsibility for collecting from the patient.

The interest charge on medical credit cards is often deferred for a period of time, typically between 6 and 24 months. If patients pay off the debt within this time, they can avoid paying interest. But, like other credit cards, if they make late payments or have an unpaid balance once the promotional period ends, they may end up with interest and fees totaling 25%-30% or more. It is important to make it very clear to your patients that payments are interest-free only if they are all made on time and within the promotional period.

According to a Consumer Financial Protection Bureau report released earlier this year, deferred interest medical credit cards or loans were used to pay nearly $23 billion in healthcare expenses from 2018 to 2020. Individuals unable to complete payment during the promotional period paid $1 billion in deferred interest payments during that period.

Despite the growing popularity of medical credit cards among physicians, it is worth noting that some consumer groups view them as predatory financial products, marketed toward people in tough financial situations. A coalition of 60 health advocacy groups has urged the Biden Administration to ban deferred interest medical credit cards. So there is that much more reason to choose candidates for medical credit cards carefully, and to make them fully aware of what obligations they are assuming.

Patients who do not think they can pay off the balance within the interest-free time frame should probably be advised to pursue an alternative payment method, such as using a conventional credit card, taking out a personal or home-equity loan, or borrowing from a retirement savings account. Some physicians are willing to negotiate a reduced fee for patients who agree to pay cash at the time of service.

Those who do choose to apply for a medical credit card should be informed of their options, which can vary considerably depending on the product and the third-party vendor. Some medical credit products can be used only for elective procedures, but some can be used more broadly for various medical expenses. Check to make sure that each patient’s financing option can be used for his or her desired medical service.

Some payment products can only be used at specific practices or groups, while others can be used at a variety of medical offices and hospitals. If a patient arrives with a medical credit card already in hand, confirm that it is one that your office accepts.

Interest rates generally vary with each card and vendor. Make patients aware of when interest rates start accruing and if the plan offers a fixed or variable APR, or if it charges compounding interest. Confirm if there is a deferred interest option, and if so, for how long.

Different medical credit products also have varying fees and payment schedules. See that each patient reads the terms of the agreement to understand when interest may start to accrue or change, as well as when certain fees may apply. Understanding when the payments are due will help them avoid additional fees, including late fees. Some medical payment plans may also have administrative or processing fees. If so, patients should be made aware of them.

Dr. Eastern practices dermatology and dermatologic surgery in Belleville, New Jersey. He is the author of numerous articles and textbook chapters, and is a longtime monthly columnist for Dermatology News. Write to him at [email protected].

Editor’s note: This is Dr. Eastern’s last “Managing Your Practice” column for Dermatology News. After his first column was published in 1986, Dr. Eastern continued writing his column monthly until the mid-1990s, resuming in 2005. In total, he has written over 300 columns on topics relevant to medical practice, ranging from hiring employees, selling and merging practices, complying with OSHA, and avoiding embezzlement, to electronic health records, burnout, medical assistants, negative online reviews, artificial intelligence in the office, and more. In the future, he will continue to provide commentary on practice issues with an occasional guest editorial.

Medicare reimbursement cuts, increasing overhead and staff salaries, and inflation have made running a profitable private practice increasingly challenging, particularly for rural and smaller offices. Medical credit cards are an increasingly popular choice to fill this gap.

Unlike a conventional credit card, a medical credit card is used only to pay for medical services.

alexialex/Getty Images

Traditionally, these cards were used to help cover procedures insurance didn’t cover — such as cosmetic procedures — but over the years, they have been expanded to cover other healthcare charges, mostly for patients who are paying out of pocket due to inadequate insurance or other reasons.

Advantages for physicians include immediate payment from the credit card company and reduced billing and collection costs. Patients are also less likely to delay or defer treatment if they can charge the payment and pay it back in installments.

The first step in offering medical credit cards is signing up with one or more third-party card companies. CareCredit is the most common provider in the medical credit card market. Other vendors include Wells Fargo, AccessOne, Alphaeon Credit, and iCare Financial. (As always, I have no financial interest in any product or service mentioned in this column.) A member of your staff signs patients up, and the credit card company checks their credit. If approved, the card company pays you your fee and assumes responsibility for collecting from the patient.

The interest charge on medical credit cards is often deferred for a period of time, typically between 6 and 24 months. If patients pay off the debt within this time, they can avoid paying interest. But, like other credit cards, if they make late payments or have an unpaid balance once the promotional period ends, they may end up with interest and fees totaling 25%-30% or more. It is important to make it very clear to your patients that payments are interest-free only if they are all made on time and within the promotional period.

According to a Consumer Financial Protection Bureau report released earlier this year, deferred interest medical credit cards or loans were used to pay nearly $23 billion in healthcare expenses from 2018 to 2020. Individuals unable to complete payment during the promotional period paid $1 billion in deferred interest payments during that period.

Despite the growing popularity of medical credit cards among physicians, it is worth noting that some consumer groups view them as predatory financial products, marketed toward people in tough financial situations. A coalition of 60 health advocacy groups has urged the Biden Administration to ban deferred interest medical credit cards. So there is that much more reason to choose candidates for medical credit cards carefully, and to make them fully aware of what obligations they are assuming.

Patients who do not think they can pay off the balance within the interest-free time frame should probably be advised to pursue an alternative payment method, such as using a conventional credit card, taking out a personal or home-equity loan, or borrowing from a retirement savings account. Some physicians are willing to negotiate a reduced fee for patients who agree to pay cash at the time of service.

Those who do choose to apply for a medical credit card should be informed of their options, which can vary considerably depending on the product and the third-party vendor. Some medical credit products can be used only for elective procedures, but some can be used more broadly for various medical expenses. Check to make sure that each patient’s financing option can be used for his or her desired medical service.

Some payment products can only be used at specific practices or groups, while others can be used at a variety of medical offices and hospitals. If a patient arrives with a medical credit card already in hand, confirm that it is one that your office accepts.

Interest rates generally vary with each card and vendor. Make patients aware of when interest rates start accruing and if the plan offers a fixed or variable APR, or if it charges compounding interest. Confirm if there is a deferred interest option, and if so, for how long.

Different medical credit products also have varying fees and payment schedules. See that each patient reads the terms of the agreement to understand when interest may start to accrue or change, as well as when certain fees may apply. Understanding when the payments are due will help them avoid additional fees, including late fees. Some medical payment plans may also have administrative or processing fees. If so, patients should be made aware of them.

Dr. Eastern practices dermatology and dermatologic surgery in Belleville, New Jersey. He is the author of numerous articles and textbook chapters, and is a longtime monthly columnist for Dermatology News. Write to him at [email protected].

The experimental drug inavolisib showed sustained benefit combined with standard treatment in advanced, PIK3CA-mutated, hormone receptor–positive, human epidermal growth factor receptor 2–negative (HR+/HER2-) locally advanced metastatic breast cancer (LA/mBC), the INAVO120 trial.

The U.S. Food and Drug Administration (FDA) recently granted Breakthrough Therapy Designation for inavolisib in combination with palbociclib and fulvestrant based on initial results of the study presented at a December 2023 meeting. The phase 3 results showed the inavolisib-based regimen more than doubled progression-free survival (PFS) compared with the two other drugs alone as first-line treatment, researchers reported.

The expanded analysis of the trial, which was presented at the annual meeting of the American Society of Clinical Oncology, looked at additional endpoints, including PFS2 (defined as time from randomization to end of next-line treatment), time to first chemotherapy, key adverse events (AEs) and patient-reported outcomes (PROs).

“Triple combination of inavolisib, a novel PI3K inhibitor, with palbociclib and fulvestrant, resulted in significant and clinically meaningful improvement in PFS (15.0 vs 7.3 months, hazard ratio [HR] 0.43, P less than .0001),” lead investigator Dejan Juric, MD, reported at the meeting, referring to the initial results.

In additional endpoints, the inavolisib-based triplet also “sustained benefit beyond disease progression, delay in chemotherapy initiation, a manageable safety profile, prolonged time to deterioration in pain severity, and maintained quality of life, supporting the overall conclusion that this triple combination is a promising new treatment option for patients with PIK3CA-mutated HR-positive, HER2-negative metastatic breast cancer,” said the oncologist, of Massachusetts General Hospital Cancer Center and assistant professor at Harvard Medical School in Boston.
 

Methods and Results

The trial enrolled 325 patients whose disease had progressed during or within 12 months of adjuvant endocrine therapy (ET) with an aromatase inhibitor or tamoxifen and who had not received prior systemic therapy for recurrent LA/mBC. Patients were enrolled from December 2019 to September 2023 and randomized to either the triplet combination of inavolisib with palbociclib and fulvestrant (n = 161) or the doublet therapy of placebo with palbociclib and fulvestrant (n = 164) until discontinuation due to progressive disease or toxicity.

At the analysis cutoff date at the end of September, 57.8% of patients in the experimental triple therapy arm and 70.1% in the doublet arm had discontinued treatment. In addition, “7.5% versus 11.6% of patients died without subsequent therapy,” said Dr. Juric, and 40.4% of those in the triplet arm, and 50% in the doublet arm received subsequent therapy.

In the expanded analysis, at a median follow-up of 21.3 months, the triplet combination was associated with a PFS2 benefit of 8.9 months over the doublet – meaning patients had 24 months versus 15.1 months from randomization to end of next-line treatment (HR = 0.54). There was a similar benefit in time to first chemotherapy.

Hyperglycemia, diarrhea, rash, and mucosal effects are a known toxicity of PI3K inhibition and were experienced more frequently in the inavolisib arm compared with the placebo arm: (59% vs 9%; 48% vs 16%; 25% vs 17%; and 51% vs 27% respectively). However, “in the vast majority of patients these AEs were experienced in a grade 1 or grade 2 level,” and had resolved by the cutoff date, said Dr. Juric.

There was a 6.2% rate of inavolisib discontinuation due to AEs, but most AEs could be managed with “common approaches” such as metformin for hyperglycemia, loperamide for diarrhea, topical hydrocortisone for rash, and steroid mouthwash for stomatitis/mucosal inflammation, he added.

Patients in the triple treatment arm experienced a longer interval before pain worsened, a median of 30.9 versus 18.1 months, and patient-reported outcomes and health-related quality of life measures showed no decrease with the addition of inavolisib, Dr. Juric reported.
 

Rationale for Using PFS2 as Endpoint

The PFS2 endpoint has emerged with studies of targeted cancer therapies, Kevin Kalinsky, MD, director of the Glenn Family Breast Center at Winship Cancer Institute of Emory University, in Atlanta, said in an interview.

“Presenting PFS2 is not a new thing — we’ve been doing this in other breast cancer studies (of CDK4/6 inhibitors),” said Dr. Kalinsky, a coauthor of the study. “The concern is that you give a drug, and then, after that, things grow so rapidly that then you’re actually not benefiting the patient.

“If you’re giving a targeted agent in the first-line, then the biology changes after that first-line, are you really even making a difference? Or is the drug so toxic that they’re not able to tolerate a next line of treatment?” Dr. Kalinsky continued. “So that’s really the intent of PFS2. The PFS2 included the next line of treatment, so it’s really a first, and second-line representation of treatment. The study presented at ASCO was really about toxicity.”

The study was funded by F. Hoffmann-La Roche Ltd. Dr. Juric disclosed having stock and other ownership interests in PIC Therapeutics, Relay Therapeutics, and Vibliome Therapeutics; consulting or advisory roles with AstraZeneca, Eisai, Genentech, Lilly, MapKure, Novartis, Pfizer, PIC Therapeutics, Relay Therapeutics, and Vibliome Therapeutics; and research funding from Amgen, Arvinas, AstraZeneca, Blueprint Medicines, Eisai, Genentech, Infinity Pharmaceuticals, InventisBio, Novartis, Pfizer, Ribon Therapeutics, Scorpion Therapeutics, Syros Pharmaceuticals, and Takeda.

The experimental drug inavolisib showed sustained benefit combined with standard treatment in advanced, PIK3CA-mutated, hormone receptor–positive, human epidermal growth factor receptor 2–negative (HR+/HER2-) locally advanced metastatic breast cancer (LA/mBC), the INAVO120 trial.

The U.S. Food and Drug Administration (FDA) recently granted Breakthrough Therapy Designation for inavolisib in combination with palbociclib and fulvestrant based on initial results of the study presented at a December 2023 meeting. The phase 3 results showed the inavolisib-based regimen more than doubled progression-free survival (PFS) compared with the two other drugs alone as first-line treatment, researchers reported.

The expanded analysis of the trial, which was presented at the annual meeting of the American Society of Clinical Oncology, looked at additional endpoints, including PFS2 (defined as time from randomization to end of next-line treatment), time to first chemotherapy, key adverse events (AEs) and patient-reported outcomes (PROs).

“Triple combination of inavolisib, a novel PI3K inhibitor, with palbociclib and fulvestrant, resulted in significant and clinically meaningful improvement in PFS (15.0 vs 7.3 months, hazard ratio [HR] 0.43, P less than .0001),” lead investigator Dejan Juric, MD, reported at the meeting, referring to the initial results.

In additional endpoints, the inavolisib-based triplet also “sustained benefit beyond disease progression, delay in chemotherapy initiation, a manageable safety profile, prolonged time to deterioration in pain severity, and maintained quality of life, supporting the overall conclusion that this triple combination is a promising new treatment option for patients with PIK3CA-mutated HR-positive, HER2-negative metastatic breast cancer,” said the oncologist, of Massachusetts General Hospital Cancer Center and assistant professor at Harvard Medical School in Boston.
 

Methods and Results

The trial enrolled 325 patients whose disease had progressed during or within 12 months of adjuvant endocrine therapy (ET) with an aromatase inhibitor or tamoxifen and who had not received prior systemic therapy for recurrent LA/mBC. Patients were enrolled from December 2019 to September 2023 and randomized to either the triplet combination of inavolisib with palbociclib and fulvestrant (n = 161) or the doublet therapy of placebo with palbociclib and fulvestrant (n = 164) until discontinuation due to progressive disease or toxicity.

At the analysis cutoff date at the end of September, 57.8% of patients in the experimental triple therapy arm and 70.1% in the doublet arm had discontinued treatment. In addition, “7.5% versus 11.6% of patients died without subsequent therapy,” said Dr. Juric, and 40.4% of those in the triplet arm, and 50% in the doublet arm received subsequent therapy.

In the expanded analysis, at a median follow-up of 21.3 months, the triplet combination was associated with a PFS2 benefit of 8.9 months over the doublet – meaning patients had 24 months versus 15.1 months from randomization to end of next-line treatment (HR = 0.54). There was a similar benefit in time to first chemotherapy.

Hyperglycemia, diarrhea, rash, and mucosal effects are a known toxicity of PI3K inhibition and were experienced more frequently in the inavolisib arm compared with the placebo arm: (59% vs 9%; 48% vs 16%; 25% vs 17%; and 51% vs 27% respectively). However, “in the vast majority of patients these AEs were experienced in a grade 1 or grade 2 level,” and had resolved by the cutoff date, said Dr. Juric.

There was a 6.2% rate of inavolisib discontinuation due to AEs, but most AEs could be managed with “common approaches” such as metformin for hyperglycemia, loperamide for diarrhea, topical hydrocortisone for rash, and steroid mouthwash for stomatitis/mucosal inflammation, he added.

Patients in the triple treatment arm experienced a longer interval before pain worsened, a median of 30.9 versus 18.1 months, and patient-reported outcomes and health-related quality of life measures showed no decrease with the addition of inavolisib, Dr. Juric reported.
 

Rationale for Using PFS2 as Endpoint

The PFS2 endpoint has emerged with studies of targeted cancer therapies, Kevin Kalinsky, MD, director of the Glenn Family Breast Center at Winship Cancer Institute of Emory University, in Atlanta, said in an interview.

“Presenting PFS2 is not a new thing — we’ve been doing this in other breast cancer studies (of CDK4/6 inhibitors),” said Dr. Kalinsky, a coauthor of the study. “The concern is that you give a drug, and then, after that, things grow so rapidly that then you’re actually not benefiting the patient.

“If you’re giving a targeted agent in the first-line, then the biology changes after that first-line, are you really even making a difference? Or is the drug so toxic that they’re not able to tolerate a next line of treatment?” Dr. Kalinsky continued. “So that’s really the intent of PFS2. The PFS2 included the next line of treatment, so it’s really a first, and second-line representation of treatment. The study presented at ASCO was really about toxicity.”

The study was funded by F. Hoffmann-La Roche Ltd. Dr. Juric disclosed having stock and other ownership interests in PIC Therapeutics, Relay Therapeutics, and Vibliome Therapeutics; consulting or advisory roles with AstraZeneca, Eisai, Genentech, Lilly, MapKure, Novartis, Pfizer, PIC Therapeutics, Relay Therapeutics, and Vibliome Therapeutics; and research funding from Amgen, Arvinas, AstraZeneca, Blueprint Medicines, Eisai, Genentech, Infinity Pharmaceuticals, InventisBio, Novartis, Pfizer, Ribon Therapeutics, Scorpion Therapeutics, Syros Pharmaceuticals, and Takeda.

The experimental drug inavolisib showed sustained benefit combined with standard treatment in advanced, PIK3CA-mutated, hormone receptor–positive, human epidermal growth factor receptor 2–negative (HR+/HER2-) locally advanced metastatic breast cancer (LA/mBC), the INAVO120 trial.

The U.S. Food and Drug Administration (FDA) recently granted Breakthrough Therapy Designation for inavolisib in combination with palbociclib and fulvestrant based on initial results of the study presented at a December 2023 meeting. The phase 3 results showed the inavolisib-based regimen more than doubled progression-free survival (PFS) compared with the two other drugs alone as first-line treatment, researchers reported.

The expanded analysis of the trial, which was presented at the annual meeting of the American Society of Clinical Oncology, looked at additional endpoints, including PFS2 (defined as time from randomization to end of next-line treatment), time to first chemotherapy, key adverse events (AEs) and patient-reported outcomes (PROs).

“Triple combination of inavolisib, a novel PI3K inhibitor, with palbociclib and fulvestrant, resulted in significant and clinically meaningful improvement in PFS (15.0 vs 7.3 months, hazard ratio [HR] 0.43, P less than .0001),” lead investigator Dejan Juric, MD, reported at the meeting, referring to the initial results.

In additional endpoints, the inavolisib-based triplet also “sustained benefit beyond disease progression, delay in chemotherapy initiation, a manageable safety profile, prolonged time to deterioration in pain severity, and maintained quality of life, supporting the overall conclusion that this triple combination is a promising new treatment option for patients with PIK3CA-mutated HR-positive, HER2-negative metastatic breast cancer,” said the oncologist, of Massachusetts General Hospital Cancer Center and assistant professor at Harvard Medical School in Boston.
 

Methods and Results

The trial enrolled 325 patients whose disease had progressed during or within 12 months of adjuvant endocrine therapy (ET) with an aromatase inhibitor or tamoxifen and who had not received prior systemic therapy for recurrent LA/mBC. Patients were enrolled from December 2019 to September 2023 and randomized to either the triplet combination of inavolisib with palbociclib and fulvestrant (n = 161) or the doublet therapy of placebo with palbociclib and fulvestrant (n = 164) until discontinuation due to progressive disease or toxicity.

At the analysis cutoff date at the end of September, 57.8% of patients in the experimental triple therapy arm and 70.1% in the doublet arm had discontinued treatment. In addition, “7.5% versus 11.6% of patients died without subsequent therapy,” said Dr. Juric, and 40.4% of those in the triplet arm, and 50% in the doublet arm received subsequent therapy.

In the expanded analysis, at a median follow-up of 21.3 months, the triplet combination was associated with a PFS2 benefit of 8.9 months over the doublet – meaning patients had 24 months versus 15.1 months from randomization to end of next-line treatment (HR = 0.54). There was a similar benefit in time to first chemotherapy.

Hyperglycemia, diarrhea, rash, and mucosal effects are a known toxicity of PI3K inhibition and were experienced more frequently in the inavolisib arm compared with the placebo arm: (59% vs 9%; 48% vs 16%; 25% vs 17%; and 51% vs 27% respectively). However, “in the vast majority of patients these AEs were experienced in a grade 1 or grade 2 level,” and had resolved by the cutoff date, said Dr. Juric.

There was a 6.2% rate of inavolisib discontinuation due to AEs, but most AEs could be managed with “common approaches” such as metformin for hyperglycemia, loperamide for diarrhea, topical hydrocortisone for rash, and steroid mouthwash for stomatitis/mucosal inflammation, he added.

Patients in the triple treatment arm experienced a longer interval before pain worsened, a median of 30.9 versus 18.1 months, and patient-reported outcomes and health-related quality of life measures showed no decrease with the addition of inavolisib, Dr. Juric reported.
 

Rationale for Using PFS2 as Endpoint

The PFS2 endpoint has emerged with studies of targeted cancer therapies, Kevin Kalinsky, MD, director of the Glenn Family Breast Center at Winship Cancer Institute of Emory University, in Atlanta, said in an interview.

“Presenting PFS2 is not a new thing — we’ve been doing this in other breast cancer studies (of CDK4/6 inhibitors),” said Dr. Kalinsky, a coauthor of the study. “The concern is that you give a drug, and then, after that, things grow so rapidly that then you’re actually not benefiting the patient.

“If you’re giving a targeted agent in the first-line, then the biology changes after that first-line, are you really even making a difference? Or is the drug so toxic that they’re not able to tolerate a next line of treatment?” Dr. Kalinsky continued. “So that’s really the intent of PFS2. The PFS2 included the next line of treatment, so it’s really a first, and second-line representation of treatment. The study presented at ASCO was really about toxicity.”

The study was funded by F. Hoffmann-La Roche Ltd. Dr. Juric disclosed having stock and other ownership interests in PIC Therapeutics, Relay Therapeutics, and Vibliome Therapeutics; consulting or advisory roles with AstraZeneca, Eisai, Genentech, Lilly, MapKure, Novartis, Pfizer, PIC Therapeutics, Relay Therapeutics, and Vibliome Therapeutics; and research funding from Amgen, Arvinas, AstraZeneca, Blueprint Medicines, Eisai, Genentech, Infinity Pharmaceuticals, InventisBio, Novartis, Pfizer, Ribon Therapeutics, Scorpion Therapeutics, Syros Pharmaceuticals, and Takeda.

The Food and Drug Administration has expanded the indication for pembrolizumab (Keytruda, Merck) to include the use of the targeted immunotherapy agent plus chemotherapy followed by single-agent pembrolizumab in adults with primary advanced or recurrent endometrial cancer.

Approval in this setting was granted following priority review and was based on efficacy demonstrated in the randomized, placebo-controlled, phase 3 KEYNOTE-868/NRG-GY018 trial. The multicenter trial showed improved progression-free survival (PFS) with chemotherapy plus pembrolizumab versus chemotherapy plus placebo in patients with stage 3 or 4 disease or stage IVB recurrent disease in two cohorts: 222 patients with mismatch repair (MMR) deficiency, and 588 patients with MMR proficiency.

Among the MMR-deficient patients, median PFS was not reached in the treatment arm and was 6.5 months in the control arm (hazard ratio, 0.30). Among the MMR-proficient patients, the median PFS was 11.1 versus 8.5 months in the study arms, respectively (HR, 0.60), according to an FDA press release.

Patients in both cohorts were randomized 1:1 to receive 200 mg of either pembrolizumab or placebo every 3 weeks, followed by paclitaxel at a dose of 175 mg/m² and carboplatin at a dose of AUC 5 mg/mL/min for six cycles and then 400 mg of pembrolizumab or placebo every 6 weeks for up to 14 cycles.

“Adverse reactions associated with pembrolizumab and chemotherapy were generally similar to those previously reported for pembrolizumab or chemotherapy with the exception of a higher incidence of rash,” the FDA noted.

According to the full prescribing information for pembrolizumab, the recommended dose is 200 mg every 3 weeks or 400 mg every 6 weeks until disease progression, unacceptable toxicity, or for up to 24 months.

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

The Food and Drug Administration has expanded the indication for pembrolizumab (Keytruda, Merck) to include the use of the targeted immunotherapy agent plus chemotherapy followed by single-agent pembrolizumab in adults with primary advanced or recurrent endometrial cancer.

Approval in this setting was granted following priority review and was based on efficacy demonstrated in the randomized, placebo-controlled, phase 3 KEYNOTE-868/NRG-GY018 trial. The multicenter trial showed improved progression-free survival (PFS) with chemotherapy plus pembrolizumab versus chemotherapy plus placebo in patients with stage 3 or 4 disease or stage IVB recurrent disease in two cohorts: 222 patients with mismatch repair (MMR) deficiency, and 588 patients with MMR proficiency.

Among the MMR-deficient patients, median PFS was not reached in the treatment arm and was 6.5 months in the control arm (hazard ratio, 0.30). Among the MMR-proficient patients, the median PFS was 11.1 versus 8.5 months in the study arms, respectively (HR, 0.60), according to an FDA press release.

Patients in both cohorts were randomized 1:1 to receive 200 mg of either pembrolizumab or placebo every 3 weeks, followed by paclitaxel at a dose of 175 mg/m² and carboplatin at a dose of AUC 5 mg/mL/min for six cycles and then 400 mg of pembrolizumab or placebo every 6 weeks for up to 14 cycles.

“Adverse reactions associated with pembrolizumab and chemotherapy were generally similar to those previously reported for pembrolizumab or chemotherapy with the exception of a higher incidence of rash,” the FDA noted.

According to the full prescribing information for pembrolizumab, the recommended dose is 200 mg every 3 weeks or 400 mg every 6 weeks until disease progression, unacceptable toxicity, or for up to 24 months.

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

The Food and Drug Administration has expanded the indication for pembrolizumab (Keytruda, Merck) to include the use of the targeted immunotherapy agent plus chemotherapy followed by single-agent pembrolizumab in adults with primary advanced or recurrent endometrial cancer.

Approval in this setting was granted following priority review and was based on efficacy demonstrated in the randomized, placebo-controlled, phase 3 KEYNOTE-868/NRG-GY018 trial. The multicenter trial showed improved progression-free survival (PFS) with chemotherapy plus pembrolizumab versus chemotherapy plus placebo in patients with stage 3 or 4 disease or stage IVB recurrent disease in two cohorts: 222 patients with mismatch repair (MMR) deficiency, and 588 patients with MMR proficiency.

Among the MMR-deficient patients, median PFS was not reached in the treatment arm and was 6.5 months in the control arm (hazard ratio, 0.30). Among the MMR-proficient patients, the median PFS was 11.1 versus 8.5 months in the study arms, respectively (HR, 0.60), according to an FDA press release.

Patients in both cohorts were randomized 1:1 to receive 200 mg of either pembrolizumab or placebo every 3 weeks, followed by paclitaxel at a dose of 175 mg/m² and carboplatin at a dose of AUC 5 mg/mL/min for six cycles and then 400 mg of pembrolizumab or placebo every 6 weeks for up to 14 cycles.

“Adverse reactions associated with pembrolizumab and chemotherapy were generally similar to those previously reported for pembrolizumab or chemotherapy with the exception of a higher incidence of rash,” the FDA noted.

According to the full prescribing information for pembrolizumab, the recommended dose is 200 mg every 3 weeks or 400 mg every 6 weeks until disease progression, unacceptable toxicity, or for up to 24 months.

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

An ancient Chinese remedy for malaria could offer new hope to the 10% of reproductive-age women living with polycystic ovarian syndrome (PCOS), a poorly understood endocrine disorder that can cause hormonal imbalances, irregular periods, and cysts in the ovaries.

“PCOS is among the most common disorders of reproductive-age women,” said endocrinologist Andrea Dunaif, MD, a professor at the Icahn School of Medicine at Mount Sinai, New York City, who studies diabetes and women’s health. “It is a major risk factor for obesity, type 2 diabetes, and heart disease.” It’s also a leading cause of infertility.

Yet despite how common it is, PCOS has no Food and Drug Administration–approved treatments, though a few early-stage clinical trials are underway. Many women end up taking off-label medications such as oral contraceptives, insulin-sensitizing agents, and antiandrogens to help manage symptoms. Surgery can also be used to treat fertility problems associated with PCOS, though it may not work for everyone.

In a new study, a derivative of artemisinin — a molecule that comes from Artemisia plants, which have been used as far back as 1596 to treat malaria in China — helped relieve PCOS symptoms in rats and a small group of women.

Previously, the study’s lead researcher Qi-qun Tang, MD, PhD, had found that this derivative, called artemether, can increase thermogenesis, boosting metabolism. Dr. Tang and his team at Fudan University, Shanghai, China, wanted to see if it would help with PCOS, which is associated with metabolic problems such as insulin resistance.
 

What the Researchers Did

To simulate PCOS in rats, the team treated the rodents with insulin and human chorionic gonadotropin. Then, they tested artemether on the rats and found that it lowered androgen production in the ovaries.

“A common feature [of PCOS] is that the ovaries, and often the adrenal glands, make increased male hormones, nowhere near what a man makes but slightly above what a normal woman makes,” said Dr. Dunaif, who was not involved in the study.

Artemether “inhibits one of the steroidogenic enzymes, CYP11A1, which is important in the production of male hormones,” Dr. Tang said. It does this by increasing the enzyme’s interaction with a protein called LONP1, triggering the enzyme’s breakdown. Increased levels of LONP1 also appeared to suppress androgen production in the ovaries.

In a pilot clinical study of 19 women with PCOS, taking dihydroartemisinin — an approved drug used to treat malaria that contains active artemisinin derivatives — for 12 weeks substantially reduced serum testosterone and anti-Müllerian hormone levels (which are higher in women with PCOS). Using ultrasound, the researchers found that the antral follicle count (also higher than normal with PCOS) had been reduced. All participants had regular menstrual cycles during treatment. And no one reported significant side effects.

“Regular menstrual cycles suggest that there is ovulation, which can result in conception,” Dr. Dunaif said. Still, testing would be needed to confirm that cycles are ovulatory.

Lowering androgen levels “could improve a substantial portion of the symptoms of PCOS,” said Dr. Dunaif. But the research didn’t see an improvement in insulin sensitivity among the women, suggesting that targeting androgens may not help the metabolic symptoms.
 

What’s Next? 

A larger, placebo-controlled trial would still be needed to assess the drug’s efficacy, said Dr. Dunaif, pointing out that the human study did not have a placebo arm.

And unanswered questions remain. Are there any adrenal effects of the compound? “The enzymes that produce androgens are shared between the ovary and the adrenal [gland],” Dr. Dunaif said, but she pointed out that the study doesn’t address whether there is an adrenal benefit. It’s something to look at in future research.

Still, because artemisinin is an established drug, it may come to market faster than a new molecule would, she said. However, a pharmaceutical company would need to be willing to take on the drug. (Dr. Tang said several companies have already expressed interest.)

And while you can buy artemisinin on the Internet, Dr. Dunaif warned not to start taking it if you have PCOS. “I don’t think we’re at that point,” Dr. Dunaif said.

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

An ancient Chinese remedy for malaria could offer new hope to the 10% of reproductive-age women living with polycystic ovarian syndrome (PCOS), a poorly understood endocrine disorder that can cause hormonal imbalances, irregular periods, and cysts in the ovaries.

“PCOS is among the most common disorders of reproductive-age women,” said endocrinologist Andrea Dunaif, MD, a professor at the Icahn School of Medicine at Mount Sinai, New York City, who studies diabetes and women’s health. “It is a major risk factor for obesity, type 2 diabetes, and heart disease.” It’s also a leading cause of infertility.

Yet despite how common it is, PCOS has no Food and Drug Administration–approved treatments, though a few early-stage clinical trials are underway. Many women end up taking off-label medications such as oral contraceptives, insulin-sensitizing agents, and antiandrogens to help manage symptoms. Surgery can also be used to treat fertility problems associated with PCOS, though it may not work for everyone.

In a new study, a derivative of artemisinin — a molecule that comes from Artemisia plants, which have been used as far back as 1596 to treat malaria in China — helped relieve PCOS symptoms in rats and a small group of women.

Previously, the study’s lead researcher Qi-qun Tang, MD, PhD, had found that this derivative, called artemether, can increase thermogenesis, boosting metabolism. Dr. Tang and his team at Fudan University, Shanghai, China, wanted to see if it would help with PCOS, which is associated with metabolic problems such as insulin resistance.
 

What the Researchers Did

To simulate PCOS in rats, the team treated the rodents with insulin and human chorionic gonadotropin. Then, they tested artemether on the rats and found that it lowered androgen production in the ovaries.

“A common feature [of PCOS] is that the ovaries, and often the adrenal glands, make increased male hormones, nowhere near what a man makes but slightly above what a normal woman makes,” said Dr. Dunaif, who was not involved in the study.

Artemether “inhibits one of the steroidogenic enzymes, CYP11A1, which is important in the production of male hormones,” Dr. Tang said. It does this by increasing the enzyme’s interaction with a protein called LONP1, triggering the enzyme’s breakdown. Increased levels of LONP1 also appeared to suppress androgen production in the ovaries.

In a pilot clinical study of 19 women with PCOS, taking dihydroartemisinin — an approved drug used to treat malaria that contains active artemisinin derivatives — for 12 weeks substantially reduced serum testosterone and anti-Müllerian hormone levels (which are higher in women with PCOS). Using ultrasound, the researchers found that the antral follicle count (also higher than normal with PCOS) had been reduced. All participants had regular menstrual cycles during treatment. And no one reported significant side effects.

“Regular menstrual cycles suggest that there is ovulation, which can result in conception,” Dr. Dunaif said. Still, testing would be needed to confirm that cycles are ovulatory.

Lowering androgen levels “could improve a substantial portion of the symptoms of PCOS,” said Dr. Dunaif. But the research didn’t see an improvement in insulin sensitivity among the women, suggesting that targeting androgens may not help the metabolic symptoms.
 

What’s Next? 

A larger, placebo-controlled trial would still be needed to assess the drug’s efficacy, said Dr. Dunaif, pointing out that the human study did not have a placebo arm.

And unanswered questions remain. Are there any adrenal effects of the compound? “The enzymes that produce androgens are shared between the ovary and the adrenal [gland],” Dr. Dunaif said, but she pointed out that the study doesn’t address whether there is an adrenal benefit. It’s something to look at in future research.

Still, because artemisinin is an established drug, it may come to market faster than a new molecule would, she said. However, a pharmaceutical company would need to be willing to take on the drug. (Dr. Tang said several companies have already expressed interest.)

And while you can buy artemisinin on the Internet, Dr. Dunaif warned not to start taking it if you have PCOS. “I don’t think we’re at that point,” Dr. Dunaif said.

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

An ancient Chinese remedy for malaria could offer new hope to the 10% of reproductive-age women living with polycystic ovarian syndrome (PCOS), a poorly understood endocrine disorder that can cause hormonal imbalances, irregular periods, and cysts in the ovaries.

“PCOS is among the most common disorders of reproductive-age women,” said endocrinologist Andrea Dunaif, MD, a professor at the Icahn School of Medicine at Mount Sinai, New York City, who studies diabetes and women’s health. “It is a major risk factor for obesity, type 2 diabetes, and heart disease.” It’s also a leading cause of infertility.

Yet despite how common it is, PCOS has no Food and Drug Administration–approved treatments, though a few early-stage clinical trials are underway. Many women end up taking off-label medications such as oral contraceptives, insulin-sensitizing agents, and antiandrogens to help manage symptoms. Surgery can also be used to treat fertility problems associated with PCOS, though it may not work for everyone.

In a new study, a derivative of artemisinin — a molecule that comes from Artemisia plants, which have been used as far back as 1596 to treat malaria in China — helped relieve PCOS symptoms in rats and a small group of women.

Previously, the study’s lead researcher Qi-qun Tang, MD, PhD, had found that this derivative, called artemether, can increase thermogenesis, boosting metabolism. Dr. Tang and his team at Fudan University, Shanghai, China, wanted to see if it would help with PCOS, which is associated with metabolic problems such as insulin resistance.
 

What the Researchers Did

To simulate PCOS in rats, the team treated the rodents with insulin and human chorionic gonadotropin. Then, they tested artemether on the rats and found that it lowered androgen production in the ovaries.

“A common feature [of PCOS] is that the ovaries, and often the adrenal glands, make increased male hormones, nowhere near what a man makes but slightly above what a normal woman makes,” said Dr. Dunaif, who was not involved in the study.

Artemether “inhibits one of the steroidogenic enzymes, CYP11A1, which is important in the production of male hormones,” Dr. Tang said. It does this by increasing the enzyme’s interaction with a protein called LONP1, triggering the enzyme’s breakdown. Increased levels of LONP1 also appeared to suppress androgen production in the ovaries.

In a pilot clinical study of 19 women with PCOS, taking dihydroartemisinin — an approved drug used to treat malaria that contains active artemisinin derivatives — for 12 weeks substantially reduced serum testosterone and anti-Müllerian hormone levels (which are higher in women with PCOS). Using ultrasound, the researchers found that the antral follicle count (also higher than normal with PCOS) had been reduced. All participants had regular menstrual cycles during treatment. And no one reported significant side effects.

“Regular menstrual cycles suggest that there is ovulation, which can result in conception,” Dr. Dunaif said. Still, testing would be needed to confirm that cycles are ovulatory.

Lowering androgen levels “could improve a substantial portion of the symptoms of PCOS,” said Dr. Dunaif. But the research didn’t see an improvement in insulin sensitivity among the women, suggesting that targeting androgens may not help the metabolic symptoms.
 

What’s Next? 

A larger, placebo-controlled trial would still be needed to assess the drug’s efficacy, said Dr. Dunaif, pointing out that the human study did not have a placebo arm.

And unanswered questions remain. Are there any adrenal effects of the compound? “The enzymes that produce androgens are shared between the ovary and the adrenal [gland],” Dr. Dunaif said, but she pointed out that the study doesn’t address whether there is an adrenal benefit. It’s something to look at in future research.

Still, because artemisinin is an established drug, it may come to market faster than a new molecule would, she said. However, a pharmaceutical company would need to be willing to take on the drug. (Dr. Tang said several companies have already expressed interest.)

And while you can buy artemisinin on the Internet, Dr. Dunaif warned not to start taking it if you have PCOS. “I don’t think we’re at that point,” Dr. Dunaif said.

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