Van Bavel J, Ravelli AC, Abu-Hanna A, et al. Risk factors for the recurrence of obstetrical anal sphincter injury and the role of a mediolateral episiotomy: an analysis of a national registry. BJOG. 2020;127:951-956.

EXPERT COMMENTARY

Women with a history of OASI are at increased risk for recurrence in a subsequent delivery. Higher rates of anal and fecal incontinence are reported in women with recurrent OASI (rOASI) compared with women who had an OASI only in their first delivery. Previous studies have reported recurrence rates of 5% to 7%,¹ and some suggested that MLE may be protective, but standardized recommendations for mode of delivery and use of MLE currently are not available.

Recently, van Bavel and colleagues sought to determine the rate of rOASI in their population as well as the factors that increase and decrease the risk of this complication.

Details of the study

This cohort study used data from the Dutch Perinatal Registry (Perined) that included 268,607 women who had their first and second deliveries (singleton, term, vertex, < 43 weeks) vaginally in 2000–2009. The study’s primary objective was to determine the rate of rOASI in women who had OASI in their first delivery. The secondary objectives were to identify risk factors for rOASI and to assess the effect of MLE. For the purposes of this study, OASI was defined as subtotal and total rupture of the perineum, or grades 3A-4 as defined by the Royal College of Obstetricians and Gynaecologists.²

Within this cohort, 9,943 women had an OASI in their first delivery (4%), and the rate of rOASI was 5.8% (579 of 9,943). After multivariate analysis, the risk factors for rOASI were birth weight of 4,000 g or greater (odds ratio [OR], 2.1; 95% confidence interval [CI], 1.6–2.6) and duration of the second stage of labor of 30 minutes or longer (OR, 1.8; 95% CI, 1.4–2.3).

The MLE rate was 40.8% (4,054 of 9,943) and was associated with a lower rate of rOASI (OR, 0.3; 95% CI, 0.3–0.4). This association persisted when delivery type was separated into spontaneous and operative vaginal deliveries, with the number of MLEs needed to prevent one rOASI of 22 and 8, respectively. Birth weight of less than 3,000 g also was noted to be protective against rOASI (OR, 0.5; 95% CI, 0.3–0.9).

Based on these findings, as well as comparisons to previous studies, the authors concluded that MLE could be considered for routine use or at least discussed with all women with a prior OASI for prevention of rOASI.

Continue to: Study strengths and limitations...

Study strengths and limitations

A strength of this study was the large number of deliveries and the wide variation of practice included in the registry database, which promotes the generalizability of the results and reduces bias. This also provides an adequate base on which to determine an accurate rate of rOASI in the Dutch population.

One study limitation is that information is not available regarding how the episiotomies were performed (specifically, angle of incision), delivery techniques (“hands on” vs “hands off”), and indication for the episiotomy. Additional limitations suggested are that clinicians who perform an episiotomy may have an inherent bias regarding the protective nature of the procedure and may miss a rOASI due to inadequate examination postprocedure, overestimating its protective effect.

Finally, the relatively high rate of MLE and low rate of cesarean delivery (6.9%) in this study are specific to the Netherlands and do not reflect the obstetric practices used in many other countries. Generalizability of these results in the context of much lower MLE and higher cesarean delivery rates (as in the United States) would therefore be in question.●

Van Bavel J, Ravelli AC, Abu-Hanna A, et al. Risk factors for the recurrence of obstetrical anal sphincter injury and the role of a mediolateral episiotomy: an analysis of a national registry. BJOG. 2020;127:951-956.

EXPERT COMMENTARY

Women with a history of OASI are at increased risk for recurrence in a subsequent delivery. Higher rates of anal and fecal incontinence are reported in women with recurrent OASI (rOASI) compared with women who had an OASI only in their first delivery. Previous studies have reported recurrence rates of 5% to 7%,¹ and some suggested that MLE may be protective, but standardized recommendations for mode of delivery and use of MLE currently are not available.

Recently, van Bavel and colleagues sought to determine the rate of rOASI in their population as well as the factors that increase and decrease the risk of this complication.

Details of the study

This cohort study used data from the Dutch Perinatal Registry (Perined) that included 268,607 women who had their first and second deliveries (singleton, term, vertex, < 43 weeks) vaginally in 2000–2009. The study’s primary objective was to determine the rate of rOASI in women who had OASI in their first delivery. The secondary objectives were to identify risk factors for rOASI and to assess the effect of MLE. For the purposes of this study, OASI was defined as subtotal and total rupture of the perineum, or grades 3A-4 as defined by the Royal College of Obstetricians and Gynaecologists.²

Within this cohort, 9,943 women had an OASI in their first delivery (4%), and the rate of rOASI was 5.8% (579 of 9,943). After multivariate analysis, the risk factors for rOASI were birth weight of 4,000 g or greater (odds ratio [OR], 2.1; 95% confidence interval [CI], 1.6–2.6) and duration of the second stage of labor of 30 minutes or longer (OR, 1.8; 95% CI, 1.4–2.3).

The MLE rate was 40.8% (4,054 of 9,943) and was associated with a lower rate of rOASI (OR, 0.3; 95% CI, 0.3–0.4). This association persisted when delivery type was separated into spontaneous and operative vaginal deliveries, with the number of MLEs needed to prevent one rOASI of 22 and 8, respectively. Birth weight of less than 3,000 g also was noted to be protective against rOASI (OR, 0.5; 95% CI, 0.3–0.9).

Based on these findings, as well as comparisons to previous studies, the authors concluded that MLE could be considered for routine use or at least discussed with all women with a prior OASI for prevention of rOASI.

Continue to: Study strengths and limitations...

Study strengths and limitations

A strength of this study was the large number of deliveries and the wide variation of practice included in the registry database, which promotes the generalizability of the results and reduces bias. This also provides an adequate base on which to determine an accurate rate of rOASI in the Dutch population.

One study limitation is that information is not available regarding how the episiotomies were performed (specifically, angle of incision), delivery techniques (“hands on” vs “hands off”), and indication for the episiotomy. Additional limitations suggested are that clinicians who perform an episiotomy may have an inherent bias regarding the protective nature of the procedure and may miss a rOASI due to inadequate examination postprocedure, overestimating its protective effect.

Finally, the relatively high rate of MLE and low rate of cesarean delivery (6.9%) in this study are specific to the Netherlands and do not reflect the obstetric practices used in many other countries. Generalizability of these results in the context of much lower MLE and higher cesarean delivery rates (as in the United States) would therefore be in question.●

Van Bavel J, Ravelli AC, Abu-Hanna A, et al. Risk factors for the recurrence of obstetrical anal sphincter injury and the role of a mediolateral episiotomy: an analysis of a national registry. BJOG. 2020;127:951-956.

EXPERT COMMENTARY

Women with a history of OASI are at increased risk for recurrence in a subsequent delivery. Higher rates of anal and fecal incontinence are reported in women with recurrent OASI (rOASI) compared with women who had an OASI only in their first delivery. Previous studies have reported recurrence rates of 5% to 7%,¹ and some suggested that MLE may be protective, but standardized recommendations for mode of delivery and use of MLE currently are not available.

Recently, van Bavel and colleagues sought to determine the rate of rOASI in their population as well as the factors that increase and decrease the risk of this complication.

Details of the study

This cohort study used data from the Dutch Perinatal Registry (Perined) that included 268,607 women who had their first and second deliveries (singleton, term, vertex, < 43 weeks) vaginally in 2000–2009. The study’s primary objective was to determine the rate of rOASI in women who had OASI in their first delivery. The secondary objectives were to identify risk factors for rOASI and to assess the effect of MLE. For the purposes of this study, OASI was defined as subtotal and total rupture of the perineum, or grades 3A-4 as defined by the Royal College of Obstetricians and Gynaecologists.²

Within this cohort, 9,943 women had an OASI in their first delivery (4%), and the rate of rOASI was 5.8% (579 of 9,943). After multivariate analysis, the risk factors for rOASI were birth weight of 4,000 g or greater (odds ratio [OR], 2.1; 95% confidence interval [CI], 1.6–2.6) and duration of the second stage of labor of 30 minutes or longer (OR, 1.8; 95% CI, 1.4–2.3).

The MLE rate was 40.8% (4,054 of 9,943) and was associated with a lower rate of rOASI (OR, 0.3; 95% CI, 0.3–0.4). This association persisted when delivery type was separated into spontaneous and operative vaginal deliveries, with the number of MLEs needed to prevent one rOASI of 22 and 8, respectively. Birth weight of less than 3,000 g also was noted to be protective against rOASI (OR, 0.5; 95% CI, 0.3–0.9).

Based on these findings, as well as comparisons to previous studies, the authors concluded that MLE could be considered for routine use or at least discussed with all women with a prior OASI for prevention of rOASI.

Continue to: Study strengths and limitations...

Study strengths and limitations

A strength of this study was the large number of deliveries and the wide variation of practice included in the registry database, which promotes the generalizability of the results and reduces bias. This also provides an adequate base on which to determine an accurate rate of rOASI in the Dutch population.

One study limitation is that information is not available regarding how the episiotomies were performed (specifically, angle of incision), delivery techniques (“hands on” vs “hands off”), and indication for the episiotomy. Additional limitations suggested are that clinicians who perform an episiotomy may have an inherent bias regarding the protective nature of the procedure and may miss a rOASI due to inadequate examination postprocedure, overestimating its protective effect.

Finally, the relatively high rate of MLE and low rate of cesarean delivery (6.9%) in this study are specific to the Netherlands and do not reflect the obstetric practices used in many other countries. Generalizability of these results in the context of much lower MLE and higher cesarean delivery rates (as in the United States) would therefore be in question.●

Simon JA, Al-Hendy A, Archer DF, et al. Elagolix treatment for up to 12 months in women with heavy menstrual bleeding and uterine leiomyomas. Obstet Gynecol. 2020;135:1313-1326.

Expert Commentary

Uterine fibroids are common (occurring in up to 80% of reproductive-age women),^1,2 and often associated with heavy menstrual bleeding (HMB). There are surgical and medical options, but typically medical options are used for short periods of time. Elagolix with hormonal add-back therapy was recently approved (May 29, 2020) by the US Food and Drug Administration (FDA) for treatment of HMB in women with uterine fibroids for up to 24 months.

Elagolix is an oral, nonpeptide gonadotropin-releasing hormone antagonist that results in a dose-dependent reduction of gonadotropins and ovarian sex hormones. There are now 2 approved products containing elagolix, with different indications:

• Orilissa. Elagolix was approved in 2018 by the FDA for moderate to severe pain associated with endometriosis. For that indication there are 2 dose options of elagolix (150 mg for up to 2 years and 200 mg for up to 6 months) and there is no hormonal add-back therapy.
• Oriahnn. Elagolix and hormonal add-back therapy was approved in 2020 for HMB associated with uterine fibroids for up to 24 months. The total daily dose of elagolix is 600 mg (elagolix 300 mg in the morning with estradiol 1 mg/norethindrone acetate 0.5 mg and then in the evening elagolix 300 mg and no hormonal add-back).

This new class of drug, GnRH antagonist, is an important one for women’s health, and emerging science will continue to expand its potential uses, such as in reproductive health, as well as long-term efficacy and safety. The difference in daily dose of elagolix for endometriosis (150 mg for 24 months) compared with HMB associated with fibroids (600 mg for 24 months) is why the hormonal add-back therapy is important and allows for protection of bone density.

This is an important manuscript because it highlights a medical option for women with HMB associated with fibroids, which can be used for a long period of time. Further, the improvement in bleeding is both impressive and maintained in the extension study. Approximately 90% of women show improvement in their menstrual bleeding associated with fibroids.

The question of what to do after 24 months of therapy with elagolix and hormonal add-back therapy is an important one, but providers should recognize that the limiting factor with this elagolix and hormonal add-back therapy is bone mineral density (BMD). We will only learn more and more moving forward if this is a clinically meaningful reason for stopping treatment at 24 months. The FDA takes a strict view of safety, and providers must weigh this with the benefit of therapy.

One other highlight between the 2 approved medications is that Orilissa does not have a black box warning, given that there is no hormonal add-back therapy. Oriahnn does have a warning, regarding thromboembolic disorders and vascular events:

• Estrogen and progestin combinations, including Oriahnn, increase the risk of thrombotic or thromboembolic disorders, especially in women at increased risk for these events.
• Oriahnn is contraindicated in women with current or a history of thrombotic or thromboembolic disorders and in women at increased risk for these events, including women over 35 years of age who smoke or women with uncontrolled hypertension.

Continue to: Details about the study...

Details about the study

The study by Simon et al is an extension study (UF-EXTEND), in that women could participate if they had completed 1 of the 2 pivotal studies on elagolix. The pivotal studies (Elaris UF1 and UF2) were both randomized, double-blinded, placebo-controlled studies with up to 6 months of therapy; for UF-EXTEND, however, participants were randomly assigned to either combined elagolix and hormone replacement therapy or elagolix alone for an additional 6 months of therapy. Although it was known that all participants would receive elagolix in UF-EXTEND, those who received hormonal add-back therapy were blinded. All women were then followed up for an additional 12 months after treatment ended.

The efficacy of elagolix was measured by the objective alkaline hematin method for menstrual blood loss with the a priori coprimary endpoints. The elagolix and hormonal add-back therapy group showed objective improvement in menstrual blood loss at 12 months in 87.9% of women in the extension study (89.4% in the elagolix alone group). This compares with 72.2% improvement at 6 months of treatment in the UF1 and UF2 studies for those taking elagolix and hormonal add-back therapy. These findings illustrate maintenance of the efficacy seen within the 6-month pivotal studies using elagolix over an extended amount of time.

The safety of elagolix also was demonstrated in UF-EXTEND. The 3 most common adverse events were similar to those found in Elaris UF1 and UF2 and included hot flushes, headache, and nausea. In the elagolix and hormonal add-back therapy group during the extension study, the percentage with hot flushes was 7%, headache 6%, and nausea 4%. These are small percentages, which is encouraging for providers and women with HMB associated with fibroids.

Effects on bone density

Bone density was evaluated at baseline in the UF1 and UF2 studies, through treatment, and then 12 months after the extended treatment was stopped. The hormonal add-back therapy of estradiol 1 mg/norethindrone acetate 0.5 mg significantly protected bone density. Some women did not have a decrease in bone density, but for those who did the average was less than 5% for the lumbar spine. The lumbar spine is considered the most reactive, so this illustrates the safety that combined therapy offers women with HMB and fibroids.

The lumbar spine is considered the most reactive, so this site is often used as the main focus with BMD studies. As Simon et al show, the lumbar spine mean BMD percent change from baseline for the elagolix with add-back therapy was -1.5% (95% confidence interval [CI], -1.9 to -1.0) in women who received up to 12 months of treatment at month 6 in the extension study. After stopping elagolix with add-back therapy, at 6 months the elagolix with add-back therapy had a Z-score of -0.6% (95% CI, -1.1 to -0.1). This shows a trend toward baseline, or a recovery within a short time from stopping medication.

Continue to: Study strengths and limitations...

Study strengths and limitations

Strengths of this study include its overall design; efficacy endpoints, which were all established a priori; the fact that measurement of menstrual blood loss was done with the objective alkaline hematin method; and the statistical analysis, which is thorough and well presented. This extension study allowed further evaluation of efficacy and safety for elagolix. Although the authors point out that there may be some selection bias in an extension study, the fact that so many women elected to continue into the extended study is a positive reflection of the treatment.

As providers learn of new therapies for management of HMB associated with fibroids, it is important to consider who will benefit the most. In my opinion, any woman with heavy periods associated with fibroids could be a candidate for elagolix with add-back therapy. This treatment is highly effective, well tolerated, and safe. My approach to management includes educating a woman on all potential therapies and this new option of elagolix and add-back therapy is an important one. The decision for an individual woman on how to manage heavy periods associated with fibroids should consider her contraceptive needs, medical issues, and the risk and benefit of individual therapies. ●

Simon JA, Al-Hendy A, Archer DF, et al. Elagolix treatment for up to 12 months in women with heavy menstrual bleeding and uterine leiomyomas. Obstet Gynecol. 2020;135:1313-1326.

Expert Commentary

Uterine fibroids are common (occurring in up to 80% of reproductive-age women),^1,2 and often associated with heavy menstrual bleeding (HMB). There are surgical and medical options, but typically medical options are used for short periods of time. Elagolix with hormonal add-back therapy was recently approved (May 29, 2020) by the US Food and Drug Administration (FDA) for treatment of HMB in women with uterine fibroids for up to 24 months.

Elagolix is an oral, nonpeptide gonadotropin-releasing hormone antagonist that results in a dose-dependent reduction of gonadotropins and ovarian sex hormones. There are now 2 approved products containing elagolix, with different indications:

• Orilissa. Elagolix was approved in 2018 by the FDA for moderate to severe pain associated with endometriosis. For that indication there are 2 dose options of elagolix (150 mg for up to 2 years and 200 mg for up to 6 months) and there is no hormonal add-back therapy.
• Oriahnn. Elagolix and hormonal add-back therapy was approved in 2020 for HMB associated with uterine fibroids for up to 24 months. The total daily dose of elagolix is 600 mg (elagolix 300 mg in the morning with estradiol 1 mg/norethindrone acetate 0.5 mg and then in the evening elagolix 300 mg and no hormonal add-back).

This new class of drug, GnRH antagonist, is an important one for women’s health, and emerging science will continue to expand its potential uses, such as in reproductive health, as well as long-term efficacy and safety. The difference in daily dose of elagolix for endometriosis (150 mg for 24 months) compared with HMB associated with fibroids (600 mg for 24 months) is why the hormonal add-back therapy is important and allows for protection of bone density.

This is an important manuscript because it highlights a medical option for women with HMB associated with fibroids, which can be used for a long period of time. Further, the improvement in bleeding is both impressive and maintained in the extension study. Approximately 90% of women show improvement in their menstrual bleeding associated with fibroids.

The question of what to do after 24 months of therapy with elagolix and hormonal add-back therapy is an important one, but providers should recognize that the limiting factor with this elagolix and hormonal add-back therapy is bone mineral density (BMD). We will only learn more and more moving forward if this is a clinically meaningful reason for stopping treatment at 24 months. The FDA takes a strict view of safety, and providers must weigh this with the benefit of therapy.

One other highlight between the 2 approved medications is that Orilissa does not have a black box warning, given that there is no hormonal add-back therapy. Oriahnn does have a warning, regarding thromboembolic disorders and vascular events:

• Estrogen and progestin combinations, including Oriahnn, increase the risk of thrombotic or thromboembolic disorders, especially in women at increased risk for these events.
• Oriahnn is contraindicated in women with current or a history of thrombotic or thromboembolic disorders and in women at increased risk for these events, including women over 35 years of age who smoke or women with uncontrolled hypertension.

Continue to: Details about the study...

Details about the study

The study by Simon et al is an extension study (UF-EXTEND), in that women could participate if they had completed 1 of the 2 pivotal studies on elagolix. The pivotal studies (Elaris UF1 and UF2) were both randomized, double-blinded, placebo-controlled studies with up to 6 months of therapy; for UF-EXTEND, however, participants were randomly assigned to either combined elagolix and hormone replacement therapy or elagolix alone for an additional 6 months of therapy. Although it was known that all participants would receive elagolix in UF-EXTEND, those who received hormonal add-back therapy were blinded. All women were then followed up for an additional 12 months after treatment ended.

The efficacy of elagolix was measured by the objective alkaline hematin method for menstrual blood loss with the a priori coprimary endpoints. The elagolix and hormonal add-back therapy group showed objective improvement in menstrual blood loss at 12 months in 87.9% of women in the extension study (89.4% in the elagolix alone group). This compares with 72.2% improvement at 6 months of treatment in the UF1 and UF2 studies for those taking elagolix and hormonal add-back therapy. These findings illustrate maintenance of the efficacy seen within the 6-month pivotal studies using elagolix over an extended amount of time.

The safety of elagolix also was demonstrated in UF-EXTEND. The 3 most common adverse events were similar to those found in Elaris UF1 and UF2 and included hot flushes, headache, and nausea. In the elagolix and hormonal add-back therapy group during the extension study, the percentage with hot flushes was 7%, headache 6%, and nausea 4%. These are small percentages, which is encouraging for providers and women with HMB associated with fibroids.

Effects on bone density

Bone density was evaluated at baseline in the UF1 and UF2 studies, through treatment, and then 12 months after the extended treatment was stopped. The hormonal add-back therapy of estradiol 1 mg/norethindrone acetate 0.5 mg significantly protected bone density. Some women did not have a decrease in bone density, but for those who did the average was less than 5% for the lumbar spine. The lumbar spine is considered the most reactive, so this illustrates the safety that combined therapy offers women with HMB and fibroids.

The lumbar spine is considered the most reactive, so this site is often used as the main focus with BMD studies. As Simon et al show, the lumbar spine mean BMD percent change from baseline for the elagolix with add-back therapy was -1.5% (95% confidence interval [CI], -1.9 to -1.0) in women who received up to 12 months of treatment at month 6 in the extension study. After stopping elagolix with add-back therapy, at 6 months the elagolix with add-back therapy had a Z-score of -0.6% (95% CI, -1.1 to -0.1). This shows a trend toward baseline, or a recovery within a short time from stopping medication.

Continue to: Study strengths and limitations...

Study strengths and limitations

Strengths of this study include its overall design; efficacy endpoints, which were all established a priori; the fact that measurement of menstrual blood loss was done with the objective alkaline hematin method; and the statistical analysis, which is thorough and well presented. This extension study allowed further evaluation of efficacy and safety for elagolix. Although the authors point out that there may be some selection bias in an extension study, the fact that so many women elected to continue into the extended study is a positive reflection of the treatment.

As providers learn of new therapies for management of HMB associated with fibroids, it is important to consider who will benefit the most. In my opinion, any woman with heavy periods associated with fibroids could be a candidate for elagolix with add-back therapy. This treatment is highly effective, well tolerated, and safe. My approach to management includes educating a woman on all potential therapies and this new option of elagolix and add-back therapy is an important one. The decision for an individual woman on how to manage heavy periods associated with fibroids should consider her contraceptive needs, medical issues, and the risk and benefit of individual therapies. ●

Simon JA, Al-Hendy A, Archer DF, et al. Elagolix treatment for up to 12 months in women with heavy menstrual bleeding and uterine leiomyomas. Obstet Gynecol. 2020;135:1313-1326.

Expert Commentary

Uterine fibroids are common (occurring in up to 80% of reproductive-age women),^1,2 and often associated with heavy menstrual bleeding (HMB). There are surgical and medical options, but typically medical options are used for short periods of time. Elagolix with hormonal add-back therapy was recently approved (May 29, 2020) by the US Food and Drug Administration (FDA) for treatment of HMB in women with uterine fibroids for up to 24 months.

Elagolix is an oral, nonpeptide gonadotropin-releasing hormone antagonist that results in a dose-dependent reduction of gonadotropins and ovarian sex hormones. There are now 2 approved products containing elagolix, with different indications:

• Orilissa. Elagolix was approved in 2018 by the FDA for moderate to severe pain associated with endometriosis. For that indication there are 2 dose options of elagolix (150 mg for up to 2 years and 200 mg for up to 6 months) and there is no hormonal add-back therapy.
• Oriahnn. Elagolix and hormonal add-back therapy was approved in 2020 for HMB associated with uterine fibroids for up to 24 months. The total daily dose of elagolix is 600 mg (elagolix 300 mg in the morning with estradiol 1 mg/norethindrone acetate 0.5 mg and then in the evening elagolix 300 mg and no hormonal add-back).

This new class of drug, GnRH antagonist, is an important one for women’s health, and emerging science will continue to expand its potential uses, such as in reproductive health, as well as long-term efficacy and safety. The difference in daily dose of elagolix for endometriosis (150 mg for 24 months) compared with HMB associated with fibroids (600 mg for 24 months) is why the hormonal add-back therapy is important and allows for protection of bone density.

This is an important manuscript because it highlights a medical option for women with HMB associated with fibroids, which can be used for a long period of time. Further, the improvement in bleeding is both impressive and maintained in the extension study. Approximately 90% of women show improvement in their menstrual bleeding associated with fibroids.

The question of what to do after 24 months of therapy with elagolix and hormonal add-back therapy is an important one, but providers should recognize that the limiting factor with this elagolix and hormonal add-back therapy is bone mineral density (BMD). We will only learn more and more moving forward if this is a clinically meaningful reason for stopping treatment at 24 months. The FDA takes a strict view of safety, and providers must weigh this with the benefit of therapy.

One other highlight between the 2 approved medications is that Orilissa does not have a black box warning, given that there is no hormonal add-back therapy. Oriahnn does have a warning, regarding thromboembolic disorders and vascular events:

• Estrogen and progestin combinations, including Oriahnn, increase the risk of thrombotic or thromboembolic disorders, especially in women at increased risk for these events.
• Oriahnn is contraindicated in women with current or a history of thrombotic or thromboembolic disorders and in women at increased risk for these events, including women over 35 years of age who smoke or women with uncontrolled hypertension.

Continue to: Details about the study...

Details about the study

The study by Simon et al is an extension study (UF-EXTEND), in that women could participate if they had completed 1 of the 2 pivotal studies on elagolix. The pivotal studies (Elaris UF1 and UF2) were both randomized, double-blinded, placebo-controlled studies with up to 6 months of therapy; for UF-EXTEND, however, participants were randomly assigned to either combined elagolix and hormone replacement therapy or elagolix alone for an additional 6 months of therapy. Although it was known that all participants would receive elagolix in UF-EXTEND, those who received hormonal add-back therapy were blinded. All women were then followed up for an additional 12 months after treatment ended.

The efficacy of elagolix was measured by the objective alkaline hematin method for menstrual blood loss with the a priori coprimary endpoints. The elagolix and hormonal add-back therapy group showed objective improvement in menstrual blood loss at 12 months in 87.9% of women in the extension study (89.4% in the elagolix alone group). This compares with 72.2% improvement at 6 months of treatment in the UF1 and UF2 studies for those taking elagolix and hormonal add-back therapy. These findings illustrate maintenance of the efficacy seen within the 6-month pivotal studies using elagolix over an extended amount of time.

The safety of elagolix also was demonstrated in UF-EXTEND. The 3 most common adverse events were similar to those found in Elaris UF1 and UF2 and included hot flushes, headache, and nausea. In the elagolix and hormonal add-back therapy group during the extension study, the percentage with hot flushes was 7%, headache 6%, and nausea 4%. These are small percentages, which is encouraging for providers and women with HMB associated with fibroids.

Effects on bone density

Bone density was evaluated at baseline in the UF1 and UF2 studies, through treatment, and then 12 months after the extended treatment was stopped. The hormonal add-back therapy of estradiol 1 mg/norethindrone acetate 0.5 mg significantly protected bone density. Some women did not have a decrease in bone density, but for those who did the average was less than 5% for the lumbar spine. The lumbar spine is considered the most reactive, so this illustrates the safety that combined therapy offers women with HMB and fibroids.

The lumbar spine is considered the most reactive, so this site is often used as the main focus with BMD studies. As Simon et al show, the lumbar spine mean BMD percent change from baseline for the elagolix with add-back therapy was -1.5% (95% confidence interval [CI], -1.9 to -1.0) in women who received up to 12 months of treatment at month 6 in the extension study. After stopping elagolix with add-back therapy, at 6 months the elagolix with add-back therapy had a Z-score of -0.6% (95% CI, -1.1 to -0.1). This shows a trend toward baseline, or a recovery within a short time from stopping medication.

Continue to: Study strengths and limitations...

Study strengths and limitations

Strengths of this study include its overall design; efficacy endpoints, which were all established a priori; the fact that measurement of menstrual blood loss was done with the objective alkaline hematin method; and the statistical analysis, which is thorough and well presented. This extension study allowed further evaluation of efficacy and safety for elagolix. Although the authors point out that there may be some selection bias in an extension study, the fact that so many women elected to continue into the extended study is a positive reflection of the treatment.

As providers learn of new therapies for management of HMB associated with fibroids, it is important to consider who will benefit the most. In my opinion, any woman with heavy periods associated with fibroids could be a candidate for elagolix with add-back therapy. This treatment is highly effective, well tolerated, and safe. My approach to management includes educating a woman on all potential therapies and this new option of elagolix and add-back therapy is an important one. The decision for an individual woman on how to manage heavy periods associated with fibroids should consider her contraceptive needs, medical issues, and the risk and benefit of individual therapies. ●

Danicamtiv, a novel oral selective cardiac myosin activator, demonstrated promising beneficial effects on left ventricular systolic function coupled with marked improvements in left atrial volume and function in patients with heart failure with reduced ejection fraction in a phase 2a clinical trial, Adriaan A. Voors, MD, PhD, said at the European Society of Cardiology Heart Failure Discoveries virtual meeting.

Importantly, these improvements weren’t accompanied by any unwelcome significant increase in diastolic stiffness, added Dr. Voors, a cardiologist at the University of Groningen (the Netherlands).

This is a drug whose novel mechanism of action could make it a good fit in combination with existing guideline-recommended therapies known to improve morbidity and mortality in patients with heart failure with reduced ejection fraction (HFrEF), none of which do what danicamtiv does: namely, activates cardiac myosin by enhancing myofibrillar adenosine triphosphatase activity, thereby boosting intrinsic myocardial contractility without any impact upon calcium homeostasis, he explained.

Dr. Voors reported on 40 patients with stable HFrEF and a left ventricular ejection fraction of 35% or less, all on background guideline-directed medical therapy. They were randomized double blind to 7 days of danicamtiv at 50, 75, or 100 mg twice daily, or placebo. A total of 489 ECGs were performed in conjunction with blood draws to measure plasma drug concentrations during the study.

Danicamtiv significantly improved left ventricular stroke volume and global longitudinal and circumferential strain in plasma drug concentration–dependent fashion, while simultaneously decreasing left ventricular end-systolic and end-diastolic diameters. Danicamtiv increased systolic ejection time from 286 milliseconds at baseline by an additional placebo-corrected 15, 36, and 48 milliseconds in patients with low, mid-range, and high drug concentrations.

The cardiac myosin activator’s concentration-dependent salutary effects on left atrial (LA) parameters in this brief study were intriguing, since LA function is often compromised in patients with heart failure and has been shown in prior observational studies to independently predict cardiovascular outcomes, the cardiologist noted. The favorable changes in response to danicamtiv included a reduction in LA minimal volume index and an increase in LA emptying fraction. Also, there were marked improvements in LA function index, by 6.1 and 5.8 points, respectively, in patients with mid- and high drug concentrations, from a baseline of 26 points.

Holter monitoring revealed no increased risk of atrial or ventricular arrhythmias in study participants.

Treatment-emergent adverse events were mild and/or unrelated to treatment and showed no particular pattern. The one serious adverse event in the study was a case of hyperkalemia deemed by investigators to be unrelated to treatment.

Seven of 30 danicamtiv-treated patients developed mild, transient, asymptomatic increases in serum cardiac troponin I and/or high-sensitivity troponin T. Dr. Voors said the significance of this must await further examination in larger clinical trials. A phase 2 clinical trial in patients with HFrEF and paroxysmal or persistent atrial fibrillation is planned in order to learn if chronic therapy with danicamtiv results in sustained LA remodeling and clinical benefits. Another planned phase 2 study will be conducted in patients with selected forms of genetic dilated cardiomyopathy.

Because danicamtiv appears to have no effects on blood pressure, renal function, or electrolytes, Dr. Voors speculated that the drug might prove to be an attractive therapeutic option in patients with advanced refractory heart failure, who often have low blood pressure, poor renal function, and a very low left ventricular ejection fraction.

Discussant Thomas Thum, MD, PhD, commented that danicamtiv has definitely earned an opportunity to show what it can do in larger, long-term clinical trials. He was impressed by the significant increase in systolic ejection time, a good marker for cardiac contractility. But he added that the troponin signal warrants careful scrutiny.

“The slight increase over baseline in the phase 2a study was not correlated with any ECG changes or clinical symptoms. However, whether this is a detrimental biomarker sign of a silent harm to the heart remains to be investigated,” said Dr. Thum, a cardiologist at the Institute of Molecular and Translational Therapeutic Strategies at Hannover (Germany) Medical School.

The phase 2a study finding of a plasma drug concentration–dependent prolongation in isovolumetric relaxation time “warrants some caution in future clinical development in patients with impaired diastolic function,” he added.

Simultaneous with Dr. Voors’ presentation, the study results were published online (Eur J Heart Fail. 2020 Jun 19. doi: 10.1002/ejhf.1933).

The danicamtiv study was sponsored by MyoKardia. Dr. Voors reported receiving research funding from and serving as a consultant to MyoKardia and numerous other companies.

[email protected]

Danicamtiv, a novel oral selective cardiac myosin activator, demonstrated promising beneficial effects on left ventricular systolic function coupled with marked improvements in left atrial volume and function in patients with heart failure with reduced ejection fraction in a phase 2a clinical trial, Adriaan A. Voors, MD, PhD, said at the European Society of Cardiology Heart Failure Discoveries virtual meeting.

Importantly, these improvements weren’t accompanied by any unwelcome significant increase in diastolic stiffness, added Dr. Voors, a cardiologist at the University of Groningen (the Netherlands).

This is a drug whose novel mechanism of action could make it a good fit in combination with existing guideline-recommended therapies known to improve morbidity and mortality in patients with heart failure with reduced ejection fraction (HFrEF), none of which do what danicamtiv does: namely, activates cardiac myosin by enhancing myofibrillar adenosine triphosphatase activity, thereby boosting intrinsic myocardial contractility without any impact upon calcium homeostasis, he explained.

Dr. Voors reported on 40 patients with stable HFrEF and a left ventricular ejection fraction of 35% or less, all on background guideline-directed medical therapy. They were randomized double blind to 7 days of danicamtiv at 50, 75, or 100 mg twice daily, or placebo. A total of 489 ECGs were performed in conjunction with blood draws to measure plasma drug concentrations during the study.

Danicamtiv significantly improved left ventricular stroke volume and global longitudinal and circumferential strain in plasma drug concentration–dependent fashion, while simultaneously decreasing left ventricular end-systolic and end-diastolic diameters. Danicamtiv increased systolic ejection time from 286 milliseconds at baseline by an additional placebo-corrected 15, 36, and 48 milliseconds in patients with low, mid-range, and high drug concentrations.

The cardiac myosin activator’s concentration-dependent salutary effects on left atrial (LA) parameters in this brief study were intriguing, since LA function is often compromised in patients with heart failure and has been shown in prior observational studies to independently predict cardiovascular outcomes, the cardiologist noted. The favorable changes in response to danicamtiv included a reduction in LA minimal volume index and an increase in LA emptying fraction. Also, there were marked improvements in LA function index, by 6.1 and 5.8 points, respectively, in patients with mid- and high drug concentrations, from a baseline of 26 points.

Holter monitoring revealed no increased risk of atrial or ventricular arrhythmias in study participants.

Treatment-emergent adverse events were mild and/or unrelated to treatment and showed no particular pattern. The one serious adverse event in the study was a case of hyperkalemia deemed by investigators to be unrelated to treatment.

Seven of 30 danicamtiv-treated patients developed mild, transient, asymptomatic increases in serum cardiac troponin I and/or high-sensitivity troponin T. Dr. Voors said the significance of this must await further examination in larger clinical trials. A phase 2 clinical trial in patients with HFrEF and paroxysmal or persistent atrial fibrillation is planned in order to learn if chronic therapy with danicamtiv results in sustained LA remodeling and clinical benefits. Another planned phase 2 study will be conducted in patients with selected forms of genetic dilated cardiomyopathy.

Because danicamtiv appears to have no effects on blood pressure, renal function, or electrolytes, Dr. Voors speculated that the drug might prove to be an attractive therapeutic option in patients with advanced refractory heart failure, who often have low blood pressure, poor renal function, and a very low left ventricular ejection fraction.

Discussant Thomas Thum, MD, PhD, commented that danicamtiv has definitely earned an opportunity to show what it can do in larger, long-term clinical trials. He was impressed by the significant increase in systolic ejection time, a good marker for cardiac contractility. But he added that the troponin signal warrants careful scrutiny.

“The slight increase over baseline in the phase 2a study was not correlated with any ECG changes or clinical symptoms. However, whether this is a detrimental biomarker sign of a silent harm to the heart remains to be investigated,” said Dr. Thum, a cardiologist at the Institute of Molecular and Translational Therapeutic Strategies at Hannover (Germany) Medical School.

The phase 2a study finding of a plasma drug concentration–dependent prolongation in isovolumetric relaxation time “warrants some caution in future clinical development in patients with impaired diastolic function,” he added.

Simultaneous with Dr. Voors’ presentation, the study results were published online (Eur J Heart Fail. 2020 Jun 19. doi: 10.1002/ejhf.1933).

The danicamtiv study was sponsored by MyoKardia. Dr. Voors reported receiving research funding from and serving as a consultant to MyoKardia and numerous other companies.

[email protected]

Danicamtiv, a novel oral selective cardiac myosin activator, demonstrated promising beneficial effects on left ventricular systolic function coupled with marked improvements in left atrial volume and function in patients with heart failure with reduced ejection fraction in a phase 2a clinical trial, Adriaan A. Voors, MD, PhD, said at the European Society of Cardiology Heart Failure Discoveries virtual meeting.

Importantly, these improvements weren’t accompanied by any unwelcome significant increase in diastolic stiffness, added Dr. Voors, a cardiologist at the University of Groningen (the Netherlands).

This is a drug whose novel mechanism of action could make it a good fit in combination with existing guideline-recommended therapies known to improve morbidity and mortality in patients with heart failure with reduced ejection fraction (HFrEF), none of which do what danicamtiv does: namely, activates cardiac myosin by enhancing myofibrillar adenosine triphosphatase activity, thereby boosting intrinsic myocardial contractility without any impact upon calcium homeostasis, he explained.

Dr. Voors reported on 40 patients with stable HFrEF and a left ventricular ejection fraction of 35% or less, all on background guideline-directed medical therapy. They were randomized double blind to 7 days of danicamtiv at 50, 75, or 100 mg twice daily, or placebo. A total of 489 ECGs were performed in conjunction with blood draws to measure plasma drug concentrations during the study.

Danicamtiv significantly improved left ventricular stroke volume and global longitudinal and circumferential strain in plasma drug concentration–dependent fashion, while simultaneously decreasing left ventricular end-systolic and end-diastolic diameters. Danicamtiv increased systolic ejection time from 286 milliseconds at baseline by an additional placebo-corrected 15, 36, and 48 milliseconds in patients with low, mid-range, and high drug concentrations.

The cardiac myosin activator’s concentration-dependent salutary effects on left atrial (LA) parameters in this brief study were intriguing, since LA function is often compromised in patients with heart failure and has been shown in prior observational studies to independently predict cardiovascular outcomes, the cardiologist noted. The favorable changes in response to danicamtiv included a reduction in LA minimal volume index and an increase in LA emptying fraction. Also, there were marked improvements in LA function index, by 6.1 and 5.8 points, respectively, in patients with mid- and high drug concentrations, from a baseline of 26 points.

Holter monitoring revealed no increased risk of atrial or ventricular arrhythmias in study participants.

Treatment-emergent adverse events were mild and/or unrelated to treatment and showed no particular pattern. The one serious adverse event in the study was a case of hyperkalemia deemed by investigators to be unrelated to treatment.

Seven of 30 danicamtiv-treated patients developed mild, transient, asymptomatic increases in serum cardiac troponin I and/or high-sensitivity troponin T. Dr. Voors said the significance of this must await further examination in larger clinical trials. A phase 2 clinical trial in patients with HFrEF and paroxysmal or persistent atrial fibrillation is planned in order to learn if chronic therapy with danicamtiv results in sustained LA remodeling and clinical benefits. Another planned phase 2 study will be conducted in patients with selected forms of genetic dilated cardiomyopathy.

Because danicamtiv appears to have no effects on blood pressure, renal function, or electrolytes, Dr. Voors speculated that the drug might prove to be an attractive therapeutic option in patients with advanced refractory heart failure, who often have low blood pressure, poor renal function, and a very low left ventricular ejection fraction.

Discussant Thomas Thum, MD, PhD, commented that danicamtiv has definitely earned an opportunity to show what it can do in larger, long-term clinical trials. He was impressed by the significant increase in systolic ejection time, a good marker for cardiac contractility. But he added that the troponin signal warrants careful scrutiny.

“The slight increase over baseline in the phase 2a study was not correlated with any ECG changes or clinical symptoms. However, whether this is a detrimental biomarker sign of a silent harm to the heart remains to be investigated,” said Dr. Thum, a cardiologist at the Institute of Molecular and Translational Therapeutic Strategies at Hannover (Germany) Medical School.

The phase 2a study finding of a plasma drug concentration–dependent prolongation in isovolumetric relaxation time “warrants some caution in future clinical development in patients with impaired diastolic function,” he added.

Simultaneous with Dr. Voors’ presentation, the study results were published online (Eur J Heart Fail. 2020 Jun 19. doi: 10.1002/ejhf.1933).

The danicamtiv study was sponsored by MyoKardia. Dr. Voors reported receiving research funding from and serving as a consultant to MyoKardia and numerous other companies.

[email protected]

Obstetricians know that a cesarean delivery (CD) for a woman with a prolonged second stage and a fetal head deeply impacted in the pelvis is challenging. In this situation, extensions of the uterine incision commonly occur, resulting in prolonged operative time and increased blood loss. Even more harrowing is the inability to deliver the fetal head, necessitating emergency assistance from other clinicians. In this situation, interventions that may be helpful include:

• extend or T the uterine incision
• enlist the aid of a clinician to push up on the fetal head with a vaginal hand (FIGURE 1)
• reverse breech extraction (FIGURE 2), and
• vaginal insertion of a Fetal Pillow prior to starting the delivery.

Evidence from clinical trials indicates that reverse breech extraction or insertion of a Fetal Pillow result in the best clinical outcomes.

Reverse breech extraction vs the push technique

Although the data are limited, most studies report that compared with pushing up with a vaginal hand (as shown in Figure 1), the reverse breech extraction technique (as shown in Figure 2) is associated with a reduction in extensions of the uterine incision, reduced blood loss, and reduced operative time.¹ In a randomized trial, 108 women with obstructed labor undergoing CD in the second stage were randomly assigned to reverse breech extraction or pushing up with a vaginal hand.² Following the uterine incision, the reverse breech extraction technique is performed by immediately reaching into the upper uterus and grasping the lower portion of the fetal leg and applying gentle traction on the leg until the second leg appeared. The lower legs are then pulled out of the uterus. Standard breech delivery maneuvers are used to deliver the shoulders and head. In the trial, compared with the push technique, reverse breech extraction was associated with fewer extensions of the uterine incision (30% vs 11%; P<.05), less blood loss (899 mL vs 1,257 mL; P<.001), and shorter operative time (56 min vs 89 min, P<.001). Fetal injury was similar with the push and breech extraction techniques (6% and 7%).

In another randomized trial, 192 women undergoing CD for obstructed labor were randomly assigned to reverse breech extraction or pushing the head up with a hand in the vagina.³ Compared with the vaginal push technique, reverse breech extraction was associated with fewer extensions of the uterine incision (19% vs 48%; P = .003), fewer cases of wound infection (2% vs 13%; P = .007), and fewer blood transfusions (2 vs 11; P = .012).

Additional options and adjuvants for facilitating delivery of a fetal head deeply impacted in the pelvis include: using a Coyne spoon, using nitroglycerine or terbutaline to relax the myometrium, breaking the vaginal suction on the fetal head before attempting delivery, keeping the wrist of the delivering hand as straight as possible to reduce uterine incision extensions, and incising the ring (if a Bandl’s ring is detected).

Continue to: The Fetal Pillow...

The Fetal Pillow

The Fetal Pillow (Safe Obstetric Systems, New York, New York) is a single-use fetal cephalic elevation device for managing the deeply impacted fetal head (FIGURE 3). The Fetal Pillow has a firm plastic base upon which is attached a soft silicon balloon. The Fetal Pillow is inserted into the vagina prior to initiating CD and the balloon is filled with 180 mL of saline, causing the fetal head to be pushed to a higher station (FIGURE 4). Use of the Fetal Pillow may be indicated prior to CD in the following situations:

• second stage labor with a deeply impacted head
• second stage labor and failed operative delivery
• occiput posterior position or deep transverse arrest
• absent progress in the first stage between 8 cm and 10 cm with a deeply impacted fetal head or excessive caput of the fetal head.

The Fetal Pillow is inserted after completing vaginal preparation for CD and before initiating skin preparation and abdominal draping. The steps for inserting the Fetal Pillow include:

1. Use the 60 mL syringe to fully deflate the Fetal Pillow and leave the cock-stop open.
2. Fold the Fetal Pillow by squeezing the firm plastic base, and with the patient’s legs in a frog-leg position, place the device in the vagina.
3. Allow the firm plastic base to open to a flat position with the base against the posterior vaginal wall and the soft silicon balloon against the fetal head.
4. Using pressure on the plastic base, gently push the Fetal Pillow posteriorly toward the sacrum of the mother.
5. Use the 60 mL syringe to inflate the balloon with 180 mL of normal saline and close the valve.
6. Straighten the patient’s legs and proceed with skin preparation and abdominal draping (FIGURE 4).

When the CD is completed, deflate the balloon by drawing out the saline with the 60 mL syringe and remove the device by hooking a finger around the firm plastic base. The Fetal Pillow is surprisingly easy to use.

Continue to: Effectiveness of the Fetal Pillow...

Effectiveness of the Fetal Pillow

In one randomized trial, 240 women undergoing CD were randomly allocated to a group in which the Fetal Pillow was placed in the vagina and inflated prior to the cesarean and a control group in which the Fetal Pillow was not used. In this study the mean length of the second stage averaged 1.9 hours.⁴ Compared with no Fetal Pillow, use of the Fetal Pillow was associated with a reduction in grade 3 extension of the uterine incision (extension into the uterine artery, vagina, or bladder) (2.5% vs 23%), a reduction in blood loss > 1,000 mL (4% vs 22%), and fewer difficult plus very difficult deliveries of the fetal head as reported by the surgeon (6% vs 39%).

In another randomized trial, 60 nulliparous women undergoing CD in the second stage of labor had a Fetal Pillow inserted in the vagina and were randomly allocated to inflation of the pillow (Fetal Pillow group) or noninflation of the pillow (control group).⁵ In this study the mean length of the second stage was 4 hours. Compared with noninflation of the Fetal Pillow, use of the inflated Fetal Pillow was associated with a reduction in grade 3 extension of the uterine incision (extensions into the uterine artery, vagina, or bladder) (0% for inflation vs 13% for noninflation) and fewer difficult plus very difficult deliveries of the fetal head as reported by the surgeon (0% for inflation vs 37% for noninflation). There was no significant difference in blood loss between the two groups (800 mL vs 900 mL). These two randomized studies both reported that the use of the Fetal Pillow was associated with a reduction in grade 3 extensions of the uterine incision and a decrease in the difficulty of delivering the fetal head.

Consider trialing the Fetal Pillow

When a CD is performed after a prolonged second stage of labor, surgical complications are common, including extensions of the uterine incision and difficulty delivering the fetal head. When a grade 3 extension occurs—with tearing of a uterine artery, deep extension into the vagina, or damage to the bladder—the surgical repair can be extraordinarily challenging. Clinical trials report that both reverse breech extraction and the Fetal Pillow can facilitate CD in the setting of a prolonged second stage. For many obstetricians reverse breech extraction is a challenging obstetric maneuver. The insertion and inflation of a Fetal Pillow is a simple procedure. Obstetrician-gynecologists learn by doing. If you have never used the Fetal Pillow, I suggest you consider trialing it in your practice. ●

Obstetricians know that a cesarean delivery (CD) for a woman with a prolonged second stage and a fetal head deeply impacted in the pelvis is challenging. In this situation, extensions of the uterine incision commonly occur, resulting in prolonged operative time and increased blood loss. Even more harrowing is the inability to deliver the fetal head, necessitating emergency assistance from other clinicians. In this situation, interventions that may be helpful include:

• extend or T the uterine incision
• enlist the aid of a clinician to push up on the fetal head with a vaginal hand (FIGURE 1)
• reverse breech extraction (FIGURE 2), and
• vaginal insertion of a Fetal Pillow prior to starting the delivery.

Evidence from clinical trials indicates that reverse breech extraction or insertion of a Fetal Pillow result in the best clinical outcomes.

Reverse breech extraction vs the push technique

Although the data are limited, most studies report that compared with pushing up with a vaginal hand (as shown in Figure 1), the reverse breech extraction technique (as shown in Figure 2) is associated with a reduction in extensions of the uterine incision, reduced blood loss, and reduced operative time.¹ In a randomized trial, 108 women with obstructed labor undergoing CD in the second stage were randomly assigned to reverse breech extraction or pushing up with a vaginal hand.² Following the uterine incision, the reverse breech extraction technique is performed by immediately reaching into the upper uterus and grasping the lower portion of the fetal leg and applying gentle traction on the leg until the second leg appeared. The lower legs are then pulled out of the uterus. Standard breech delivery maneuvers are used to deliver the shoulders and head. In the trial, compared with the push technique, reverse breech extraction was associated with fewer extensions of the uterine incision (30% vs 11%; P<.05), less blood loss (899 mL vs 1,257 mL; P<.001), and shorter operative time (56 min vs 89 min, P<.001). Fetal injury was similar with the push and breech extraction techniques (6% and 7%).

In another randomized trial, 192 women undergoing CD for obstructed labor were randomly assigned to reverse breech extraction or pushing the head up with a hand in the vagina.³ Compared with the vaginal push technique, reverse breech extraction was associated with fewer extensions of the uterine incision (19% vs 48%; P = .003), fewer cases of wound infection (2% vs 13%; P = .007), and fewer blood transfusions (2 vs 11; P = .012).

Additional options and adjuvants for facilitating delivery of a fetal head deeply impacted in the pelvis include: using a Coyne spoon, using nitroglycerine or terbutaline to relax the myometrium, breaking the vaginal suction on the fetal head before attempting delivery, keeping the wrist of the delivering hand as straight as possible to reduce uterine incision extensions, and incising the ring (if a Bandl’s ring is detected).

Continue to: The Fetal Pillow...

The Fetal Pillow

The Fetal Pillow (Safe Obstetric Systems, New York, New York) is a single-use fetal cephalic elevation device for managing the deeply impacted fetal head (FIGURE 3). The Fetal Pillow has a firm plastic base upon which is attached a soft silicon balloon. The Fetal Pillow is inserted into the vagina prior to initiating CD and the balloon is filled with 180 mL of saline, causing the fetal head to be pushed to a higher station (FIGURE 4). Use of the Fetal Pillow may be indicated prior to CD in the following situations:

• second stage labor with a deeply impacted head
• second stage labor and failed operative delivery
• occiput posterior position or deep transverse arrest
• absent progress in the first stage between 8 cm and 10 cm with a deeply impacted fetal head or excessive caput of the fetal head.

The Fetal Pillow is inserted after completing vaginal preparation for CD and before initiating skin preparation and abdominal draping. The steps for inserting the Fetal Pillow include:

1. Use the 60 mL syringe to fully deflate the Fetal Pillow and leave the cock-stop open.
2. Fold the Fetal Pillow by squeezing the firm plastic base, and with the patient’s legs in a frog-leg position, place the device in the vagina.
3. Allow the firm plastic base to open to a flat position with the base against the posterior vaginal wall and the soft silicon balloon against the fetal head.
4. Using pressure on the plastic base, gently push the Fetal Pillow posteriorly toward the sacrum of the mother.
5. Use the 60 mL syringe to inflate the balloon with 180 mL of normal saline and close the valve.
6. Straighten the patient’s legs and proceed with skin preparation and abdominal draping (FIGURE 4).

When the CD is completed, deflate the balloon by drawing out the saline with the 60 mL syringe and remove the device by hooking a finger around the firm plastic base. The Fetal Pillow is surprisingly easy to use.

Continue to: Effectiveness of the Fetal Pillow...

Effectiveness of the Fetal Pillow

In one randomized trial, 240 women undergoing CD were randomly allocated to a group in which the Fetal Pillow was placed in the vagina and inflated prior to the cesarean and a control group in which the Fetal Pillow was not used. In this study the mean length of the second stage averaged 1.9 hours.⁴ Compared with no Fetal Pillow, use of the Fetal Pillow was associated with a reduction in grade 3 extension of the uterine incision (extension into the uterine artery, vagina, or bladder) (2.5% vs 23%), a reduction in blood loss > 1,000 mL (4% vs 22%), and fewer difficult plus very difficult deliveries of the fetal head as reported by the surgeon (6% vs 39%).

In another randomized trial, 60 nulliparous women undergoing CD in the second stage of labor had a Fetal Pillow inserted in the vagina and were randomly allocated to inflation of the pillow (Fetal Pillow group) or noninflation of the pillow (control group).⁵ In this study the mean length of the second stage was 4 hours. Compared with noninflation of the Fetal Pillow, use of the inflated Fetal Pillow was associated with a reduction in grade 3 extension of the uterine incision (extensions into the uterine artery, vagina, or bladder) (0% for inflation vs 13% for noninflation) and fewer difficult plus very difficult deliveries of the fetal head as reported by the surgeon (0% for inflation vs 37% for noninflation). There was no significant difference in blood loss between the two groups (800 mL vs 900 mL). These two randomized studies both reported that the use of the Fetal Pillow was associated with a reduction in grade 3 extensions of the uterine incision and a decrease in the difficulty of delivering the fetal head.

Consider trialing the Fetal Pillow

When a CD is performed after a prolonged second stage of labor, surgical complications are common, including extensions of the uterine incision and difficulty delivering the fetal head. When a grade 3 extension occurs—with tearing of a uterine artery, deep extension into the vagina, or damage to the bladder—the surgical repair can be extraordinarily challenging. Clinical trials report that both reverse breech extraction and the Fetal Pillow can facilitate CD in the setting of a prolonged second stage. For many obstetricians reverse breech extraction is a challenging obstetric maneuver. The insertion and inflation of a Fetal Pillow is a simple procedure. Obstetrician-gynecologists learn by doing. If you have never used the Fetal Pillow, I suggest you consider trialing it in your practice. ●

Obstetricians know that a cesarean delivery (CD) for a woman with a prolonged second stage and a fetal head deeply impacted in the pelvis is challenging. In this situation, extensions of the uterine incision commonly occur, resulting in prolonged operative time and increased blood loss. Even more harrowing is the inability to deliver the fetal head, necessitating emergency assistance from other clinicians. In this situation, interventions that may be helpful include:

• extend or T the uterine incision
• enlist the aid of a clinician to push up on the fetal head with a vaginal hand (FIGURE 1)
• reverse breech extraction (FIGURE 2), and
• vaginal insertion of a Fetal Pillow prior to starting the delivery.

Evidence from clinical trials indicates that reverse breech extraction or insertion of a Fetal Pillow result in the best clinical outcomes.

Reverse breech extraction vs the push technique

Although the data are limited, most studies report that compared with pushing up with a vaginal hand (as shown in Figure 1), the reverse breech extraction technique (as shown in Figure 2) is associated with a reduction in extensions of the uterine incision, reduced blood loss, and reduced operative time.¹ In a randomized trial, 108 women with obstructed labor undergoing CD in the second stage were randomly assigned to reverse breech extraction or pushing up with a vaginal hand.² Following the uterine incision, the reverse breech extraction technique is performed by immediately reaching into the upper uterus and grasping the lower portion of the fetal leg and applying gentle traction on the leg until the second leg appeared. The lower legs are then pulled out of the uterus. Standard breech delivery maneuvers are used to deliver the shoulders and head. In the trial, compared with the push technique, reverse breech extraction was associated with fewer extensions of the uterine incision (30% vs 11%; P<.05), less blood loss (899 mL vs 1,257 mL; P<.001), and shorter operative time (56 min vs 89 min, P<.001). Fetal injury was similar with the push and breech extraction techniques (6% and 7%).

In another randomized trial, 192 women undergoing CD for obstructed labor were randomly assigned to reverse breech extraction or pushing the head up with a hand in the vagina.³ Compared with the vaginal push technique, reverse breech extraction was associated with fewer extensions of the uterine incision (19% vs 48%; P = .003), fewer cases of wound infection (2% vs 13%; P = .007), and fewer blood transfusions (2 vs 11; P = .012).

Additional options and adjuvants for facilitating delivery of a fetal head deeply impacted in the pelvis include: using a Coyne spoon, using nitroglycerine or terbutaline to relax the myometrium, breaking the vaginal suction on the fetal head before attempting delivery, keeping the wrist of the delivering hand as straight as possible to reduce uterine incision extensions, and incising the ring (if a Bandl’s ring is detected).

Continue to: The Fetal Pillow...

The Fetal Pillow

The Fetal Pillow (Safe Obstetric Systems, New York, New York) is a single-use fetal cephalic elevation device for managing the deeply impacted fetal head (FIGURE 3). The Fetal Pillow has a firm plastic base upon which is attached a soft silicon balloon. The Fetal Pillow is inserted into the vagina prior to initiating CD and the balloon is filled with 180 mL of saline, causing the fetal head to be pushed to a higher station (FIGURE 4). Use of the Fetal Pillow may be indicated prior to CD in the following situations:

• second stage labor with a deeply impacted head
• second stage labor and failed operative delivery
• occiput posterior position or deep transverse arrest
• absent progress in the first stage between 8 cm and 10 cm with a deeply impacted fetal head or excessive caput of the fetal head.

The Fetal Pillow is inserted after completing vaginal preparation for CD and before initiating skin preparation and abdominal draping. The steps for inserting the Fetal Pillow include:

1. Use the 60 mL syringe to fully deflate the Fetal Pillow and leave the cock-stop open.
2. Fold the Fetal Pillow by squeezing the firm plastic base, and with the patient’s legs in a frog-leg position, place the device in the vagina.
3. Allow the firm plastic base to open to a flat position with the base against the posterior vaginal wall and the soft silicon balloon against the fetal head.
4. Using pressure on the plastic base, gently push the Fetal Pillow posteriorly toward the sacrum of the mother.
5. Use the 60 mL syringe to inflate the balloon with 180 mL of normal saline and close the valve.
6. Straighten the patient’s legs and proceed with skin preparation and abdominal draping (FIGURE 4).

When the CD is completed, deflate the balloon by drawing out the saline with the 60 mL syringe and remove the device by hooking a finger around the firm plastic base. The Fetal Pillow is surprisingly easy to use.

Continue to: Effectiveness of the Fetal Pillow...

Effectiveness of the Fetal Pillow

In one randomized trial, 240 women undergoing CD were randomly allocated to a group in which the Fetal Pillow was placed in the vagina and inflated prior to the cesarean and a control group in which the Fetal Pillow was not used. In this study the mean length of the second stage averaged 1.9 hours.⁴ Compared with no Fetal Pillow, use of the Fetal Pillow was associated with a reduction in grade 3 extension of the uterine incision (extension into the uterine artery, vagina, or bladder) (2.5% vs 23%), a reduction in blood loss > 1,000 mL (4% vs 22%), and fewer difficult plus very difficult deliveries of the fetal head as reported by the surgeon (6% vs 39%).

In another randomized trial, 60 nulliparous women undergoing CD in the second stage of labor had a Fetal Pillow inserted in the vagina and were randomly allocated to inflation of the pillow (Fetal Pillow group) or noninflation of the pillow (control group).⁵ In this study the mean length of the second stage was 4 hours. Compared with noninflation of the Fetal Pillow, use of the inflated Fetal Pillow was associated with a reduction in grade 3 extension of the uterine incision (extensions into the uterine artery, vagina, or bladder) (0% for inflation vs 13% for noninflation) and fewer difficult plus very difficult deliveries of the fetal head as reported by the surgeon (0% for inflation vs 37% for noninflation). There was no significant difference in blood loss between the two groups (800 mL vs 900 mL). These two randomized studies both reported that the use of the Fetal Pillow was associated with a reduction in grade 3 extensions of the uterine incision and a decrease in the difficulty of delivering the fetal head.

Consider trialing the Fetal Pillow

When a CD is performed after a prolonged second stage of labor, surgical complications are common, including extensions of the uterine incision and difficulty delivering the fetal head. When a grade 3 extension occurs—with tearing of a uterine artery, deep extension into the vagina, or damage to the bladder—the surgical repair can be extraordinarily challenging. Clinical trials report that both reverse breech extraction and the Fetal Pillow can facilitate CD in the setting of a prolonged second stage. For many obstetricians reverse breech extraction is a challenging obstetric maneuver. The insertion and inflation of a Fetal Pillow is a simple procedure. Obstetrician-gynecologists learn by doing. If you have never used the Fetal Pillow, I suggest you consider trialing it in your practice. ●

The American College of Obstetricians and Gynecologists (ACOG) defines early pregnancy loss (EPL) as a nonviable, intrauterine pregnancy up to 12 6/7 weeks’ gestation.¹ The term EPL has been used interchangeably with miscarriage, spontaneous abortion, and early pregnancy failure; the preferred terms among US women who experience pregnancy loss are EPL and miscarriage.² EPL is the most common complication of early pregnancy and accounts for up to 15% to 20% of clinically recognized pregnancies.³

The most common cause of EPL is a chromosomal abnormality (TABLE 1). Other common etiologies include structural abnormalities, such as uterine fibroids or polyps. Risk factors for EPL include maternal age, prior pregnancy loss, and various maternal conditions and medication and substance use (TABLE 2).

Management options for EPL

EPL can be managed expectantly, with medication, or with uterine aspiration. These methods have different risks and benefits, and in most cases all should be made available to women who experience EPL.^5-7

Expectant management

Expectant management involves waiting for the body to spontaneously expel the nonviable pregnancy. In the absence of any signs of infection, hemodynamic instability, or other medical instability, it is safe and reasonable to wait a month or more before intervening, according to patient choice. Expectant management is up to 80% effective.⁸

Medication management

Medication management entails using mifepristone and misoprostol, or misoprostol alone, to cause uterine contractions to expel the pregnancy. A landmark study demonstrated that medication management of EPL with the combination of mifepristone and misoprostol is significantly more effective than misoprostol alone.⁹ While the mean cost of mifepristone is approximately $90 per dose, its addition is cost-effective given the increased efficacy.¹⁰

The evidence-based combination regimen is to provide mifepristone 200 mg orally, followed 24 hours later by misoprostol 800 µg vaginally, for a success rate of 87.8% by 8 days, and 91.2% by 30 days posttreatment. Success rates can be increased further by adding a second dose of misoprostol to take as needed.⁵

We strongly recommend using the combination regimen if you have access to mifepristone. If you do not have access to mifepristone in your clinical setting, perhaps this indication for use can help facilitate getting it onto your formulary. (See “Ordering mifepristone” below.)

Without access to mifepristone, medication abortion still should be offered after discussing the decreased efficacy with patients. The first-trimester misoprostol-only regimen for EPL is to give misoprostol 800 µg buccally, vaginally, or sublingually, with a second dose if there is no effect (TABLE 4).^1,5 For losses after 9 weeks, some data suggest adding additional doses of misoprostol 400 µg every 3 hours until expulsion.¹¹

Continue to: Uterine aspiration...

Uterine aspiration

Uterine aspiration is the third management option for EPL and is virtually 100% successful. Although aspiration is used when expectant or medication management fails, it is also a first-line option based on patient choice or contraindications to the other 2 management options.

We recommend either manual vacuum aspiration (MVA) or electric vacuum aspiration (EVA); sharp curettage almost never should be used. Uterine aspiration can be performed safely in a clinic, emergency department, or operating room (OR) setting, depending on patient characteristics and desires.^12-14 For various reasons, many patients prefer outpatient management. These reasons may include avoiding the costs and delays associated with OR management, wanting more control over who performs the procedure, or avoiding more significant/general anesthesia. MVA in the outpatient setting is the most cost-effective approach to uterine aspiration.¹⁵

Choosing a management approach

There are virtually no contraindications for uterine aspiration. Expectant and medication management are contraindicated (and uterine aspiration is recommended) in the setting of bleeding disorders, anticoagulation, suspected intrauterine infection, suspected molar pregnancy, significant cardiopulmonary disease, or any condition for which heavy, unsupervised bleeding might be dangerous.¹ Uterine aspiration offers immediate resolution, with a procedure usually lasting 3 to 10 minutes. By contrast, expectant and medication management offer a less predictable time to resolution and, often, a more prolonged period of active pregnancy expulsion.

In the absence of a contraindication, patient choice should determine which management option is used. All 3 options are similarly safe and effective, and the differences that do exist are acceptable to patients as long as they are allowed to access their preferred EPL management method.^5,6,16 Patient satisfaction is associated directly with the ability to choose the method of preference.

Managing pain

Pain management should be offered to all women diagnosed with EPL. Those who choose expectant or medication management likely will require only oral nonsteroidal anti-inflammatory drugs (NSAIDs). A minority may require the addition of a small number of narcotic pain pills.¹⁷

Women who choose uterine aspiration also should be offered pain management. All patients should be given a paracervical block; other medications can include NSAIDs, an oral benzodiazepine, intravenous (IV) sedation, or even general anesthesia/monitored airway care.¹⁷

Patients’ expectations about pain management should be addressed directly during initial counseling. This may help patients decide what type of management and treatment location they might prefer.

Checking blood type: Is it necessary?

The ACOG practice bulletin for EPL states, “administration of Rh D immune globulin should be considered in cases of early pregnancy loss, especially those that are later in the first trimester.”¹ A growing body of evidence indicates that Rho(D) immune globulin likely is unnecessary in early pregnancy.

A recent prospective cohort study of 42 women who were at 5 to 12 weeks’ gestation found that the fetal red blood cell concentration was below the calculated threshold for Rh sensitization.¹⁸ In light of recent evidence, the National Abortion Federation now recommends foregoing Rh testing and provision of Rh immune globulin at less than 8 weeks’ gestation for uterine aspiration and at less than 10 weeks’ gestation for medication abortion.¹⁹

We feel there is sufficient evidence to forego Rh testing in EPL at similar gestational ages, although this is not yet reflected in US societal guidelines. (It is already standard practice in some countries.) Although the risk of Rh alloimmunization is low, the risk of significant consequences in the event of Rh alloimmunization is high. Currently, it also is reasonable to continue giving Rho(D) immune globulin to Rh-negative patients who experience EPL at any gestational age. A lower dose (50 µg) is sufficient for EPL; the standard 300-µg dose also is acceptable.²⁰

We anticipate that society and ACOG guidelines will change in the next few years as the body of evidence increases, and practice should change to reflect new guidance.

Continue to: Prophylactic antibiotics...

Prophylactic antibiotics

The risk of infection with EPL is low overall regardless of the management approach.¹ Prophylactic antibiotics are recommended for patients undergoing uterine aspiration but are not necessary in the setting of expectant or medication management. We recommend prophylaxis with 1 dose of oral doxycycline 200 mg or oral azithromycin 500 mg approximately 30 minutes to 1 hour prior to uterine aspiration.²¹ Alternatives include 1 dose of oral metronidazole 500 mg or, if the patient is unable to take oral medications, IV cefazolin 2 g.

A multisite international randomized controlled trial concluded that antibiotic prophylaxis before uterine aspiration for EPL did not significantly reduce the risk of infection.²² However, there was a significant reduction in pelvic infection with antibiotic administration for the subgroup of women who underwent MVA, which is our recommended approach (along with EVA, and opposed to sharp curettage) for outpatient EPL management.

Follow-up after EPL

In-person follow-up after treatment of EPL is not medically necessary. A repeat ultrasonography 1 to 2 weeks after expectant or medication management can be helpful to confirm completion of the process, and clinicians should focus on presence or absence of a gestational sac to determine if further management is needed.¹

Follow-up by telemedicine or phone also is an option and may be preferred in the following situations:

• the patient lives far from the clinic
• travel to the clinic is difficult or expensive
• the patient has child-care issues
• there is a global pandemic necessitating physical distancing.

If the patient’s reported history and symptoms are consistent with a completed process, no further intervention is indicated.

If ongoing EPL is a concern, ask the patient to come in for an evaluation and ultrasonography. If visiting the clinic is still a challenge, following with urine or serum human chorionic gonadotropin (HCG) levels also is acceptable. Experts recommend waiting 4 weeks before expecting a negative urine HCG measurement, although up to 25% of women with a completed EPL will still have a positive test at 4 weeks.^23,24

A postprocedure serum HCG is more helpful if a preprocedure HCG level already is known. Numerous studies have evaluated phone follow-up after medication abortion and it is reasonable to translate these practices to follow-up after EPL, recognizing that direct data looking at alternative EPL follow-up are much more limited.^23,25-30

The benefit of HCG follow-up at a scheduled time (such as 1 week) is less clear for EPL than for medication abortion, as HCG trends are less predictable in the setting of EPL. However, if the pregnancy has passed, a significant drop in the HCG level would be expected. It is important to take into account the patient’s history and clinical symptoms and consider in-person evaluation with possible ultrasonography if there is concern that the pregnancy tissue has not passed.

Pay attention to mental health

It is critical to assess the patient’s mental and emotional health. This should be done both at the time of EPL diagnosis and management and again at follow-up. Both patients and their partners can struggle after experiencing EPL, and they may suffer from prolonged posttraumatic stress.³¹

Often, EPL occurs before people have shared the news about their pregnancy. This can amplify the sense of isolation and sadness many women report. Equally critical is recognizing that not all women who experience EPL grieve, and clinicians should normalize patient experiences and feelings. Provider language is important. We recommend use of these questions and phrases:

• I’m so sorry for your loss.
• How are you feeling?
• How have you been doing since I saw you last?
• Your friends/family/partner may be grieving differently or at a different pace than you—this is normal.
• Just because the EPL process is complete doesn’t necessarily mean your processing and/or grieving is over.
• Whatever you’re feeling is okay.

Continue to: Address desire for future pregnancy or contraception...

Address desire for future pregnancy or contraception

No additional workup is necessary after EPL unless a patient is experiencing recurrent pregnancy loss. We do recommend discussing plans for future conception. If a patient wants to conceive again as soon as possible, she can start trying when she feels emotionally ready (even before her next menstrual period). One study found that the ability to conceive and those pregnancy outcomes were the same when patients were randomly assigned to start trying immediately versus waiting 3 months after EPL.³²

Alternatively, a patient may want to prevent pregnancy after EPL, and this information should be explicitly elicited and addressed with comprehensive contraception counseling as needed. All forms of contraception can be initiated immediately on successful management of EPL. All contraceptive methods, including an intrauterine device, can be initiated immediately following uterine aspiration.^1,33,34

Patients should be reminded that if they delay contraception initiation by more than 7 days, they are potentially at risk for pregnancy.³⁵ Most importantly, clinicians should not make assumptions about future pregnancy desires and should ask open-ended questions to provide appropriate patient counseling.

Finally, patients may feel additional anxiety in a subsequent pregnancy. It is helpful to acknowledge this and perhaps even offer earlier and more frequent visits in early pregnancy to help reduce anxiety. EPL is commonly experienced, and unfortunately it is sometimes poorly addressed by clinicians.

We hope this guidance will help you provide excellent, evidence-based, and sensitive care that will not only manage your patient’s EPL but also make the experience as positive as possible. ●

The American College of Obstetricians and Gynecologists (ACOG) defines early pregnancy loss (EPL) as a nonviable, intrauterine pregnancy up to 12 6/7 weeks’ gestation.¹ The term EPL has been used interchangeably with miscarriage, spontaneous abortion, and early pregnancy failure; the preferred terms among US women who experience pregnancy loss are EPL and miscarriage.² EPL is the most common complication of early pregnancy and accounts for up to 15% to 20% of clinically recognized pregnancies.³

The most common cause of EPL is a chromosomal abnormality (TABLE 1). Other common etiologies include structural abnormalities, such as uterine fibroids or polyps. Risk factors for EPL include maternal age, prior pregnancy loss, and various maternal conditions and medication and substance use (TABLE 2).

Management options for EPL

EPL can be managed expectantly, with medication, or with uterine aspiration. These methods have different risks and benefits, and in most cases all should be made available to women who experience EPL.^5-7

Expectant management

Expectant management involves waiting for the body to spontaneously expel the nonviable pregnancy. In the absence of any signs of infection, hemodynamic instability, or other medical instability, it is safe and reasonable to wait a month or more before intervening, according to patient choice. Expectant management is up to 80% effective.⁸

Medication management

Medication management entails using mifepristone and misoprostol, or misoprostol alone, to cause uterine contractions to expel the pregnancy. A landmark study demonstrated that medication management of EPL with the combination of mifepristone and misoprostol is significantly more effective than misoprostol alone.⁹ While the mean cost of mifepristone is approximately $90 per dose, its addition is cost-effective given the increased efficacy.¹⁰

The evidence-based combination regimen is to provide mifepristone 200 mg orally, followed 24 hours later by misoprostol 800 µg vaginally, for a success rate of 87.8% by 8 days, and 91.2% by 30 days posttreatment. Success rates can be increased further by adding a second dose of misoprostol to take as needed.⁵

We strongly recommend using the combination regimen if you have access to mifepristone. If you do not have access to mifepristone in your clinical setting, perhaps this indication for use can help facilitate getting it onto your formulary. (See “Ordering mifepristone” below.)

Without access to mifepristone, medication abortion still should be offered after discussing the decreased efficacy with patients. The first-trimester misoprostol-only regimen for EPL is to give misoprostol 800 µg buccally, vaginally, or sublingually, with a second dose if there is no effect (TABLE 4).^1,5 For losses after 9 weeks, some data suggest adding additional doses of misoprostol 400 µg every 3 hours until expulsion.¹¹

Continue to: Uterine aspiration...

Uterine aspiration

Uterine aspiration is the third management option for EPL and is virtually 100% successful. Although aspiration is used when expectant or medication management fails, it is also a first-line option based on patient choice or contraindications to the other 2 management options.

We recommend either manual vacuum aspiration (MVA) or electric vacuum aspiration (EVA); sharp curettage almost never should be used. Uterine aspiration can be performed safely in a clinic, emergency department, or operating room (OR) setting, depending on patient characteristics and desires.^12-14 For various reasons, many patients prefer outpatient management. These reasons may include avoiding the costs and delays associated with OR management, wanting more control over who performs the procedure, or avoiding more significant/general anesthesia. MVA in the outpatient setting is the most cost-effective approach to uterine aspiration.¹⁵

Choosing a management approach

There are virtually no contraindications for uterine aspiration. Expectant and medication management are contraindicated (and uterine aspiration is recommended) in the setting of bleeding disorders, anticoagulation, suspected intrauterine infection, suspected molar pregnancy, significant cardiopulmonary disease, or any condition for which heavy, unsupervised bleeding might be dangerous.¹ Uterine aspiration offers immediate resolution, with a procedure usually lasting 3 to 10 minutes. By contrast, expectant and medication management offer a less predictable time to resolution and, often, a more prolonged period of active pregnancy expulsion.

In the absence of a contraindication, patient choice should determine which management option is used. All 3 options are similarly safe and effective, and the differences that do exist are acceptable to patients as long as they are allowed to access their preferred EPL management method.^5,6,16 Patient satisfaction is associated directly with the ability to choose the method of preference.

Managing pain

Pain management should be offered to all women diagnosed with EPL. Those who choose expectant or medication management likely will require only oral nonsteroidal anti-inflammatory drugs (NSAIDs). A minority may require the addition of a small number of narcotic pain pills.¹⁷

Women who choose uterine aspiration also should be offered pain management. All patients should be given a paracervical block; other medications can include NSAIDs, an oral benzodiazepine, intravenous (IV) sedation, or even general anesthesia/monitored airway care.¹⁷

Patients’ expectations about pain management should be addressed directly during initial counseling. This may help patients decide what type of management and treatment location they might prefer.

Checking blood type: Is it necessary?

The ACOG practice bulletin for EPL states, “administration of Rh D immune globulin should be considered in cases of early pregnancy loss, especially those that are later in the first trimester.”¹ A growing body of evidence indicates that Rho(D) immune globulin likely is unnecessary in early pregnancy.

A recent prospective cohort study of 42 women who were at 5 to 12 weeks’ gestation found that the fetal red blood cell concentration was below the calculated threshold for Rh sensitization.¹⁸ In light of recent evidence, the National Abortion Federation now recommends foregoing Rh testing and provision of Rh immune globulin at less than 8 weeks’ gestation for uterine aspiration and at less than 10 weeks’ gestation for medication abortion.¹⁹

We feel there is sufficient evidence to forego Rh testing in EPL at similar gestational ages, although this is not yet reflected in US societal guidelines. (It is already standard practice in some countries.) Although the risk of Rh alloimmunization is low, the risk of significant consequences in the event of Rh alloimmunization is high. Currently, it also is reasonable to continue giving Rho(D) immune globulin to Rh-negative patients who experience EPL at any gestational age. A lower dose (50 µg) is sufficient for EPL; the standard 300-µg dose also is acceptable.²⁰

We anticipate that society and ACOG guidelines will change in the next few years as the body of evidence increases, and practice should change to reflect new guidance.

Continue to: Prophylactic antibiotics...

Prophylactic antibiotics

The risk of infection with EPL is low overall regardless of the management approach.¹ Prophylactic antibiotics are recommended for patients undergoing uterine aspiration but are not necessary in the setting of expectant or medication management. We recommend prophylaxis with 1 dose of oral doxycycline 200 mg or oral azithromycin 500 mg approximately 30 minutes to 1 hour prior to uterine aspiration.²¹ Alternatives include 1 dose of oral metronidazole 500 mg or, if the patient is unable to take oral medications, IV cefazolin 2 g.

A multisite international randomized controlled trial concluded that antibiotic prophylaxis before uterine aspiration for EPL did not significantly reduce the risk of infection.²² However, there was a significant reduction in pelvic infection with antibiotic administration for the subgroup of women who underwent MVA, which is our recommended approach (along with EVA, and opposed to sharp curettage) for outpatient EPL management.

Follow-up after EPL

In-person follow-up after treatment of EPL is not medically necessary. A repeat ultrasonography 1 to 2 weeks after expectant or medication management can be helpful to confirm completion of the process, and clinicians should focus on presence or absence of a gestational sac to determine if further management is needed.¹

Follow-up by telemedicine or phone also is an option and may be preferred in the following situations:

• the patient lives far from the clinic
• travel to the clinic is difficult or expensive
• the patient has child-care issues
• there is a global pandemic necessitating physical distancing.

If the patient’s reported history and symptoms are consistent with a completed process, no further intervention is indicated.

If ongoing EPL is a concern, ask the patient to come in for an evaluation and ultrasonography. If visiting the clinic is still a challenge, following with urine or serum human chorionic gonadotropin (HCG) levels also is acceptable. Experts recommend waiting 4 weeks before expecting a negative urine HCG measurement, although up to 25% of women with a completed EPL will still have a positive test at 4 weeks.^23,24

A postprocedure serum HCG is more helpful if a preprocedure HCG level already is known. Numerous studies have evaluated phone follow-up after medication abortion and it is reasonable to translate these practices to follow-up after EPL, recognizing that direct data looking at alternative EPL follow-up are much more limited.^23,25-30

The benefit of HCG follow-up at a scheduled time (such as 1 week) is less clear for EPL than for medication abortion, as HCG trends are less predictable in the setting of EPL. However, if the pregnancy has passed, a significant drop in the HCG level would be expected. It is important to take into account the patient’s history and clinical symptoms and consider in-person evaluation with possible ultrasonography if there is concern that the pregnancy tissue has not passed.

Pay attention to mental health

It is critical to assess the patient’s mental and emotional health. This should be done both at the time of EPL diagnosis and management and again at follow-up. Both patients and their partners can struggle after experiencing EPL, and they may suffer from prolonged posttraumatic stress.³¹

Often, EPL occurs before people have shared the news about their pregnancy. This can amplify the sense of isolation and sadness many women report. Equally critical is recognizing that not all women who experience EPL grieve, and clinicians should normalize patient experiences and feelings. Provider language is important. We recommend use of these questions and phrases:

• I’m so sorry for your loss.
• How are you feeling?
• How have you been doing since I saw you last?
• Your friends/family/partner may be grieving differently or at a different pace than you—this is normal.
• Just because the EPL process is complete doesn’t necessarily mean your processing and/or grieving is over.
• Whatever you’re feeling is okay.

Continue to: Address desire for future pregnancy or contraception...

Address desire for future pregnancy or contraception

No additional workup is necessary after EPL unless a patient is experiencing recurrent pregnancy loss. We do recommend discussing plans for future conception. If a patient wants to conceive again as soon as possible, she can start trying when she feels emotionally ready (even before her next menstrual period). One study found that the ability to conceive and those pregnancy outcomes were the same when patients were randomly assigned to start trying immediately versus waiting 3 months after EPL.³²

Alternatively, a patient may want to prevent pregnancy after EPL, and this information should be explicitly elicited and addressed with comprehensive contraception counseling as needed. All forms of contraception can be initiated immediately on successful management of EPL. All contraceptive methods, including an intrauterine device, can be initiated immediately following uterine aspiration.^1,33,34

Patients should be reminded that if they delay contraception initiation by more than 7 days, they are potentially at risk for pregnancy.³⁵ Most importantly, clinicians should not make assumptions about future pregnancy desires and should ask open-ended questions to provide appropriate patient counseling.

Finally, patients may feel additional anxiety in a subsequent pregnancy. It is helpful to acknowledge this and perhaps even offer earlier and more frequent visits in early pregnancy to help reduce anxiety. EPL is commonly experienced, and unfortunately it is sometimes poorly addressed by clinicians.

We hope this guidance will help you provide excellent, evidence-based, and sensitive care that will not only manage your patient’s EPL but also make the experience as positive as possible. ●

The American College of Obstetricians and Gynecologists (ACOG) defines early pregnancy loss (EPL) as a nonviable, intrauterine pregnancy up to 12 6/7 weeks’ gestation.¹ The term EPL has been used interchangeably with miscarriage, spontaneous abortion, and early pregnancy failure; the preferred terms among US women who experience pregnancy loss are EPL and miscarriage.² EPL is the most common complication of early pregnancy and accounts for up to 15% to 20% of clinically recognized pregnancies.³

The most common cause of EPL is a chromosomal abnormality (TABLE 1). Other common etiologies include structural abnormalities, such as uterine fibroids or polyps. Risk factors for EPL include maternal age, prior pregnancy loss, and various maternal conditions and medication and substance use (TABLE 2).

Management options for EPL

EPL can be managed expectantly, with medication, or with uterine aspiration. These methods have different risks and benefits, and in most cases all should be made available to women who experience EPL.^5-7

Expectant management

Expectant management involves waiting for the body to spontaneously expel the nonviable pregnancy. In the absence of any signs of infection, hemodynamic instability, or other medical instability, it is safe and reasonable to wait a month or more before intervening, according to patient choice. Expectant management is up to 80% effective.⁸

Medication management

Medication management entails using mifepristone and misoprostol, or misoprostol alone, to cause uterine contractions to expel the pregnancy. A landmark study demonstrated that medication management of EPL with the combination of mifepristone and misoprostol is significantly more effective than misoprostol alone.⁹ While the mean cost of mifepristone is approximately $90 per dose, its addition is cost-effective given the increased efficacy.¹⁰

The evidence-based combination regimen is to provide mifepristone 200 mg orally, followed 24 hours later by misoprostol 800 µg vaginally, for a success rate of 87.8% by 8 days, and 91.2% by 30 days posttreatment. Success rates can be increased further by adding a second dose of misoprostol to take as needed.⁵

We strongly recommend using the combination regimen if you have access to mifepristone. If you do not have access to mifepristone in your clinical setting, perhaps this indication for use can help facilitate getting it onto your formulary. (See “Ordering mifepristone” below.)

Without access to mifepristone, medication abortion still should be offered after discussing the decreased efficacy with patients. The first-trimester misoprostol-only regimen for EPL is to give misoprostol 800 µg buccally, vaginally, or sublingually, with a second dose if there is no effect (TABLE 4).^1,5 For losses after 9 weeks, some data suggest adding additional doses of misoprostol 400 µg every 3 hours until expulsion.¹¹

Continue to: Uterine aspiration...

Uterine aspiration

Uterine aspiration is the third management option for EPL and is virtually 100% successful. Although aspiration is used when expectant or medication management fails, it is also a first-line option based on patient choice or contraindications to the other 2 management options.

We recommend either manual vacuum aspiration (MVA) or electric vacuum aspiration (EVA); sharp curettage almost never should be used. Uterine aspiration can be performed safely in a clinic, emergency department, or operating room (OR) setting, depending on patient characteristics and desires.^12-14 For various reasons, many patients prefer outpatient management. These reasons may include avoiding the costs and delays associated with OR management, wanting more control over who performs the procedure, or avoiding more significant/general anesthesia. MVA in the outpatient setting is the most cost-effective approach to uterine aspiration.¹⁵

Choosing a management approach

There are virtually no contraindications for uterine aspiration. Expectant and medication management are contraindicated (and uterine aspiration is recommended) in the setting of bleeding disorders, anticoagulation, suspected intrauterine infection, suspected molar pregnancy, significant cardiopulmonary disease, or any condition for which heavy, unsupervised bleeding might be dangerous.¹ Uterine aspiration offers immediate resolution, with a procedure usually lasting 3 to 10 minutes. By contrast, expectant and medication management offer a less predictable time to resolution and, often, a more prolonged period of active pregnancy expulsion.

In the absence of a contraindication, patient choice should determine which management option is used. All 3 options are similarly safe and effective, and the differences that do exist are acceptable to patients as long as they are allowed to access their preferred EPL management method.^5,6,16 Patient satisfaction is associated directly with the ability to choose the method of preference.

Managing pain

Pain management should be offered to all women diagnosed with EPL. Those who choose expectant or medication management likely will require only oral nonsteroidal anti-inflammatory drugs (NSAIDs). A minority may require the addition of a small number of narcotic pain pills.¹⁷

Women who choose uterine aspiration also should be offered pain management. All patients should be given a paracervical block; other medications can include NSAIDs, an oral benzodiazepine, intravenous (IV) sedation, or even general anesthesia/monitored airway care.¹⁷

Patients’ expectations about pain management should be addressed directly during initial counseling. This may help patients decide what type of management and treatment location they might prefer.

Checking blood type: Is it necessary?

The ACOG practice bulletin for EPL states, “administration of Rh D immune globulin should be considered in cases of early pregnancy loss, especially those that are later in the first trimester.”¹ A growing body of evidence indicates that Rho(D) immune globulin likely is unnecessary in early pregnancy.

A recent prospective cohort study of 42 women who were at 5 to 12 weeks’ gestation found that the fetal red blood cell concentration was below the calculated threshold for Rh sensitization.¹⁸ In light of recent evidence, the National Abortion Federation now recommends foregoing Rh testing and provision of Rh immune globulin at less than 8 weeks’ gestation for uterine aspiration and at less than 10 weeks’ gestation for medication abortion.¹⁹

We feel there is sufficient evidence to forego Rh testing in EPL at similar gestational ages, although this is not yet reflected in US societal guidelines. (It is already standard practice in some countries.) Although the risk of Rh alloimmunization is low, the risk of significant consequences in the event of Rh alloimmunization is high. Currently, it also is reasonable to continue giving Rho(D) immune globulin to Rh-negative patients who experience EPL at any gestational age. A lower dose (50 µg) is sufficient for EPL; the standard 300-µg dose also is acceptable.²⁰

We anticipate that society and ACOG guidelines will change in the next few years as the body of evidence increases, and practice should change to reflect new guidance.

Continue to: Prophylactic antibiotics...

Prophylactic antibiotics

The risk of infection with EPL is low overall regardless of the management approach.¹ Prophylactic antibiotics are recommended for patients undergoing uterine aspiration but are not necessary in the setting of expectant or medication management. We recommend prophylaxis with 1 dose of oral doxycycline 200 mg or oral azithromycin 500 mg approximately 30 minutes to 1 hour prior to uterine aspiration.²¹ Alternatives include 1 dose of oral metronidazole 500 mg or, if the patient is unable to take oral medications, IV cefazolin 2 g.

A multisite international randomized controlled trial concluded that antibiotic prophylaxis before uterine aspiration for EPL did not significantly reduce the risk of infection.²² However, there was a significant reduction in pelvic infection with antibiotic administration for the subgroup of women who underwent MVA, which is our recommended approach (along with EVA, and opposed to sharp curettage) for outpatient EPL management.

Follow-up after EPL

In-person follow-up after treatment of EPL is not medically necessary. A repeat ultrasonography 1 to 2 weeks after expectant or medication management can be helpful to confirm completion of the process, and clinicians should focus on presence or absence of a gestational sac to determine if further management is needed.¹

Follow-up by telemedicine or phone also is an option and may be preferred in the following situations:

• the patient lives far from the clinic
• travel to the clinic is difficult or expensive
• the patient has child-care issues
• there is a global pandemic necessitating physical distancing.

If the patient’s reported history and symptoms are consistent with a completed process, no further intervention is indicated.

If ongoing EPL is a concern, ask the patient to come in for an evaluation and ultrasonography. If visiting the clinic is still a challenge, following with urine or serum human chorionic gonadotropin (HCG) levels also is acceptable. Experts recommend waiting 4 weeks before expecting a negative urine HCG measurement, although up to 25% of women with a completed EPL will still have a positive test at 4 weeks.^23,24

A postprocedure serum HCG is more helpful if a preprocedure HCG level already is known. Numerous studies have evaluated phone follow-up after medication abortion and it is reasonable to translate these practices to follow-up after EPL, recognizing that direct data looking at alternative EPL follow-up are much more limited.^23,25-30

The benefit of HCG follow-up at a scheduled time (such as 1 week) is less clear for EPL than for medication abortion, as HCG trends are less predictable in the setting of EPL. However, if the pregnancy has passed, a significant drop in the HCG level would be expected. It is important to take into account the patient’s history and clinical symptoms and consider in-person evaluation with possible ultrasonography if there is concern that the pregnancy tissue has not passed.

Pay attention to mental health

It is critical to assess the patient’s mental and emotional health. This should be done both at the time of EPL diagnosis and management and again at follow-up. Both patients and their partners can struggle after experiencing EPL, and they may suffer from prolonged posttraumatic stress.³¹

Often, EPL occurs before people have shared the news about their pregnancy. This can amplify the sense of isolation and sadness many women report. Equally critical is recognizing that not all women who experience EPL grieve, and clinicians should normalize patient experiences and feelings. Provider language is important. We recommend use of these questions and phrases:

• I’m so sorry for your loss.
• How are you feeling?
• How have you been doing since I saw you last?
• Your friends/family/partner may be grieving differently or at a different pace than you—this is normal.
• Just because the EPL process is complete doesn’t necessarily mean your processing and/or grieving is over.
• Whatever you’re feeling is okay.

Continue to: Address desire for future pregnancy or contraception...

Address desire for future pregnancy or contraception

No additional workup is necessary after EPL unless a patient is experiencing recurrent pregnancy loss. We do recommend discussing plans for future conception. If a patient wants to conceive again as soon as possible, she can start trying when she feels emotionally ready (even before her next menstrual period). One study found that the ability to conceive and those pregnancy outcomes were the same when patients were randomly assigned to start trying immediately versus waiting 3 months after EPL.³²

Alternatively, a patient may want to prevent pregnancy after EPL, and this information should be explicitly elicited and addressed with comprehensive contraception counseling as needed. All forms of contraception can be initiated immediately on successful management of EPL. All contraceptive methods, including an intrauterine device, can be initiated immediately following uterine aspiration.^1,33,34

Patients should be reminded that if they delay contraception initiation by more than 7 days, they are potentially at risk for pregnancy.³⁵ Most importantly, clinicians should not make assumptions about future pregnancy desires and should ask open-ended questions to provide appropriate patient counseling.

Finally, patients may feel additional anxiety in a subsequent pregnancy. It is helpful to acknowledge this and perhaps even offer earlier and more frequent visits in early pregnancy to help reduce anxiety. EPL is commonly experienced, and unfortunately it is sometimes poorly addressed by clinicians.

We hope this guidance will help you provide excellent, evidence-based, and sensitive care that will not only manage your patient’s EPL but also make the experience as positive as possible. ●

In the first 2 articles of this series, “Telemedicine: A primer for today’s ObGyn” and “Telemedicine: Common hurdles and proper coding for ObGyns,” which appeared in the May and June issues of OBG Management, we discussed caring for patients without face-to-face visits and that virtual visits are an opportunity to provide good care in a world such as that created by COVID-19. We also discussed which patients are the most appropriate candidates for telemedicine, as well as how to properly code virtual visits so that you are paid for your time and service. This third article addresses the legal concerns and caveats of using telemedicine and makes a prediction for the future of virtual health care.

Legal issues surrounding telemedicine

There are numerous legal, regulatory, and compliance issues that existed before the pandemic that likely will continue to be of concern postpandemic. Although the recent 1135 waiver (allowing Medicare to pay for office, hospital, and other visits furnished via telehealth)¹ and other regulations are now in place for almost every aspect of telemedicine, virtual medicine is not a free-for-all (even though it may seem like it). Practicing ethical telemedicine entails abiding by numerous federal and state-specific laws and requirements. It is important to be aware of the laws in each state in which your patients are located and to practice according to the requirements of these laws. This often requires consultation with an experienced health care attorney who is knowledgeable about the use of telemedicine and who can help you with issues surrounding:

• Malpractice insurance. It is an important first step to contact your practice’s malpractice insurance carrier and confirm coverage for telemedicine visits. Telemedicine visits are considered the same as in-person visits when determining scope of practice and malpractice liability. Nevertheless, a best practice is to have written verification from your malpractice carrier about the types of telemedicine services and claims for which your ObGyn practice is covered. Additionally, if you care for patients virtually who live in a state in which you are not licensed, check with your carrier to determine if potential claims will be covered.
• Corporate practice laws. These laws require that your practice be governed by a health care professional and not someone with a nonmedical background. This becomes important if you are looking to create a virtual practice in another state. States that prohibit the corporate practice of medicine have state-specific mandates that require strict adherence. Consult with a health care attorney before entering into a business arrangement with a nonphysician or corporate entity.
• Delegation agreement requirements. These laws require physician collaboration and/or supervision of allied health care workers such as nurse practitioners (NPs) and physician assistants (PAs) and may limit the number of allied health care providers that a physician may supervise. Many states are allowing allied health care workers to practice at the top of their license, but this is still state specific. Thus, it is an important issue to consider, especially for practices that rely heavily on the services of advanced practice registered nurses (APRNs), for example, who have a broad scope of practice and who may be qualified to care for many common ObGyn problems.
• Informed consent requirements. Some states have no requirements regarding consent for a virtual visit. Others require either written or verbal consent. In states that do not require informed consent, it is best practice to nevertheless obtain either written or oral consent and to document in the patient’s record that consent was obtained before initiating a virtual visit. The consent should follow state-mandated disclosures, as well as the practice’s policies regarding billing, scheduling, and cancellations of telemedicine visits.
• Interstate licensing laws. Because of the COVID-19 pandemic, federal and state licensure waivers are in place to allow physicians to care for patients outside the physician’s home state, but these waivers likely will be lifted postpandemic. Once waivers are lifted, physicians will need to be licensed not only in the state in which they practice but also in the state where the patient is located at the time of treatment. Even physicians who practice in states that belong to the Interstate Medical Licensure Compact² must apply for and obtain a license to practice within Compact member states. Membership in the Interstate Medical Licensure Compact expedites the licensure process, but does not alleviate the need to obtain a license to practice in each member state. To ensure compliance with interstate licensure laws, seek advice from a health care attorney specializing in telemedicine.
• Drug monitoring laws. The Ryan Haight Online Pharmacy Consumer Protection Act of 2008³ implemented a requirement that physicians have at least one in-person, face-to-face visit with patients before prescribing a controlled substance for the first time. Because state laws may vary, we suggest consulting with a health care attorney to understand your state’s requirements for prescribing controlled substances to new patients and when using telemedicine (see “Prescription drugs” at https://www.cdc.gov/phlp/publications/topic/prescription.html for more information).
• Data privacy and security. From a content perspective, health care data and personally identifiable information are extremely rich, which makes electronic health records (EHRs), or the digital form of patients’ medical histories and other data, particularly tempting targets for hackers and cyber criminals. We caution that services such as Facetime and Skype are not encrypted; they have been granted waivers for telemedicine use, but these waivers are probably not going to be permanent once the COVID-19 crisis passes.
• HIPAA compliance. Generally—and certainly under normal circumstances—telemedicine is subject to the same rules governing protected health information (PHI) as any other technology and process used in physician practices. The Health Insurance Portability and Accountability Act (HIPAA) Security Rule includes guidelines on telemedicine and stipulates that only authorized users should have access to ePHI, that a system of secure communication must be established to protect the security of ePHI, and that a system to monitor communications must be maintained, among other requirements.⁴ Third parties that provide telemedicine, data storage, and other services, with a few exceptions, must have a business associate agreement (BAA) with a covered entity. Covered entities include health care providers, health plans, and health and health care clearinghouses. Such an agreement should include specific language that ensures that HIPAA requirements will be met and that governs permitted and required uses of PHI, strictly limits other uses of PHI, and establishes appropriate safeguards and steps that must be taken in the event of a breach or disallowed disclosure of PHI. Best practice requires that providers establish robust protocols, policies, and processes for handling sensitive information.

During the COVID-19 pandemic, however, certain HIPAA restrictions relating to telemedicine have been temporarily waived by the US Department of Health and Human Services (HHS). More specifically, HHS Secretary Alex Azar has exercised his authority to waive sanctions against covered hospitals for noncompliance with requirements: to obtain a patient’s consent to speak with family members or friends involved in the patient’s care, to distribute a notice of privacy practices, to request privacy restrictions, to request confidential communications, and the use of nonpublic facing audio and video communications products, among others.⁵ These are temporary measures only; once the national public health emergency has passed or at the HHS Secretary’s discretion based on new developments, this position on discretionary nonenforcement may end.

Continue to: Crisis creates opportunity: The future of telemedicine...

Crisis creates opportunity: The future of telemedicine

It was just a few years ago when the use of telemedicine was relegated to treating patients in only rural areas or those located a great distance from brick and mortar practices. But the pandemic, along with the coincident relaxation of the Centers for Medicare and Medicaid Services’ (CMS) requirements for conducting telemedicine visits has made the technology highly attractive to ObGyns who can now treat many patients 24/7 from their homes using laptops and even mobile devices. In addition, the pandemic has prompted an expansion of current procedural terminology (CPT) codes that makes it possible to bill patients for telemedicine services and be appropriately compensated.

Thus, as awful as COVID-19 is, we can conclude that it has provided us with opportunities. We predict that when the crisis has abated, although the current relaxation of HIPAA guidelines will probably be rescinded, restrictions will not likely return to precoronavirus status; changes will certainly be made, and telemedicine will likely become part and parcel of caring for ObGyn patients.

Telemedicine has been used successfully for years to improve patient access to medical care while reducing health care costs. In 2016, an estimated 61% of US health care institutions and 40% to 50% of US hospitals used telemedicine.⁶ And according to the results of a survey of America’s physicians conducted in April 2020, almost half (48%) are treating patients through telemedicine, which is up from just 18% 2 years ago.⁷

Letting loose the genie in the bottle

Widespread use of telemedicine traditionally has been limited by low reimbursement rates and interstate licensing and practice issues, but we predict that the use of telemedicine is going to significantly increase in the future. Here’s why:⁸ Disruptive innovation was defined by Professor Clayton Christensen of the Harvard Business School in 1997.⁹ Disruptive innovation explains the process by which a disruptive force spurs the development of simple, convenient, and affordable solutions that then replace processes that are expensive and complicated. According to Christensen, a critical element of the process is a technology that makes a product or service more accessible to a larger number of people while reducing cost and increasing ease of use. For example, innovations making equipment for dialysis cheaper and simpler helped make it possible to administer the treatment in neighborhood clinics, rather than in centralized hospitals, thus disrupting the hospital’s share of the dialysis business.

The concept of telemedicine and the technology for its implementation have been available for more than 15 years. However, it was the coronavirus that released the genie from the bottle, serving as the disruptive force to release the innovation. Telemedicine has demonstrated that the technology offers solutions that address patients’ urgent, unmet needs for access to care at an affordable price and that enhances the productivity of the ObGyn. The result is simple, convenient, and affordable; patients can readily access the medical care they need to effectively maintain their health or manage conditions that arise.

Telemedicine has reached a level of critical mass. Data suggest that patients, especially younger ones, have accepted and appreciate the use of this technology.¹⁰ It gives patients more opportunities to receive health care in their homes or at work where they feel more comfortable and less anxious than they do in physicians’ offices.

Several other health care issues may be altered by telemedicine.

The physician shortage. If the data are to be believed, there will be a significant shortage of physicians—and perhaps ObGyns—in the near future.¹¹ Telemedicine can help the problem by making it possible to provide medical care not only in rural areas where there are no ObGyns but also in urban areas where a shortage may be looming.

Continuing medical education (CME). CME is moving from large, expensive, in-person conferences to virtual conferences and online learning.

The American health care budget is bloated with expenses exceeding $3 trillion.¹² Telemedicine can help reduce health care costs by facilitating patient appointments that do not require office staff or many of the overhead expenses associated with brick and mortar operations. Telemedicine reduces the financial impact of patient no-shows. Because patients are keen on participating, the use of telemedicine likely will improve patient engagement and clinical outcomes. Telemedicine already has a reputation of reducing unnecessary office and emergency room visits and hospital admissions.¹³

Clinical trials. One of the obstacles to overcome in the early stages of a clinical trial is finding participants. Telemedicine will make patient recruitment more straightforward. And because telemedicine makes distance from the office a nonissue, recruiters will be less restricted by geographic boundaries.

In addition, telemedicine allows for the participants of the trial to stay in their homes most of the time while wearing remote monitoring devices. Such devices would enable trial researchers to spot deviations from patients’ baseline readings.

The bottom line

COVID-19 has provided the opportunity for us to see how telemedicine can contribute to reducing the spread of infectious diseases by protecting physicians, their staff, and patients themselves. Once the COVID-19 crisis has passed, it is likely that telemedicine will continue to move health care delivery from the hospital or clinic into the home. The growth and integration of information and communication technologies into health care delivery holds great potential for patients, providers, and payers in health systems of the future. ●

In the first 2 articles of this series, “Telemedicine: A primer for today’s ObGyn” and “Telemedicine: Common hurdles and proper coding for ObGyns,” which appeared in the May and June issues of OBG Management, we discussed caring for patients without face-to-face visits and that virtual visits are an opportunity to provide good care in a world such as that created by COVID-19. We also discussed which patients are the most appropriate candidates for telemedicine, as well as how to properly code virtual visits so that you are paid for your time and service. This third article addresses the legal concerns and caveats of using telemedicine and makes a prediction for the future of virtual health care.

Legal issues surrounding telemedicine

There are numerous legal, regulatory, and compliance issues that existed before the pandemic that likely will continue to be of concern postpandemic. Although the recent 1135 waiver (allowing Medicare to pay for office, hospital, and other visits furnished via telehealth)¹ and other regulations are now in place for almost every aspect of telemedicine, virtual medicine is not a free-for-all (even though it may seem like it). Practicing ethical telemedicine entails abiding by numerous federal and state-specific laws and requirements. It is important to be aware of the laws in each state in which your patients are located and to practice according to the requirements of these laws. This often requires consultation with an experienced health care attorney who is knowledgeable about the use of telemedicine and who can help you with issues surrounding:

• Malpractice insurance. It is an important first step to contact your practice’s malpractice insurance carrier and confirm coverage for telemedicine visits. Telemedicine visits are considered the same as in-person visits when determining scope of practice and malpractice liability. Nevertheless, a best practice is to have written verification from your malpractice carrier about the types of telemedicine services and claims for which your ObGyn practice is covered. Additionally, if you care for patients virtually who live in a state in which you are not licensed, check with your carrier to determine if potential claims will be covered.
• Corporate practice laws. These laws require that your practice be governed by a health care professional and not someone with a nonmedical background. This becomes important if you are looking to create a virtual practice in another state. States that prohibit the corporate practice of medicine have state-specific mandates that require strict adherence. Consult with a health care attorney before entering into a business arrangement with a nonphysician or corporate entity.
• Delegation agreement requirements. These laws require physician collaboration and/or supervision of allied health care workers such as nurse practitioners (NPs) and physician assistants (PAs) and may limit the number of allied health care providers that a physician may supervise. Many states are allowing allied health care workers to practice at the top of their license, but this is still state specific. Thus, it is an important issue to consider, especially for practices that rely heavily on the services of advanced practice registered nurses (APRNs), for example, who have a broad scope of practice and who may be qualified to care for many common ObGyn problems.
• Informed consent requirements. Some states have no requirements regarding consent for a virtual visit. Others require either written or verbal consent. In states that do not require informed consent, it is best practice to nevertheless obtain either written or oral consent and to document in the patient’s record that consent was obtained before initiating a virtual visit. The consent should follow state-mandated disclosures, as well as the practice’s policies regarding billing, scheduling, and cancellations of telemedicine visits.
• Interstate licensing laws. Because of the COVID-19 pandemic, federal and state licensure waivers are in place to allow physicians to care for patients outside the physician’s home state, but these waivers likely will be lifted postpandemic. Once waivers are lifted, physicians will need to be licensed not only in the state in which they practice but also in the state where the patient is located at the time of treatment. Even physicians who practice in states that belong to the Interstate Medical Licensure Compact² must apply for and obtain a license to practice within Compact member states. Membership in the Interstate Medical Licensure Compact expedites the licensure process, but does not alleviate the need to obtain a license to practice in each member state. To ensure compliance with interstate licensure laws, seek advice from a health care attorney specializing in telemedicine.
• Drug monitoring laws. The Ryan Haight Online Pharmacy Consumer Protection Act of 2008³ implemented a requirement that physicians have at least one in-person, face-to-face visit with patients before prescribing a controlled substance for the first time. Because state laws may vary, we suggest consulting with a health care attorney to understand your state’s requirements for prescribing controlled substances to new patients and when using telemedicine (see “Prescription drugs” at https://www.cdc.gov/phlp/publications/topic/prescription.html for more information).
• Data privacy and security. From a content perspective, health care data and personally identifiable information are extremely rich, which makes electronic health records (EHRs), or the digital form of patients’ medical histories and other data, particularly tempting targets for hackers and cyber criminals. We caution that services such as Facetime and Skype are not encrypted; they have been granted waivers for telemedicine use, but these waivers are probably not going to be permanent once the COVID-19 crisis passes.
• HIPAA compliance. Generally—and certainly under normal circumstances—telemedicine is subject to the same rules governing protected health information (PHI) as any other technology and process used in physician practices. The Health Insurance Portability and Accountability Act (HIPAA) Security Rule includes guidelines on telemedicine and stipulates that only authorized users should have access to ePHI, that a system of secure communication must be established to protect the security of ePHI, and that a system to monitor communications must be maintained, among other requirements.⁴ Third parties that provide telemedicine, data storage, and other services, with a few exceptions, must have a business associate agreement (BAA) with a covered entity. Covered entities include health care providers, health plans, and health and health care clearinghouses. Such an agreement should include specific language that ensures that HIPAA requirements will be met and that governs permitted and required uses of PHI, strictly limits other uses of PHI, and establishes appropriate safeguards and steps that must be taken in the event of a breach or disallowed disclosure of PHI. Best practice requires that providers establish robust protocols, policies, and processes for handling sensitive information.

During the COVID-19 pandemic, however, certain HIPAA restrictions relating to telemedicine have been temporarily waived by the US Department of Health and Human Services (HHS). More specifically, HHS Secretary Alex Azar has exercised his authority to waive sanctions against covered hospitals for noncompliance with requirements: to obtain a patient’s consent to speak with family members or friends involved in the patient’s care, to distribute a notice of privacy practices, to request privacy restrictions, to request confidential communications, and the use of nonpublic facing audio and video communications products, among others.⁵ These are temporary measures only; once the national public health emergency has passed or at the HHS Secretary’s discretion based on new developments, this position on discretionary nonenforcement may end.

Continue to: Crisis creates opportunity: The future of telemedicine...

Crisis creates opportunity: The future of telemedicine

It was just a few years ago when the use of telemedicine was relegated to treating patients in only rural areas or those located a great distance from brick and mortar practices. But the pandemic, along with the coincident relaxation of the Centers for Medicare and Medicaid Services’ (CMS) requirements for conducting telemedicine visits has made the technology highly attractive to ObGyns who can now treat many patients 24/7 from their homes using laptops and even mobile devices. In addition, the pandemic has prompted an expansion of current procedural terminology (CPT) codes that makes it possible to bill patients for telemedicine services and be appropriately compensated.

Thus, as awful as COVID-19 is, we can conclude that it has provided us with opportunities. We predict that when the crisis has abated, although the current relaxation of HIPAA guidelines will probably be rescinded, restrictions will not likely return to precoronavirus status; changes will certainly be made, and telemedicine will likely become part and parcel of caring for ObGyn patients.

Telemedicine has been used successfully for years to improve patient access to medical care while reducing health care costs. In 2016, an estimated 61% of US health care institutions and 40% to 50% of US hospitals used telemedicine.⁶ And according to the results of a survey of America’s physicians conducted in April 2020, almost half (48%) are treating patients through telemedicine, which is up from just 18% 2 years ago.⁷

Letting loose the genie in the bottle

Widespread use of telemedicine traditionally has been limited by low reimbursement rates and interstate licensing and practice issues, but we predict that the use of telemedicine is going to significantly increase in the future. Here’s why:⁸ Disruptive innovation was defined by Professor Clayton Christensen of the Harvard Business School in 1997.⁹ Disruptive innovation explains the process by which a disruptive force spurs the development of simple, convenient, and affordable solutions that then replace processes that are expensive and complicated. According to Christensen, a critical element of the process is a technology that makes a product or service more accessible to a larger number of people while reducing cost and increasing ease of use. For example, innovations making equipment for dialysis cheaper and simpler helped make it possible to administer the treatment in neighborhood clinics, rather than in centralized hospitals, thus disrupting the hospital’s share of the dialysis business.

The concept of telemedicine and the technology for its implementation have been available for more than 15 years. However, it was the coronavirus that released the genie from the bottle, serving as the disruptive force to release the innovation. Telemedicine has demonstrated that the technology offers solutions that address patients’ urgent, unmet needs for access to care at an affordable price and that enhances the productivity of the ObGyn. The result is simple, convenient, and affordable; patients can readily access the medical care they need to effectively maintain their health or manage conditions that arise.

Telemedicine has reached a level of critical mass. Data suggest that patients, especially younger ones, have accepted and appreciate the use of this technology.¹⁰ It gives patients more opportunities to receive health care in their homes or at work where they feel more comfortable and less anxious than they do in physicians’ offices.

Several other health care issues may be altered by telemedicine.

The physician shortage. If the data are to be believed, there will be a significant shortage of physicians—and perhaps ObGyns—in the near future.¹¹ Telemedicine can help the problem by making it possible to provide medical care not only in rural areas where there are no ObGyns but also in urban areas where a shortage may be looming.

Continuing medical education (CME). CME is moving from large, expensive, in-person conferences to virtual conferences and online learning.

The American health care budget is bloated with expenses exceeding $3 trillion.¹² Telemedicine can help reduce health care costs by facilitating patient appointments that do not require office staff or many of the overhead expenses associated with brick and mortar operations. Telemedicine reduces the financial impact of patient no-shows. Because patients are keen on participating, the use of telemedicine likely will improve patient engagement and clinical outcomes. Telemedicine already has a reputation of reducing unnecessary office and emergency room visits and hospital admissions.¹³

Clinical trials. One of the obstacles to overcome in the early stages of a clinical trial is finding participants. Telemedicine will make patient recruitment more straightforward. And because telemedicine makes distance from the office a nonissue, recruiters will be less restricted by geographic boundaries.

In addition, telemedicine allows for the participants of the trial to stay in their homes most of the time while wearing remote monitoring devices. Such devices would enable trial researchers to spot deviations from patients’ baseline readings.

The bottom line

COVID-19 has provided the opportunity for us to see how telemedicine can contribute to reducing the spread of infectious diseases by protecting physicians, their staff, and patients themselves. Once the COVID-19 crisis has passed, it is likely that telemedicine will continue to move health care delivery from the hospital or clinic into the home. The growth and integration of information and communication technologies into health care delivery holds great potential for patients, providers, and payers in health systems of the future. ●

In the first 2 articles of this series, “Telemedicine: A primer for today’s ObGyn” and “Telemedicine: Common hurdles and proper coding for ObGyns,” which appeared in the May and June issues of OBG Management, we discussed caring for patients without face-to-face visits and that virtual visits are an opportunity to provide good care in a world such as that created by COVID-19. We also discussed which patients are the most appropriate candidates for telemedicine, as well as how to properly code virtual visits so that you are paid for your time and service. This third article addresses the legal concerns and caveats of using telemedicine and makes a prediction for the future of virtual health care.

Legal issues surrounding telemedicine

There are numerous legal, regulatory, and compliance issues that existed before the pandemic that likely will continue to be of concern postpandemic. Although the recent 1135 waiver (allowing Medicare to pay for office, hospital, and other visits furnished via telehealth)¹ and other regulations are now in place for almost every aspect of telemedicine, virtual medicine is not a free-for-all (even though it may seem like it). Practicing ethical telemedicine entails abiding by numerous federal and state-specific laws and requirements. It is important to be aware of the laws in each state in which your patients are located and to practice according to the requirements of these laws. This often requires consultation with an experienced health care attorney who is knowledgeable about the use of telemedicine and who can help you with issues surrounding:

• Malpractice insurance. It is an important first step to contact your practice’s malpractice insurance carrier and confirm coverage for telemedicine visits. Telemedicine visits are considered the same as in-person visits when determining scope of practice and malpractice liability. Nevertheless, a best practice is to have written verification from your malpractice carrier about the types of telemedicine services and claims for which your ObGyn practice is covered. Additionally, if you care for patients virtually who live in a state in which you are not licensed, check with your carrier to determine if potential claims will be covered.
• Corporate practice laws. These laws require that your practice be governed by a health care professional and not someone with a nonmedical background. This becomes important if you are looking to create a virtual practice in another state. States that prohibit the corporate practice of medicine have state-specific mandates that require strict adherence. Consult with a health care attorney before entering into a business arrangement with a nonphysician or corporate entity.
• Delegation agreement requirements. These laws require physician collaboration and/or supervision of allied health care workers such as nurse practitioners (NPs) and physician assistants (PAs) and may limit the number of allied health care providers that a physician may supervise. Many states are allowing allied health care workers to practice at the top of their license, but this is still state specific. Thus, it is an important issue to consider, especially for practices that rely heavily on the services of advanced practice registered nurses (APRNs), for example, who have a broad scope of practice and who may be qualified to care for many common ObGyn problems.
• Informed consent requirements. Some states have no requirements regarding consent for a virtual visit. Others require either written or verbal consent. In states that do not require informed consent, it is best practice to nevertheless obtain either written or oral consent and to document in the patient’s record that consent was obtained before initiating a virtual visit. The consent should follow state-mandated disclosures, as well as the practice’s policies regarding billing, scheduling, and cancellations of telemedicine visits.
• Interstate licensing laws. Because of the COVID-19 pandemic, federal and state licensure waivers are in place to allow physicians to care for patients outside the physician’s home state, but these waivers likely will be lifted postpandemic. Once waivers are lifted, physicians will need to be licensed not only in the state in which they practice but also in the state where the patient is located at the time of treatment. Even physicians who practice in states that belong to the Interstate Medical Licensure Compact² must apply for and obtain a license to practice within Compact member states. Membership in the Interstate Medical Licensure Compact expedites the licensure process, but does not alleviate the need to obtain a license to practice in each member state. To ensure compliance with interstate licensure laws, seek advice from a health care attorney specializing in telemedicine.
• Drug monitoring laws. The Ryan Haight Online Pharmacy Consumer Protection Act of 2008³ implemented a requirement that physicians have at least one in-person, face-to-face visit with patients before prescribing a controlled substance for the first time. Because state laws may vary, we suggest consulting with a health care attorney to understand your state’s requirements for prescribing controlled substances to new patients and when using telemedicine (see “Prescription drugs” at https://www.cdc.gov/phlp/publications/topic/prescription.html for more information).
• Data privacy and security. From a content perspective, health care data and personally identifiable information are extremely rich, which makes electronic health records (EHRs), or the digital form of patients’ medical histories and other data, particularly tempting targets for hackers and cyber criminals. We caution that services such as Facetime and Skype are not encrypted; they have been granted waivers for telemedicine use, but these waivers are probably not going to be permanent once the COVID-19 crisis passes.
• HIPAA compliance. Generally—and certainly under normal circumstances—telemedicine is subject to the same rules governing protected health information (PHI) as any other technology and process used in physician practices. The Health Insurance Portability and Accountability Act (HIPAA) Security Rule includes guidelines on telemedicine and stipulates that only authorized users should have access to ePHI, that a system of secure communication must be established to protect the security of ePHI, and that a system to monitor communications must be maintained, among other requirements.⁴ Third parties that provide telemedicine, data storage, and other services, with a few exceptions, must have a business associate agreement (BAA) with a covered entity. Covered entities include health care providers, health plans, and health and health care clearinghouses. Such an agreement should include specific language that ensures that HIPAA requirements will be met and that governs permitted and required uses of PHI, strictly limits other uses of PHI, and establishes appropriate safeguards and steps that must be taken in the event of a breach or disallowed disclosure of PHI. Best practice requires that providers establish robust protocols, policies, and processes for handling sensitive information.

During the COVID-19 pandemic, however, certain HIPAA restrictions relating to telemedicine have been temporarily waived by the US Department of Health and Human Services (HHS). More specifically, HHS Secretary Alex Azar has exercised his authority to waive sanctions against covered hospitals for noncompliance with requirements: to obtain a patient’s consent to speak with family members or friends involved in the patient’s care, to distribute a notice of privacy practices, to request privacy restrictions, to request confidential communications, and the use of nonpublic facing audio and video communications products, among others.⁵ These are temporary measures only; once the national public health emergency has passed or at the HHS Secretary’s discretion based on new developments, this position on discretionary nonenforcement may end.

Continue to: Crisis creates opportunity: The future of telemedicine...

Crisis creates opportunity: The future of telemedicine

It was just a few years ago when the use of telemedicine was relegated to treating patients in only rural areas or those located a great distance from brick and mortar practices. But the pandemic, along with the coincident relaxation of the Centers for Medicare and Medicaid Services’ (CMS) requirements for conducting telemedicine visits has made the technology highly attractive to ObGyns who can now treat many patients 24/7 from their homes using laptops and even mobile devices. In addition, the pandemic has prompted an expansion of current procedural terminology (CPT) codes that makes it possible to bill patients for telemedicine services and be appropriately compensated.

Thus, as awful as COVID-19 is, we can conclude that it has provided us with opportunities. We predict that when the crisis has abated, although the current relaxation of HIPAA guidelines will probably be rescinded, restrictions will not likely return to precoronavirus status; changes will certainly be made, and telemedicine will likely become part and parcel of caring for ObGyn patients.

Telemedicine has been used successfully for years to improve patient access to medical care while reducing health care costs. In 2016, an estimated 61% of US health care institutions and 40% to 50% of US hospitals used telemedicine.⁶ And according to the results of a survey of America’s physicians conducted in April 2020, almost half (48%) are treating patients through telemedicine, which is up from just 18% 2 years ago.⁷

Letting loose the genie in the bottle

Widespread use of telemedicine traditionally has been limited by low reimbursement rates and interstate licensing and practice issues, but we predict that the use of telemedicine is going to significantly increase in the future. Here’s why:⁸ Disruptive innovation was defined by Professor Clayton Christensen of the Harvard Business School in 1997.⁹ Disruptive innovation explains the process by which a disruptive force spurs the development of simple, convenient, and affordable solutions that then replace processes that are expensive and complicated. According to Christensen, a critical element of the process is a technology that makes a product or service more accessible to a larger number of people while reducing cost and increasing ease of use. For example, innovations making equipment for dialysis cheaper and simpler helped make it possible to administer the treatment in neighborhood clinics, rather than in centralized hospitals, thus disrupting the hospital’s share of the dialysis business.

The concept of telemedicine and the technology for its implementation have been available for more than 15 years. However, it was the coronavirus that released the genie from the bottle, serving as the disruptive force to release the innovation. Telemedicine has demonstrated that the technology offers solutions that address patients’ urgent, unmet needs for access to care at an affordable price and that enhances the productivity of the ObGyn. The result is simple, convenient, and affordable; patients can readily access the medical care they need to effectively maintain their health or manage conditions that arise.

Telemedicine has reached a level of critical mass. Data suggest that patients, especially younger ones, have accepted and appreciate the use of this technology.¹⁰ It gives patients more opportunities to receive health care in their homes or at work where they feel more comfortable and less anxious than they do in physicians’ offices.

Several other health care issues may be altered by telemedicine.

The physician shortage. If the data are to be believed, there will be a significant shortage of physicians—and perhaps ObGyns—in the near future.¹¹ Telemedicine can help the problem by making it possible to provide medical care not only in rural areas where there are no ObGyns but also in urban areas where a shortage may be looming.

Continuing medical education (CME). CME is moving from large, expensive, in-person conferences to virtual conferences and online learning.

The American health care budget is bloated with expenses exceeding $3 trillion.¹² Telemedicine can help reduce health care costs by facilitating patient appointments that do not require office staff or many of the overhead expenses associated with brick and mortar operations. Telemedicine reduces the financial impact of patient no-shows. Because patients are keen on participating, the use of telemedicine likely will improve patient engagement and clinical outcomes. Telemedicine already has a reputation of reducing unnecessary office and emergency room visits and hospital admissions.¹³

Clinical trials. One of the obstacles to overcome in the early stages of a clinical trial is finding participants. Telemedicine will make patient recruitment more straightforward. And because telemedicine makes distance from the office a nonissue, recruiters will be less restricted by geographic boundaries.

In addition, telemedicine allows for the participants of the trial to stay in their homes most of the time while wearing remote monitoring devices. Such devices would enable trial researchers to spot deviations from patients’ baseline readings.

The bottom line

COVID-19 has provided the opportunity for us to see how telemedicine can contribute to reducing the spread of infectious diseases by protecting physicians, their staff, and patients themselves. Once the COVID-19 crisis has passed, it is likely that telemedicine will continue to move health care delivery from the hospital or clinic into the home. The growth and integration of information and communication technologies into health care delivery holds great potential for patients, providers, and payers in health systems of the future. ●

The COVID-19 pandemic has created a metamorphosis in human interactions. One way we have adapted is our increased use of virtual platforms for tasks such as lectures, meetings, interviews, conferences, and patient care via telemedicine.¹ Virtual platforms have allowed for the continuation of existing programs and facilitated new collaborations ranging from international webinars on patient care to national lectures for residents and fellows in ObGyn. New virtual platforms continue to emerge. We present here a review of free virtual communication apps available to the ObGyn care provider.

We used the term “videoconference” to search the Apple and Google Play app stores between May 29, 2020, and June 1, 2020. A total of 25 apps that offered both audio and videoconferencing were identified. All were free for download, but the majority required an ongoing paid subscription fee for the service. Thirteen programs were either completely free or offered a free version of their services. Based on our review and a systematic analysis, we selected 5 apps to feature here: Cisco Webex Meetings, Free Conference Call, Jitsi Meet, Microsoft Teams, and Zoom.

Featured videoconferencing apps

Cisco Webex Meetings and Free Conference Call offer an easy video meeting setup from both a smartphone and a desktop app. They provide seamless access to functions on the virtual main page, including chat with other participants in the meeting and screen sharing. These apps both require screen recording in order to share screens.

Jitsi Meet is a web app usable on an iPhone or Android as well as on a desktop through the meet.jit.si website. No account is required. On the app or website, the user creates a meeting name and shares the unique URL or meeting name with invitees to join the videoconference. The mobile app and website both offer a “raise your hand” feature, full screen and/or gallery (tile) view, group chat, and live streaming. In both settings, users may lock the meeting and require a password. Additional features through the website include screen sharing, recording the meeting, blurred background, muting all participants, and sharing YouTube videos.

The Microsoft Teams app asks you the purpose of signing up on the website—“use for school,” “with friends and family,” or “for work.” If you choose “with friends and family,” the app directs you to Skype. Choosing the “for work” function directs you to complete your free registration. Microsoft Teams requires participants to create teams; thus, others participating in the videoconference need to have their own account. However, “guest access” also is available.

On the Zoom platform, immediate and scheduled meetings can be set up on the app as well as on the website, or directly on Microsoft Outlook and Google Calendar if the plug-in has been established. The desktop and smartphone apps are similar in function and provide access to personalized settings.

For patient care, since HIPAA (Health Insurance Portability and Accountability Act) protection is a concern, we recommend following guidelines at the user’s institution regarding use of apps such as Epic Haiku for telehealth visits. For teaching and interacting with colleagues, we recommend Cisco Webex, Free Conference Call, Microsoft Teams, and Zoom, keeping in mind the time limitations of each app for the free account.

Overall, these 5 apps are easy to set up and user-friendly. Deciding which program to choose will depend on the number of participants allowed for a meeting and the duration of the meeting, as these two factors seem to be the most constraining among the free videoconferencing apps. ●

The COVID-19 pandemic has created a metamorphosis in human interactions. One way we have adapted is our increased use of virtual platforms for tasks such as lectures, meetings, interviews, conferences, and patient care via telemedicine.¹ Virtual platforms have allowed for the continuation of existing programs and facilitated new collaborations ranging from international webinars on patient care to national lectures for residents and fellows in ObGyn. New virtual platforms continue to emerge. We present here a review of free virtual communication apps available to the ObGyn care provider.

We used the term “videoconference” to search the Apple and Google Play app stores between May 29, 2020, and June 1, 2020. A total of 25 apps that offered both audio and videoconferencing were identified. All were free for download, but the majority required an ongoing paid subscription fee for the service. Thirteen programs were either completely free or offered a free version of their services. Based on our review and a systematic analysis, we selected 5 apps to feature here: Cisco Webex Meetings, Free Conference Call, Jitsi Meet, Microsoft Teams, and Zoom.

Featured videoconferencing apps

Cisco Webex Meetings and Free Conference Call offer an easy video meeting setup from both a smartphone and a desktop app. They provide seamless access to functions on the virtual main page, including chat with other participants in the meeting and screen sharing. These apps both require screen recording in order to share screens.

Jitsi Meet is a web app usable on an iPhone or Android as well as on a desktop through the meet.jit.si website. No account is required. On the app or website, the user creates a meeting name and shares the unique URL or meeting name with invitees to join the videoconference. The mobile app and website both offer a “raise your hand” feature, full screen and/or gallery (tile) view, group chat, and live streaming. In both settings, users may lock the meeting and require a password. Additional features through the website include screen sharing, recording the meeting, blurred background, muting all participants, and sharing YouTube videos.

The Microsoft Teams app asks you the purpose of signing up on the website—“use for school,” “with friends and family,” or “for work.” If you choose “with friends and family,” the app directs you to Skype. Choosing the “for work” function directs you to complete your free registration. Microsoft Teams requires participants to create teams; thus, others participating in the videoconference need to have their own account. However, “guest access” also is available.

On the Zoom platform, immediate and scheduled meetings can be set up on the app as well as on the website, or directly on Microsoft Outlook and Google Calendar if the plug-in has been established. The desktop and smartphone apps are similar in function and provide access to personalized settings.

For patient care, since HIPAA (Health Insurance Portability and Accountability Act) protection is a concern, we recommend following guidelines at the user’s institution regarding use of apps such as Epic Haiku for telehealth visits. For teaching and interacting with colleagues, we recommend Cisco Webex, Free Conference Call, Microsoft Teams, and Zoom, keeping in mind the time limitations of each app for the free account.

Overall, these 5 apps are easy to set up and user-friendly. Deciding which program to choose will depend on the number of participants allowed for a meeting and the duration of the meeting, as these two factors seem to be the most constraining among the free videoconferencing apps. ●

The COVID-19 pandemic has created a metamorphosis in human interactions. One way we have adapted is our increased use of virtual platforms for tasks such as lectures, meetings, interviews, conferences, and patient care via telemedicine.¹ Virtual platforms have allowed for the continuation of existing programs and facilitated new collaborations ranging from international webinars on patient care to national lectures for residents and fellows in ObGyn. New virtual platforms continue to emerge. We present here a review of free virtual communication apps available to the ObGyn care provider.

We used the term “videoconference” to search the Apple and Google Play app stores between May 29, 2020, and June 1, 2020. A total of 25 apps that offered both audio and videoconferencing were identified. All were free for download, but the majority required an ongoing paid subscription fee for the service. Thirteen programs were either completely free or offered a free version of their services. Based on our review and a systematic analysis, we selected 5 apps to feature here: Cisco Webex Meetings, Free Conference Call, Jitsi Meet, Microsoft Teams, and Zoom.

Featured videoconferencing apps

Cisco Webex Meetings and Free Conference Call offer an easy video meeting setup from both a smartphone and a desktop app. They provide seamless access to functions on the virtual main page, including chat with other participants in the meeting and screen sharing. These apps both require screen recording in order to share screens.

Jitsi Meet is a web app usable on an iPhone or Android as well as on a desktop through the meet.jit.si website. No account is required. On the app or website, the user creates a meeting name and shares the unique URL or meeting name with invitees to join the videoconference. The mobile app and website both offer a “raise your hand” feature, full screen and/or gallery (tile) view, group chat, and live streaming. In both settings, users may lock the meeting and require a password. Additional features through the website include screen sharing, recording the meeting, blurred background, muting all participants, and sharing YouTube videos.

The Microsoft Teams app asks you the purpose of signing up on the website—“use for school,” “with friends and family,” or “for work.” If you choose “with friends and family,” the app directs you to Skype. Choosing the “for work” function directs you to complete your free registration. Microsoft Teams requires participants to create teams; thus, others participating in the videoconference need to have their own account. However, “guest access” also is available.

On the Zoom platform, immediate and scheduled meetings can be set up on the app as well as on the website, or directly on Microsoft Outlook and Google Calendar if the plug-in has been established. The desktop and smartphone apps are similar in function and provide access to personalized settings.

For patient care, since HIPAA (Health Insurance Portability and Accountability Act) protection is a concern, we recommend following guidelines at the user’s institution regarding use of apps such as Epic Haiku for telehealth visits. For teaching and interacting with colleagues, we recommend Cisco Webex, Free Conference Call, Microsoft Teams, and Zoom, keeping in mind the time limitations of each app for the free account.

Overall, these 5 apps are easy to set up and user-friendly. Deciding which program to choose will depend on the number of participants allowed for a meeting and the duration of the meeting, as these two factors seem to be the most constraining among the free videoconferencing apps. ●

Clinicians shouldn’t rely on pulmonary function tests (PFTs) alone to screen for interstitial lung disease (ILD). The tests performed poorly in a retrospective study of 212 patients with systemic sclerosis, reinforcing the findings of previous studies.

Any screening algorithm should include high-resolution CT (HRCT), which is good at prognosticating disease, the investigators wrote in Arthritis & Rheumatology. “I think all newly diagnosed systemic sclerosis patients should have a full set of PFTs (spirometry, lung volumes, and diffusion capacity) and an HRCT at baseline to evaluate for ILD,” the study’s lead author, Elana J. Bernstein, MD, said in an interview.

ILD is a leading cause of death in systemic sclerosis (SSc) patients, affecting 40%-60% of those with the disease. HRCT is currently the preferred option for detection of ILD. PFTs are commonly used to screen for ILD but haven’t performed well in previous studies. “Someone can have abnormalities on HRCT that are consistent with ILD but still have PFTs that are in the ‘normal’ range,” explained Dr. Bernstein of Columbia University, New York. One cross-sectional study of 102 SSc patients found that the test’s sensitivity for the detection of ILD on HRCT was just 37.5% when forced vital capacity (FVC) <80% predicted.

Investigators sought to assess performance characteristics of PFTs in patients with early diffuse cutaneous SSc, a cohort at high risk of developing ILD. The study enlisted patients from the Prospective Registry of Early Systemic Sclerosis (PRESS), a multicenter, prospective cohort study of adults with early diffuse cutaneous SSc. Overall, 212 patients at 11 U.S. academic medical centers participated in the study from April 2012 to January 2019.

All patients had spirometry (PFT) and HRCT chest scans. PFTs were conducted per American Thoracic Society/European Respiratory Society guidelines. The investigators calculated test characteristics for single PFT and combinations of PFT parameters for the detection of ILD on HRCT. The HRCTs were ordered at the discretion of treating physicians, and scrutinized for ILD features such as reticular changes, honeycombing, traction bronchiectasis, and ground-glass opacities. The investigators defined the lower limit of normal for FVC, total lung capacity, and diffusion capacity for carbon monoxide (DLCO) as 80% predicted.

Overall, Dr. Bernstein and her colleagues found that PFTs lacked sufficient sensitivity and negative predictive value for the detection of ILD on HRCT in these patients.

An FVC <80% predicted performed at only 63% sensitivity and an false negative rate of 37%. Total lung capacity or DLCO <80% predicted had a sensitivity of 46% and 80%, respectively. The combination of FVC or DLCO <80% predicted raised sensitivity to 85%. However, the addition of total lung capacity to this combination did not improve results.

Overall, PFTs had a positive predictive value of 64%-74% and an negative predictive value of 61%-70%. “This means that PFT alone will not accurately predict the presence of ILD in about 35%, and not be correctly negative in about 35%,” observed Daniel E. Furst, MD, professor of medicine (emeritus) at the University of California, Los Angeles, and professor of rheumatology at the University of California, Los Angeles.

While the combination of FVC <80% predicted or DLCO <80% predicted performed better than the other parameters, the sensitivity “is inadequate for an ILD screening test as it results in an false negative rate of 15%, thereby falsely reassuring 15% of patients that they do not have ILD when in fact they do,” the investigators observed.

“This study reinforces the notion that PFTs alone are ineffective screening tools for ILD in the presence of systemic sclerosis, particularly for patients with early systemic sclerosis,” said Elizabeth Volkmann, MD, MS, assistant professor and codirector of the CTD-ILD program in the division of rheumatology at the University of California, Los Angeles.

The study’s scope was relatively small, yet the results provide further evidence to show that HRCT should be performed in all SSc patients to screen for the presence of ILD, Dr. Volkmann said in an interview.

Other research has demonstrated the value of baseline HRCT as a prognosticator of ILD outcomes. The method provides useful information about the degree of fibrosis and degree of damage in early-stage disease, said Dr. Furst, also an adjunct professor at the University of Washington, Seattle, and a research professor at the University of Florence (Italy). “If there’s honeycombing, that’s a bad prognosis. If it’s ground glass or reticular changes, the prognosis is better.

“Once there’s a lot of damage, it’s much harder to interpret disease with HRCT,” he added.

HRCT and PFT work well together to assess what’s happening in patients, Dr. Furst explained. HRCT provides an idea of anatomic changes, whereas PFT outlines aspects of functional change to diagnose early ILD in early diffuse SSc. The study results should not apply to patients with later disease who have more developed ILD, he noted.

The investigators acknowledged that they weren’t able to categorize and analyze patients according to disease extent because they didn’t quantify the extent of ILD. Another limitation was that the HRCTs and PFTs were ordered at the discretion of individual physicians, which means that not all participants received the tests.

“Although the tests were done in 90% of the population, there is still a probability of a significant selection bias,” Dr. Furst said.

Dr. Bernstein and several other coauthors in the study received grants from the National Institute of Arthritis and Musculoskeletal and Skin Diseases to support their work. Dr. Furst disclosed receiving grant/research support from and/or consulting for AbbVie, Actelion, Amgen, Bristol-Myers Squibb, Corbus, the National Institutes of Health, Novartis, Pfizer, and Roche/Genentech. Dr. Volkmann disclosed consulting for and/or receiving grant support from Boehringer Ingelheim, Corbus, and Forbius.

SOURCE: Bernstein EJ et al. Arthritis Rheumatol. 2020 Jun 25. doi: 10.1002/art.41415.

Clinicians shouldn’t rely on pulmonary function tests (PFTs) alone to screen for interstitial lung disease (ILD). The tests performed poorly in a retrospective study of 212 patients with systemic sclerosis, reinforcing the findings of previous studies.

Any screening algorithm should include high-resolution CT (HRCT), which is good at prognosticating disease, the investigators wrote in Arthritis & Rheumatology. “I think all newly diagnosed systemic sclerosis patients should have a full set of PFTs (spirometry, lung volumes, and diffusion capacity) and an HRCT at baseline to evaluate for ILD,” the study’s lead author, Elana J. Bernstein, MD, said in an interview.

ILD is a leading cause of death in systemic sclerosis (SSc) patients, affecting 40%-60% of those with the disease. HRCT is currently the preferred option for detection of ILD. PFTs are commonly used to screen for ILD but haven’t performed well in previous studies. “Someone can have abnormalities on HRCT that are consistent with ILD but still have PFTs that are in the ‘normal’ range,” explained Dr. Bernstein of Columbia University, New York. One cross-sectional study of 102 SSc patients found that the test’s sensitivity for the detection of ILD on HRCT was just 37.5% when forced vital capacity (FVC) <80% predicted.

Investigators sought to assess performance characteristics of PFTs in patients with early diffuse cutaneous SSc, a cohort at high risk of developing ILD. The study enlisted patients from the Prospective Registry of Early Systemic Sclerosis (PRESS), a multicenter, prospective cohort study of adults with early diffuse cutaneous SSc. Overall, 212 patients at 11 U.S. academic medical centers participated in the study from April 2012 to January 2019.

All patients had spirometry (PFT) and HRCT chest scans. PFTs were conducted per American Thoracic Society/European Respiratory Society guidelines. The investigators calculated test characteristics for single PFT and combinations of PFT parameters for the detection of ILD on HRCT. The HRCTs were ordered at the discretion of treating physicians, and scrutinized for ILD features such as reticular changes, honeycombing, traction bronchiectasis, and ground-glass opacities. The investigators defined the lower limit of normal for FVC, total lung capacity, and diffusion capacity for carbon monoxide (DLCO) as 80% predicted.

Overall, Dr. Bernstein and her colleagues found that PFTs lacked sufficient sensitivity and negative predictive value for the detection of ILD on HRCT in these patients.

An FVC <80% predicted performed at only 63% sensitivity and an false negative rate of 37%. Total lung capacity or DLCO <80% predicted had a sensitivity of 46% and 80%, respectively. The combination of FVC or DLCO <80% predicted raised sensitivity to 85%. However, the addition of total lung capacity to this combination did not improve results.

Overall, PFTs had a positive predictive value of 64%-74% and an negative predictive value of 61%-70%. “This means that PFT alone will not accurately predict the presence of ILD in about 35%, and not be correctly negative in about 35%,” observed Daniel E. Furst, MD, professor of medicine (emeritus) at the University of California, Los Angeles, and professor of rheumatology at the University of California, Los Angeles.

While the combination of FVC <80% predicted or DLCO <80% predicted performed better than the other parameters, the sensitivity “is inadequate for an ILD screening test as it results in an false negative rate of 15%, thereby falsely reassuring 15% of patients that they do not have ILD when in fact they do,” the investigators observed.

“This study reinforces the notion that PFTs alone are ineffective screening tools for ILD in the presence of systemic sclerosis, particularly for patients with early systemic sclerosis,” said Elizabeth Volkmann, MD, MS, assistant professor and codirector of the CTD-ILD program in the division of rheumatology at the University of California, Los Angeles.

The study’s scope was relatively small, yet the results provide further evidence to show that HRCT should be performed in all SSc patients to screen for the presence of ILD, Dr. Volkmann said in an interview.

Other research has demonstrated the value of baseline HRCT as a prognosticator of ILD outcomes. The method provides useful information about the degree of fibrosis and degree of damage in early-stage disease, said Dr. Furst, also an adjunct professor at the University of Washington, Seattle, and a research professor at the University of Florence (Italy). “If there’s honeycombing, that’s a bad prognosis. If it’s ground glass or reticular changes, the prognosis is better.

“Once there’s a lot of damage, it’s much harder to interpret disease with HRCT,” he added.

HRCT and PFT work well together to assess what’s happening in patients, Dr. Furst explained. HRCT provides an idea of anatomic changes, whereas PFT outlines aspects of functional change to diagnose early ILD in early diffuse SSc. The study results should not apply to patients with later disease who have more developed ILD, he noted.

The investigators acknowledged that they weren’t able to categorize and analyze patients according to disease extent because they didn’t quantify the extent of ILD. Another limitation was that the HRCTs and PFTs were ordered at the discretion of individual physicians, which means that not all participants received the tests.

“Although the tests were done in 90% of the population, there is still a probability of a significant selection bias,” Dr. Furst said.

Dr. Bernstein and several other coauthors in the study received grants from the National Institute of Arthritis and Musculoskeletal and Skin Diseases to support their work. Dr. Furst disclosed receiving grant/research support from and/or consulting for AbbVie, Actelion, Amgen, Bristol-Myers Squibb, Corbus, the National Institutes of Health, Novartis, Pfizer, and Roche/Genentech. Dr. Volkmann disclosed consulting for and/or receiving grant support from Boehringer Ingelheim, Corbus, and Forbius.

SOURCE: Bernstein EJ et al. Arthritis Rheumatol. 2020 Jun 25. doi: 10.1002/art.41415.

Clinicians shouldn’t rely on pulmonary function tests (PFTs) alone to screen for interstitial lung disease (ILD). The tests performed poorly in a retrospective study of 212 patients with systemic sclerosis, reinforcing the findings of previous studies.

Any screening algorithm should include high-resolution CT (HRCT), which is good at prognosticating disease, the investigators wrote in Arthritis & Rheumatology. “I think all newly diagnosed systemic sclerosis patients should have a full set of PFTs (spirometry, lung volumes, and diffusion capacity) and an HRCT at baseline to evaluate for ILD,” the study’s lead author, Elana J. Bernstein, MD, said in an interview.

ILD is a leading cause of death in systemic sclerosis (SSc) patients, affecting 40%-60% of those with the disease. HRCT is currently the preferred option for detection of ILD. PFTs are commonly used to screen for ILD but haven’t performed well in previous studies. “Someone can have abnormalities on HRCT that are consistent with ILD but still have PFTs that are in the ‘normal’ range,” explained Dr. Bernstein of Columbia University, New York. One cross-sectional study of 102 SSc patients found that the test’s sensitivity for the detection of ILD on HRCT was just 37.5% when forced vital capacity (FVC) <80% predicted.

Investigators sought to assess performance characteristics of PFTs in patients with early diffuse cutaneous SSc, a cohort at high risk of developing ILD. The study enlisted patients from the Prospective Registry of Early Systemic Sclerosis (PRESS), a multicenter, prospective cohort study of adults with early diffuse cutaneous SSc. Overall, 212 patients at 11 U.S. academic medical centers participated in the study from April 2012 to January 2019.

All patients had spirometry (PFT) and HRCT chest scans. PFTs were conducted per American Thoracic Society/European Respiratory Society guidelines. The investigators calculated test characteristics for single PFT and combinations of PFT parameters for the detection of ILD on HRCT. The HRCTs were ordered at the discretion of treating physicians, and scrutinized for ILD features such as reticular changes, honeycombing, traction bronchiectasis, and ground-glass opacities. The investigators defined the lower limit of normal for FVC, total lung capacity, and diffusion capacity for carbon monoxide (DLCO) as 80% predicted.

Overall, Dr. Bernstein and her colleagues found that PFTs lacked sufficient sensitivity and negative predictive value for the detection of ILD on HRCT in these patients.

An FVC <80% predicted performed at only 63% sensitivity and an false negative rate of 37%. Total lung capacity or DLCO <80% predicted had a sensitivity of 46% and 80%, respectively. The combination of FVC or DLCO <80% predicted raised sensitivity to 85%. However, the addition of total lung capacity to this combination did not improve results.

Overall, PFTs had a positive predictive value of 64%-74% and an negative predictive value of 61%-70%. “This means that PFT alone will not accurately predict the presence of ILD in about 35%, and not be correctly negative in about 35%,” observed Daniel E. Furst, MD, professor of medicine (emeritus) at the University of California, Los Angeles, and professor of rheumatology at the University of California, Los Angeles.

While the combination of FVC <80% predicted or DLCO <80% predicted performed better than the other parameters, the sensitivity “is inadequate for an ILD screening test as it results in an false negative rate of 15%, thereby falsely reassuring 15% of patients that they do not have ILD when in fact they do,” the investigators observed.

“This study reinforces the notion that PFTs alone are ineffective screening tools for ILD in the presence of systemic sclerosis, particularly for patients with early systemic sclerosis,” said Elizabeth Volkmann, MD, MS, assistant professor and codirector of the CTD-ILD program in the division of rheumatology at the University of California, Los Angeles.

The study’s scope was relatively small, yet the results provide further evidence to show that HRCT should be performed in all SSc patients to screen for the presence of ILD, Dr. Volkmann said in an interview.

Other research has demonstrated the value of baseline HRCT as a prognosticator of ILD outcomes. The method provides useful information about the degree of fibrosis and degree of damage in early-stage disease, said Dr. Furst, also an adjunct professor at the University of Washington, Seattle, and a research professor at the University of Florence (Italy). “If there’s honeycombing, that’s a bad prognosis. If it’s ground glass or reticular changes, the prognosis is better.

“Once there’s a lot of damage, it’s much harder to interpret disease with HRCT,” he added.

HRCT and PFT work well together to assess what’s happening in patients, Dr. Furst explained. HRCT provides an idea of anatomic changes, whereas PFT outlines aspects of functional change to diagnose early ILD in early diffuse SSc. The study results should not apply to patients with later disease who have more developed ILD, he noted.

The investigators acknowledged that they weren’t able to categorize and analyze patients according to disease extent because they didn’t quantify the extent of ILD. Another limitation was that the HRCTs and PFTs were ordered at the discretion of individual physicians, which means that not all participants received the tests.

“Although the tests were done in 90% of the population, there is still a probability of a significant selection bias,” Dr. Furst said.

Dr. Bernstein and several other coauthors in the study received grants from the National Institute of Arthritis and Musculoskeletal and Skin Diseases to support their work. Dr. Furst disclosed receiving grant/research support from and/or consulting for AbbVie, Actelion, Amgen, Bristol-Myers Squibb, Corbus, the National Institutes of Health, Novartis, Pfizer, and Roche/Genentech. Dr. Volkmann disclosed consulting for and/or receiving grant support from Boehringer Ingelheim, Corbus, and Forbius.

SOURCE: Bernstein EJ et al. Arthritis Rheumatol. 2020 Jun 25. doi: 10.1002/art.41415.

Lipophilic statin use is associated with reduced mortality risk in women with ovarian cancer, findings from a large observational study suggest.

The study included 10,062 patients with epithelial ovarian cancer enrolled in the Finnish national cancer registry. There were 2,621 patients who were prescribed statins between 1995 and 2015, and 80% of them used lipophilic statins.

When compared with no statin use, any statin use was associated with a 40% reduction in ovarian cancer mortality (weighted hazard ratio, 0.60), and any use of lipophilic statins was associated with a 43% reduction in ovarian cancer mortality (wHR, 0.57).

Kala Visvanathan, MD, of Johns Hopkins University in Baltimore, and colleagues reported these findings in a poster at the AACR virtual meeting II.

Reductions in ovarian cancer mortality were observed in women who took simvastatin or atorvastatin (wHRs 0.24 and 0.20, respectively), the researchers found.

Lipophilic statin use also was associated with a reduction in ovarian cancer mortality across disease subtypes, although the magnitude of reduction varied. The hazard ratios were 0.60 for high-grade serous ovarian cancer, 0.50 for endometrioid ovarian cancer, 0.20 for clear cell ovarian cancer, 0.30 for mucinous ovarian cancer, and 0.27 for borderline disease.

Survival benefits were evident both in patients who started statins prior to their ovarian cancer diagnosis and in those who started statins after diagnosis.

Never-statin users had a median age of 62 years at baseline, and ever-statin users had a median age of 67 years. The median follow-up was 3.6 years and 5.5 years, respectively.

Data from the registry were linked to prescription claims, and a series of analyses were conducted to examine the association between pre- and postdiagnostic statin use and mortality. The findings were adjusted for age at diagnosis, stage, ovarian cancer subtype, treatments, year of diagnosis, and chronic disease medications. Adherence to statins was greater than 90%.
 

Implications and next steps

The idea of using statins for the treatment of ovarian cancer is appealing because of the promising survival data as well as the broad access, low cost, and tolerability of statins, Dr. Visvanathan said in a statement. About 28% of U.S. adults over age 40 routinely take statins for cholesterol control, and statins are widely used in other countries, she said.

“Our results support research to evaluate the repurposing of therapies that are well tolerated and inexpensive in order to help reduce the global cancer burden,” Dr. Visvanathan and colleagues wrote in their poster.

“Our results provide evidence in support of the evaluation of lipophilic statins, particularly atorvastatin and/or simvastatin, for the treatment of [epithelial ovarian cancer] in conjunction with existing therapies,” the researchers wrote. They added that these statins should be “evaluated in randomized clinical trials that include correlative endpoints.”

Further, the researchers argued that “the results are biologically plausible based on known mechanisms associated with statin use and highlight the fact that statins may be effective to treat more than one disease/outcome (i.e., high cholesterol, EOC [epithelial ovarian cancer], breast cancer).”

The results of this study are intriguing, according to James Yarmolinsky, MSc, of the University of Bristol, England. Mr. Yarmolinsky is the lead author of a case-control study that showed an association between genetically proxied 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibition and lower odds of developing epithelial ovarian cancer (JAMA. 2020;323[7]:646-655).

Mr. Yarmolinsky and colleagues found that HMG-CoA reductase inhibition equivalent to a 38.7-mg/dL reduction in low-density lipoprotein cholesterol was significantly associated with lower odds of epithelial ovarian cancer in the general population (odds ratio, 0.60) and among BRCA1/2 mutation carriers (hazard ratio, 0.69). The findings raised questions about whether a similar association would be seen with medications such as statins that inhibit HMG-CoA reductase.

“These findings linking statin use to lower ovarian cancer mortality are really interesting given our own research suggesting that these drugs may also lower women’s risk of developing this disease in the first place,” Mr. Yarmolinsky said.

“The survival rate for ovarian cancer remains the lowest among all gynecological cancers in the United States, so use of these medications in either a preventive or therapeutic context could offer an important approach for reducing disease burden,” he added. “If the findings reported by Visvanathan and colleagues can be shown to replicate in other large population-based studies, testing the efficacy of statins in a randomized clinical trial could provide definitive evidence of whether these medications lower ovarian cancer mortality.”

The Department of Defense and the Breast Cancer Research Foundation funded the current study. Dr. Visvanathan and Mr. Yarmolinsky reported no disclosures.

[email protected]

SOURCE: Visvanathan K et al. AACR 2020, Abstract 5782.

Lipophilic statin use is associated with reduced mortality risk in women with ovarian cancer, findings from a large observational study suggest.

The study included 10,062 patients with epithelial ovarian cancer enrolled in the Finnish national cancer registry. There were 2,621 patients who were prescribed statins between 1995 and 2015, and 80% of them used lipophilic statins.

When compared with no statin use, any statin use was associated with a 40% reduction in ovarian cancer mortality (weighted hazard ratio, 0.60), and any use of lipophilic statins was associated with a 43% reduction in ovarian cancer mortality (wHR, 0.57).

Kala Visvanathan, MD, of Johns Hopkins University in Baltimore, and colleagues reported these findings in a poster at the AACR virtual meeting II.

Reductions in ovarian cancer mortality were observed in women who took simvastatin or atorvastatin (wHRs 0.24 and 0.20, respectively), the researchers found.

Lipophilic statin use also was associated with a reduction in ovarian cancer mortality across disease subtypes, although the magnitude of reduction varied. The hazard ratios were 0.60 for high-grade serous ovarian cancer, 0.50 for endometrioid ovarian cancer, 0.20 for clear cell ovarian cancer, 0.30 for mucinous ovarian cancer, and 0.27 for borderline disease.

Survival benefits were evident both in patients who started statins prior to their ovarian cancer diagnosis and in those who started statins after diagnosis.

Never-statin users had a median age of 62 years at baseline, and ever-statin users had a median age of 67 years. The median follow-up was 3.6 years and 5.5 years, respectively.

Data from the registry were linked to prescription claims, and a series of analyses were conducted to examine the association between pre- and postdiagnostic statin use and mortality. The findings were adjusted for age at diagnosis, stage, ovarian cancer subtype, treatments, year of diagnosis, and chronic disease medications. Adherence to statins was greater than 90%.
 

Implications and next steps

The idea of using statins for the treatment of ovarian cancer is appealing because of the promising survival data as well as the broad access, low cost, and tolerability of statins, Dr. Visvanathan said in a statement. About 28% of U.S. adults over age 40 routinely take statins for cholesterol control, and statins are widely used in other countries, she said.

“Our results support research to evaluate the repurposing of therapies that are well tolerated and inexpensive in order to help reduce the global cancer burden,” Dr. Visvanathan and colleagues wrote in their poster.

“Our results provide evidence in support of the evaluation of lipophilic statins, particularly atorvastatin and/or simvastatin, for the treatment of [epithelial ovarian cancer] in conjunction with existing therapies,” the researchers wrote. They added that these statins should be “evaluated in randomized clinical trials that include correlative endpoints.”

Further, the researchers argued that “the results are biologically plausible based on known mechanisms associated with statin use and highlight the fact that statins may be effective to treat more than one disease/outcome (i.e., high cholesterol, EOC [epithelial ovarian cancer], breast cancer).”

The results of this study are intriguing, according to James Yarmolinsky, MSc, of the University of Bristol, England. Mr. Yarmolinsky is the lead author of a case-control study that showed an association between genetically proxied 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibition and lower odds of developing epithelial ovarian cancer (JAMA. 2020;323[7]:646-655).

Mr. Yarmolinsky and colleagues found that HMG-CoA reductase inhibition equivalent to a 38.7-mg/dL reduction in low-density lipoprotein cholesterol was significantly associated with lower odds of epithelial ovarian cancer in the general population (odds ratio, 0.60) and among BRCA1/2 mutation carriers (hazard ratio, 0.69). The findings raised questions about whether a similar association would be seen with medications such as statins that inhibit HMG-CoA reductase.

“These findings linking statin use to lower ovarian cancer mortality are really interesting given our own research suggesting that these drugs may also lower women’s risk of developing this disease in the first place,” Mr. Yarmolinsky said.

“The survival rate for ovarian cancer remains the lowest among all gynecological cancers in the United States, so use of these medications in either a preventive or therapeutic context could offer an important approach for reducing disease burden,” he added. “If the findings reported by Visvanathan and colleagues can be shown to replicate in other large population-based studies, testing the efficacy of statins in a randomized clinical trial could provide definitive evidence of whether these medications lower ovarian cancer mortality.”

The Department of Defense and the Breast Cancer Research Foundation funded the current study. Dr. Visvanathan and Mr. Yarmolinsky reported no disclosures.

[email protected]

SOURCE: Visvanathan K et al. AACR 2020, Abstract 5782.

Lipophilic statin use is associated with reduced mortality risk in women with ovarian cancer, findings from a large observational study suggest.

The study included 10,062 patients with epithelial ovarian cancer enrolled in the Finnish national cancer registry. There were 2,621 patients who were prescribed statins between 1995 and 2015, and 80% of them used lipophilic statins.

When compared with no statin use, any statin use was associated with a 40% reduction in ovarian cancer mortality (weighted hazard ratio, 0.60), and any use of lipophilic statins was associated with a 43% reduction in ovarian cancer mortality (wHR, 0.57).

Kala Visvanathan, MD, of Johns Hopkins University in Baltimore, and colleagues reported these findings in a poster at the AACR virtual meeting II.

Reductions in ovarian cancer mortality were observed in women who took simvastatin or atorvastatin (wHRs 0.24 and 0.20, respectively), the researchers found.

Lipophilic statin use also was associated with a reduction in ovarian cancer mortality across disease subtypes, although the magnitude of reduction varied. The hazard ratios were 0.60 for high-grade serous ovarian cancer, 0.50 for endometrioid ovarian cancer, 0.20 for clear cell ovarian cancer, 0.30 for mucinous ovarian cancer, and 0.27 for borderline disease.

Survival benefits were evident both in patients who started statins prior to their ovarian cancer diagnosis and in those who started statins after diagnosis.

Never-statin users had a median age of 62 years at baseline, and ever-statin users had a median age of 67 years. The median follow-up was 3.6 years and 5.5 years, respectively.

Data from the registry were linked to prescription claims, and a series of analyses were conducted to examine the association between pre- and postdiagnostic statin use and mortality. The findings were adjusted for age at diagnosis, stage, ovarian cancer subtype, treatments, year of diagnosis, and chronic disease medications. Adherence to statins was greater than 90%.
 

Implications and next steps

The idea of using statins for the treatment of ovarian cancer is appealing because of the promising survival data as well as the broad access, low cost, and tolerability of statins, Dr. Visvanathan said in a statement. About 28% of U.S. adults over age 40 routinely take statins for cholesterol control, and statins are widely used in other countries, she said.

“Our results support research to evaluate the repurposing of therapies that are well tolerated and inexpensive in order to help reduce the global cancer burden,” Dr. Visvanathan and colleagues wrote in their poster.

“Our results provide evidence in support of the evaluation of lipophilic statins, particularly atorvastatin and/or simvastatin, for the treatment of [epithelial ovarian cancer] in conjunction with existing therapies,” the researchers wrote. They added that these statins should be “evaluated in randomized clinical trials that include correlative endpoints.”

Further, the researchers argued that “the results are biologically plausible based on known mechanisms associated with statin use and highlight the fact that statins may be effective to treat more than one disease/outcome (i.e., high cholesterol, EOC [epithelial ovarian cancer], breast cancer).”

The results of this study are intriguing, according to James Yarmolinsky, MSc, of the University of Bristol, England. Mr. Yarmolinsky is the lead author of a case-control study that showed an association between genetically proxied 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibition and lower odds of developing epithelial ovarian cancer (JAMA. 2020;323[7]:646-655).

Mr. Yarmolinsky and colleagues found that HMG-CoA reductase inhibition equivalent to a 38.7-mg/dL reduction in low-density lipoprotein cholesterol was significantly associated with lower odds of epithelial ovarian cancer in the general population (odds ratio, 0.60) and among BRCA1/2 mutation carriers (hazard ratio, 0.69). The findings raised questions about whether a similar association would be seen with medications such as statins that inhibit HMG-CoA reductase.

“These findings linking statin use to lower ovarian cancer mortality are really interesting given our own research suggesting that these drugs may also lower women’s risk of developing this disease in the first place,” Mr. Yarmolinsky said.

“The survival rate for ovarian cancer remains the lowest among all gynecological cancers in the United States, so use of these medications in either a preventive or therapeutic context could offer an important approach for reducing disease burden,” he added. “If the findings reported by Visvanathan and colleagues can be shown to replicate in other large population-based studies, testing the efficacy of statins in a randomized clinical trial could provide definitive evidence of whether these medications lower ovarian cancer mortality.”

The Department of Defense and the Breast Cancer Research Foundation funded the current study. Dr. Visvanathan and Mr. Yarmolinsky reported no disclosures.

[email protected]

SOURCE: Visvanathan K et al. AACR 2020, Abstract 5782.