Female permanent contraception is among the most widely used contraceptive methods worldwide. In the United States, more than 640,000 procedures are performed each year and it is used by 25% of women who use contraception.^1–4 Female permanent contraception is achieved via salpingectomy, tubal interruption, or hysteroscopic techniques.

Essure, the only currently available hysteroscopic permanent contraception device, approved by the US Food and Drug Administration (FDA) in 2002,^5,6 has been implanted in more than 750,000 women worldwide.⁷ Essure was developed by Conceptus Inc, a small medical device company that was acquired by Bayer in 2013. The greatest uptake has been in the United States, which accounts for approximately 80% of procedures worldwide.^7,8

Essure placement involves insertion of a nickel-titanium alloy coil with a stainless-steel inner coil, polyethylene terephthalate fibers, platinum marker bands, and silver-tin solder.⁹ The insert is approximately 4 cm in length and expands to 2 mm in diameter once deployed.⁹

Potential advantages of a hysteroscopic approach are that intra-abdominal surgery can be avoided and the procedure can be performed in an office without the need for general anesthesia.⁷ Due to these potential benefits, hysteroscopic permanent contraception with Essure underwent expedited review and received FDA approval without any comparative trials.^1,5,10 However, there also are disadvantages: the method is not always successfully placed on first attempt and it is not immediately effective. Successful placement rates range between 60% and 98%, most commonly around 90%.^11–15 Additionally, if placement is successful, alternative contraception must be used until a confirmatory radiologic test is performed at least 3 months after the procedure.^9,11 Initially, hysterosalpingography was required to demonstrate a satisfactory insert location and successful tubal occlusion.^11,16 Compliance with this testing is variable, ranging in studies from 13% to 71%.¹¹ As of 2015, transvaginal ultrasonography showing insert retention and location has been approved as an alternative confirmatory method.^9,11,16,17 Evidence suggests that the less invasive ultrasound option increases follow-up rates; while limited, one study noted an increase in follow-up rates from 77.5% for hysterosalpingogram to 88% (P = .008) for transvaginal ultrasound.¹⁸

Recent concerns about potential medical and safety issues have impacted approval status and marketing of hysteroscopic permanent contraception worldwide. In response to safety concerns, the FDA added a boxed safety warning and patient decision checklist in 2016.¹⁹ Bayer withdrew the device from all markets outside of the United States as of May 2017.^20–22 In April 2018, the FDA restricted Essure sales in the United States only to providers and facilities who utilized an FDA-approved checklist to ensure the device met standards for safety and effectiveness.¹⁹ Most recently, Bayer announced that Essure would no longer be sold or distributed in the United States after December 31, 2018 (See “FDA Press Release”).²³

So how did we get here? How did the promise of a “less invasive” approach for female permanent contraception get off course?

A search of the Manufacturer and User Facility Device Experience (MAUDE) database from Essure’s approval date in 2002 to December 2017 revealed 26,773 medical device reports, with more than 90% of those received in 2017 related to device removal.¹⁹ As more complications and complaints have been reported, the lack of comparative data has presented a problem for understanding the relative risk of the procedure as compared with laparoscopic techniques. Additionally, the approval studies lacked information about what happened to women who had an unsuccessful attempted hysteroscopic procedure. Without robust data sets or large trials, early research used evidence-based Markov modeling; findings suggested that hysteroscopic permanent contraception resulted in fewer women achieving successful permanent contraception and that the hysteroscopic procedure was not as effective as laparoscopic occlusion procedures with “typical” use.^24,25

Over the past year, more clinical data have been published comparing hysteroscopic with laparoscopic permanent contraception procedures. In this article, we evaluate this information to help us better understand the relative efficacy and safety of the different permanent contraception methods and review recent articles describing removal techniques to further assist clinicians and patients considering such procedures.

Hysteroscopic versus laparoscopic procedures for permanent contraception

Bouillon K, Bertrand M, Bader G, et al. Association of hysteroscopic vs laparoscopic sterilization with procedural, gynecological, and medical outcomes. JAMA. 2018:319(4):375-387.

Antoun L, Smith P, Gupta J, et al. The feasibility, safety, and effectiveness of hysteroscopic sterilization compared with laparoscopic sterilization. Am J of Obstet Gynecol. 2017;217(5):570.e1-570.e6. doi:10.1016/j.ajog.2017.07.011.

Jokinen E, Heino A, Karipohja T, et al. Safety and effectiveness of female tubal sterilisation by hysteroscopy, laparoscopy, or laparotomy: a register based study. BJOG. 2017;124(12):1851-1857.

In this section, we present 3 recent studies that evaluate pregnancy outcomes and complications including reoperation or second permanent contraception procedure rates.

Data from France measure up to 3-year differences in adverse outcomes

Bouillon and colleagues aimed to identify differences in adverse outcome rates between hysteroscopic and laparoscopic permanent contraceptive methods. Utilizing national hospital discharge data in France, the researchers conducted a large database study review of records from more than 105,000 women aged 30 to 54 years receiving hysteroscopic or laparoscopic permanent contraception between 2010 and 2014. The database contains details based on the ICD-10 codes for all public and private hospitals in France, representing approximately 75% of the total population. Procedures were performed at 831 hospitals in 26 regions.

Adverse outcomes were divided into surgical, medical, and gynecologic complications (TABLE 1) and were assessed at 3 timepoints: at the time of procedure and at 1 and 3 years postprocedure.

Overall, 71,303 women (67.7%) underwent hysteroscopic permanent contraception procedures and 34,054 women (32.3%) underwent laparoscopic permanent contraception procedures. Immediate surgical and medical complications were significantly less common for women having hysteroscopic compared with laparoscopic procedures. Surgical complications at the time of the procedure occurred in 96 (0.13%) and 265 (0.78%) women, respectively (adjusted odds ratio [aOR], 0.18; 95% confidence interval [CI], 0.14-0.23). Medical complications at the time of procedure occurred in 41 (0.06%) and 39 (0.11%) women, respectively (aOR, 0.51; 95% CI, 0.30-0.89).

However, gynecologic outcomes, including need for a second surgery to provide permanent contraception and overall failure rates (need for salpingectomy, a second permanent contraception procedure, or pregnancy) were significantly more common for women having hysteroscopic procedures. By 1 year after the procedure, 2,955 women (4.10%) who initially had a hysteroscopic procedure, and 56 women (0.16%) who had a laparoscopic procedure required a second permanent contraception surgery (adjusted hazard ratio [aHR], 25.99; 95% CI, 17.84-37.86). By the third year, additional procedures were performed in 3,230 (4.5%) and 97 (0.28%) women, respectively (aHR, 16.63; 95% CI, 12.50-22.20). Most (65%) of the repeat procedures were performed laparoscopically. Although pregnancy rates were significantly lower at 1 year among women who initially chose a hysteroscopic procedure (0.24% vs 0.41%; aHR, 0.70; 95% CI, 0.53-0.92), the rates did not differ at 3 years (0.48% vs 0.57%, respectively; aHR, 1.04; 95% CI, 0.83-1.30).

Most importantly, overall procedure failure rates were significantly higher at 1 year in women initially choosing a hysteroscopic approach compared with laparoscopic approach (3,446 [4.83%] vs 235 [0.69%] women; aHR, 7.11; 95% CI, 5.92-8.54). This difference persisted through 3 years (4,098 [5.75%] vs 438 [1.29%] women, respectively; aHR, 4.66; 95% CI, 4.06-5.34).

UK data indicate high reoperation rate for hysteroscopic procedures

Antoun and colleagues aimed to compare pregnancy rates, radiologic imaging follow-up rates, reoperations, and 30-day adverse outcomes, between hysteroscopic and laparoscopic permanent contraception methods. Conducted at a single teaching hospital in the United Kingdom, this study included 3,497 women who underwent procedures between 2005 and 2015. The data were collected prospectively for the 1,085 women who underwent hysteroscopic procedures and retrospectively for 2,412 women who had laparoscopic permanent contraception procedures with the Filshie clip.

Over the 10-year study period, hysteroscopic permanent contraception increased from 14.2% (40 of 280) of procedures in 2005 to 40.5% (150 of 350) of procedures in 2015 (P<.001). Overall, 2,400 women (99.5%) underwent successful laparoscopic permanent contraception, compared with 992 women (91.4%) in the hysteroscopic group (OR, 18.8; 95% CI, 10.2-34.4).

In the hysteroscopic group, 958 women (97%) returned for confirmatory testing, of whom 902 (91% of women with successful placement) underwent satisfactory confirmatory testing. There were 93 (8.6%) unsuccessful placements that were due to inability to visualize ostia or tubal stenosis (n = 72 [77.4%]), patient intolerance to procedure (n = 15 [16.1%]), or device failure (n = 6 [6.5%]).

The odds for reoperation were 6 times greater in the hysteroscopic group by 1 year after surgery (22 [2%] vs 8 [0.3%] women; OR, 6.2; 95% CI, 2.8-14.0). However, the 1-year pregnancy risk was similar between the 2 groups, with 3 reported pregnancies after hysteroscopic permanent contraception and 5 reported pregnancies after laparoscopic permanent contraception (OR, 1.3; 95% CI, 0.3-5.6).

Finnish researchers also find high reoperation rate

Jokinen and colleagues used linked national database registries in Finland to capture data on pregnancy rate and reoperations among 16,272 women who underwent permanent contraception procedures between 2009 and 2014. The authors compared outcomes following hysteroscopic (Essure), laparoscopic (Filshie clip), and postpartum minilaparotomy (Pomeroy) permanent contraception techniques. According to the investigators, the latter method was almost exclusively performed at the time of cesarean delivery. While there was no difference in pregnancy rates, second permanent contraception procedures were significantly greater in the hysteroscopic group compared with the laparoscopic group (TABLE 2).

Technique for hysteroscopic permanent contraception insert removal

Johal T, Kuruba N, Sule M, et al. Laparoscopic salpingectomy and removal of Essure hysteroscopic sterilisation device: a case series. Eur J Contracept Reprod Health Care. 2018;23(3):227-230.

Lazorwitz A, Tocce K. A case series of removal of nickel-titanium sterilization microinserts from the uterine cornua using laparoscopic electrocautery for salpingectomy. Contraception. 2017;96(2):96-98.

As reports of complications and concerns with hysteroscopic permanent contraception increase, there has been a rise in device removal procedures. We present 2 recent articles that review laparoscopic techniques for the removal of hysteroscopic permanent contraception devices and describe subsequent outcomes.

Laparoscopic salpingectomy without insert transection

In this descriptive retrospective study, Johal and colleagues reviewed hysteroscopic permanent contraception insert removal in 8 women between 2015 and 2017. The authors described their laparoscopic salpingectomy approach and perioperative complications. Overall safety and feasibility with laparoscopic salpingectomy were evaluated by identifying the number of procedures requiring intraoperative conversion to laparotomy, cornuectomy, or hysterectomy. The authors also measured operative time, estimated blood loss, length of stay, and incidence of implant fracture.

Indications for insert removal included pain (n = 4), dyspareunia (n = 2), abnormal uterine bleeding (n = 1), and unsuccessful placement or evidence of tubal occlusion failure during confirmatory imaging (n = 4). The surgeons divided the mesosalpinx and then transected the fallopian tube approximately 1 cm distal to the cornua exposing the permanent contraception insert while avoiding direct electrosurgical application to the insert. The inserts were then removed intact with gentle traction. All 8 women underwent laparoscopic removal with salpingectomy. One patient had a surgical complication of serosal bowel injury due to laparoscopic entry that was repaired in the usual fashion. Operative time averaged 65 minutes (range, 30 to 100 minutes), blood loss was minimal, and there were no implant fractures.

Laparoscopic salpingectomy with insert transection

In this case series, Lazorwitz and Tocce described the use of laparoscopic salpingectomy for hysteroscopic permanent contraception insert removal in 20 women between 2011 and 2017. The authors described their surgical technique, which included division of the mesosalpinx followed by transection of the fallopian tube about 0.5 to 1 cm distal to the cornua. This process often resulted in transection of the insert, and the remaining insert was grasped and removed with gentle traction. If removal of the insert was incomplete, hysteroscopy was performed to identify remaining parts.

Indications for removal included pelvic pain (n = 14), abnormal uterine bleeding (n = 2), rash (n = 1), and unsuccessful placement or evidence of tubal occlusion failure during confirmatory imaging (n = 6). Three women underwent additional diagnostic hysteroscopy for retained implant fragments after laparoscopic salpingectomy. Fragments in all 3 women were 1 to 3 mm in size and left in situ as they were unable to be removed or located hysteroscopically. There were no reported postoperative complications including injury, infection, or readmission within 30 days of salpingectomy.

Shift in method use

Hysteroscopic permanent contraception procedures have low immediate surgical and medical complication rates but result in a high rate of reoperation to achieve the desired outcome.  Notably, the largest available comparative trials are from Europe, which may affect the generalizability to US providers, patients, and health care systems.

Importantly, since the introduction of hysteroscopic permanent contraception in 2002, the landscape of contraception has changed in the United States. Contraception use has shifted to fewer permanent procedures and more high-efficacy reversible options. Overall, reliance on female permanent contraception has been declining in the United States, accounting for 17.8% of contracepting women in 1995 and 15.5% in 2013.^27,28 Permanent contraception has begun shifting from tubal interruption to salpingectomy as mounting evidence has demonstrated up to a 65% reduction in a woman's lifetime risk of ovarian cancer.^29-32 A recent study from a large Northern California integrated health system reported an increase in salpingectomy for permanent contraception from 1% of interval procedures in 2011 to 78% in 2016.³³

Long-acting reversible contraceptive (LARC) methods are also becoming more prevalent and are used by 7.2% of women using contraception in the United States.^28,34 Typical use pregnancy rates with the levonorgestrel 52-mg intrauterine system, etonogestrel implant, and copper T380A intrauterine device are 0.2%, 0.2%, and 0.4% in the first year, respectively.^35,37 These rates are about the same as those reported for Essure in the articles presented here.^13,26 Because these methods are easily placed in the office and are immediately effective, their increased availability over the past decade changes demand for a permanent contraceptive procedure.

Essure underwent expedited FDA review because it had the potential to fill a contraceptive void--it was considered permanent, highly efficacious, low risk, and accessible to women regardless of health comorbidities or access to hospital operating rooms. The removal of Essure from the market is not only the result of a collection of problem reports (relatively small given the overall number of women who have used the device) but also the aggregate result of a changing marketplace and the differential needs of pharmaceutical companies and patients.

For a hysteroscopic permanent contraception insert to survive as a marketed product, the company needs high volume use. However, the increase in LARC provision and permanent contraceptive procedures using opportunistic salpingectomy have matured the market away from the presently available hysteroscopic method. This technology, in its current form, is ideal for women desiring permanent contraception but who have a contraindication to laparoscopic surgery, or for women who can access an office procedure in their community but lack access to a hospital-based procedure. For a pharmaceutical company, that smaller market may not be enough. However, the technology itself is still vital, and future development should focus on what we have learned; the ideal product should be immediately effective, not require a follow-up confirmation test, and not leave permanent foreign body within the uterus or tube.

Share your thoughts! Send your Letter to the Editor to rbarbieri@mdedge.com. Please include your name and the city and state in which you practice.

Female permanent contraception is among the most widely used contraceptive methods worldwide. In the United States, more than 640,000 procedures are performed each year and it is used by 25% of women who use contraception.^1–4 Female permanent contraception is achieved via salpingectomy, tubal interruption, or hysteroscopic techniques.

Essure, the only currently available hysteroscopic permanent contraception device, approved by the US Food and Drug Administration (FDA) in 2002,^5,6 has been implanted in more than 750,000 women worldwide.⁷ Essure was developed by Conceptus Inc, a small medical device company that was acquired by Bayer in 2013. The greatest uptake has been in the United States, which accounts for approximately 80% of procedures worldwide.^7,8

Essure placement involves insertion of a nickel-titanium alloy coil with a stainless-steel inner coil, polyethylene terephthalate fibers, platinum marker bands, and silver-tin solder.⁹ The insert is approximately 4 cm in length and expands to 2 mm in diameter once deployed.⁹

Potential advantages of a hysteroscopic approach are that intra-abdominal surgery can be avoided and the procedure can be performed in an office without the need for general anesthesia.⁷ Due to these potential benefits, hysteroscopic permanent contraception with Essure underwent expedited review and received FDA approval without any comparative trials.^1,5,10 However, there also are disadvantages: the method is not always successfully placed on first attempt and it is not immediately effective. Successful placement rates range between 60% and 98%, most commonly around 90%.^11–15 Additionally, if placement is successful, alternative contraception must be used until a confirmatory radiologic test is performed at least 3 months after the procedure.^9,11 Initially, hysterosalpingography was required to demonstrate a satisfactory insert location and successful tubal occlusion.^11,16 Compliance with this testing is variable, ranging in studies from 13% to 71%.¹¹ As of 2015, transvaginal ultrasonography showing insert retention and location has been approved as an alternative confirmatory method.^9,11,16,17 Evidence suggests that the less invasive ultrasound option increases follow-up rates; while limited, one study noted an increase in follow-up rates from 77.5% for hysterosalpingogram to 88% (P = .008) for transvaginal ultrasound.¹⁸

Recent concerns about potential medical and safety issues have impacted approval status and marketing of hysteroscopic permanent contraception worldwide. In response to safety concerns, the FDA added a boxed safety warning and patient decision checklist in 2016.¹⁹ Bayer withdrew the device from all markets outside of the United States as of May 2017.^20–22 In April 2018, the FDA restricted Essure sales in the United States only to providers and facilities who utilized an FDA-approved checklist to ensure the device met standards for safety and effectiveness.¹⁹ Most recently, Bayer announced that Essure would no longer be sold or distributed in the United States after December 31, 2018 (See “FDA Press Release”).²³

So how did we get here? How did the promise of a “less invasive” approach for female permanent contraception get off course?

A search of the Manufacturer and User Facility Device Experience (MAUDE) database from Essure’s approval date in 2002 to December 2017 revealed 26,773 medical device reports, with more than 90% of those received in 2017 related to device removal.¹⁹ As more complications and complaints have been reported, the lack of comparative data has presented a problem for understanding the relative risk of the procedure as compared with laparoscopic techniques. Additionally, the approval studies lacked information about what happened to women who had an unsuccessful attempted hysteroscopic procedure. Without robust data sets or large trials, early research used evidence-based Markov modeling; findings suggested that hysteroscopic permanent contraception resulted in fewer women achieving successful permanent contraception and that the hysteroscopic procedure was not as effective as laparoscopic occlusion procedures with “typical” use.^24,25

Over the past year, more clinical data have been published comparing hysteroscopic with laparoscopic permanent contraception procedures. In this article, we evaluate this information to help us better understand the relative efficacy and safety of the different permanent contraception methods and review recent articles describing removal techniques to further assist clinicians and patients considering such procedures.

Hysteroscopic versus laparoscopic procedures for permanent contraception

Bouillon K, Bertrand M, Bader G, et al. Association of hysteroscopic vs laparoscopic sterilization with procedural, gynecological, and medical outcomes. JAMA. 2018:319(4):375-387.

Antoun L, Smith P, Gupta J, et al. The feasibility, safety, and effectiveness of hysteroscopic sterilization compared with laparoscopic sterilization. Am J of Obstet Gynecol. 2017;217(5):570.e1-570.e6. doi:10.1016/j.ajog.2017.07.011.

Jokinen E, Heino A, Karipohja T, et al. Safety and effectiveness of female tubal sterilisation by hysteroscopy, laparoscopy, or laparotomy: a register based study. BJOG. 2017;124(12):1851-1857.

In this section, we present 3 recent studies that evaluate pregnancy outcomes and complications including reoperation or second permanent contraception procedure rates.

Data from France measure up to 3-year differences in adverse outcomes

Bouillon and colleagues aimed to identify differences in adverse outcome rates between hysteroscopic and laparoscopic permanent contraceptive methods. Utilizing national hospital discharge data in France, the researchers conducted a large database study review of records from more than 105,000 women aged 30 to 54 years receiving hysteroscopic or laparoscopic permanent contraception between 2010 and 2014. The database contains details based on the ICD-10 codes for all public and private hospitals in France, representing approximately 75% of the total population. Procedures were performed at 831 hospitals in 26 regions.

Adverse outcomes were divided into surgical, medical, and gynecologic complications (TABLE 1) and were assessed at 3 timepoints: at the time of procedure and at 1 and 3 years postprocedure.

Overall, 71,303 women (67.7%) underwent hysteroscopic permanent contraception procedures and 34,054 women (32.3%) underwent laparoscopic permanent contraception procedures. Immediate surgical and medical complications were significantly less common for women having hysteroscopic compared with laparoscopic procedures. Surgical complications at the time of the procedure occurred in 96 (0.13%) and 265 (0.78%) women, respectively (adjusted odds ratio [aOR], 0.18; 95% confidence interval [CI], 0.14-0.23). Medical complications at the time of procedure occurred in 41 (0.06%) and 39 (0.11%) women, respectively (aOR, 0.51; 95% CI, 0.30-0.89).

However, gynecologic outcomes, including need for a second surgery to provide permanent contraception and overall failure rates (need for salpingectomy, a second permanent contraception procedure, or pregnancy) were significantly more common for women having hysteroscopic procedures. By 1 year after the procedure, 2,955 women (4.10%) who initially had a hysteroscopic procedure, and 56 women (0.16%) who had a laparoscopic procedure required a second permanent contraception surgery (adjusted hazard ratio [aHR], 25.99; 95% CI, 17.84-37.86). By the third year, additional procedures were performed in 3,230 (4.5%) and 97 (0.28%) women, respectively (aHR, 16.63; 95% CI, 12.50-22.20). Most (65%) of the repeat procedures were performed laparoscopically. Although pregnancy rates were significantly lower at 1 year among women who initially chose a hysteroscopic procedure (0.24% vs 0.41%; aHR, 0.70; 95% CI, 0.53-0.92), the rates did not differ at 3 years (0.48% vs 0.57%, respectively; aHR, 1.04; 95% CI, 0.83-1.30).

Most importantly, overall procedure failure rates were significantly higher at 1 year in women initially choosing a hysteroscopic approach compared with laparoscopic approach (3,446 [4.83%] vs 235 [0.69%] women; aHR, 7.11; 95% CI, 5.92-8.54). This difference persisted through 3 years (4,098 [5.75%] vs 438 [1.29%] women, respectively; aHR, 4.66; 95% CI, 4.06-5.34).

UK data indicate high reoperation rate for hysteroscopic procedures

Antoun and colleagues aimed to compare pregnancy rates, radiologic imaging follow-up rates, reoperations, and 30-day adverse outcomes, between hysteroscopic and laparoscopic permanent contraception methods. Conducted at a single teaching hospital in the United Kingdom, this study included 3,497 women who underwent procedures between 2005 and 2015. The data were collected prospectively for the 1,085 women who underwent hysteroscopic procedures and retrospectively for 2,412 women who had laparoscopic permanent contraception procedures with the Filshie clip.

Over the 10-year study period, hysteroscopic permanent contraception increased from 14.2% (40 of 280) of procedures in 2005 to 40.5% (150 of 350) of procedures in 2015 (P<.001). Overall, 2,400 women (99.5%) underwent successful laparoscopic permanent contraception, compared with 992 women (91.4%) in the hysteroscopic group (OR, 18.8; 95% CI, 10.2-34.4).

In the hysteroscopic group, 958 women (97%) returned for confirmatory testing, of whom 902 (91% of women with successful placement) underwent satisfactory confirmatory testing. There were 93 (8.6%) unsuccessful placements that were due to inability to visualize ostia or tubal stenosis (n = 72 [77.4%]), patient intolerance to procedure (n = 15 [16.1%]), or device failure (n = 6 [6.5%]).

The odds for reoperation were 6 times greater in the hysteroscopic group by 1 year after surgery (22 [2%] vs 8 [0.3%] women; OR, 6.2; 95% CI, 2.8-14.0). However, the 1-year pregnancy risk was similar between the 2 groups, with 3 reported pregnancies after hysteroscopic permanent contraception and 5 reported pregnancies after laparoscopic permanent contraception (OR, 1.3; 95% CI, 0.3-5.6).

Finnish researchers also find high reoperation rate

Jokinen and colleagues used linked national database registries in Finland to capture data on pregnancy rate and reoperations among 16,272 women who underwent permanent contraception procedures between 2009 and 2014. The authors compared outcomes following hysteroscopic (Essure), laparoscopic (Filshie clip), and postpartum minilaparotomy (Pomeroy) permanent contraception techniques. According to the investigators, the latter method was almost exclusively performed at the time of cesarean delivery. While there was no difference in pregnancy rates, second permanent contraception procedures were significantly greater in the hysteroscopic group compared with the laparoscopic group (TABLE 2).

Technique for hysteroscopic permanent contraception insert removal

Johal T, Kuruba N, Sule M, et al. Laparoscopic salpingectomy and removal of Essure hysteroscopic sterilisation device: a case series. Eur J Contracept Reprod Health Care. 2018;23(3):227-230.

Lazorwitz A, Tocce K. A case series of removal of nickel-titanium sterilization microinserts from the uterine cornua using laparoscopic electrocautery for salpingectomy. Contraception. 2017;96(2):96-98.

As reports of complications and concerns with hysteroscopic permanent contraception increase, there has been a rise in device removal procedures. We present 2 recent articles that review laparoscopic techniques for the removal of hysteroscopic permanent contraception devices and describe subsequent outcomes.

Laparoscopic salpingectomy without insert transection

In this descriptive retrospective study, Johal and colleagues reviewed hysteroscopic permanent contraception insert removal in 8 women between 2015 and 2017. The authors described their laparoscopic salpingectomy approach and perioperative complications. Overall safety and feasibility with laparoscopic salpingectomy were evaluated by identifying the number of procedures requiring intraoperative conversion to laparotomy, cornuectomy, or hysterectomy. The authors also measured operative time, estimated blood loss, length of stay, and incidence of implant fracture.

Indications for insert removal included pain (n = 4), dyspareunia (n = 2), abnormal uterine bleeding (n = 1), and unsuccessful placement or evidence of tubal occlusion failure during confirmatory imaging (n = 4). The surgeons divided the mesosalpinx and then transected the fallopian tube approximately 1 cm distal to the cornua exposing the permanent contraception insert while avoiding direct electrosurgical application to the insert. The inserts were then removed intact with gentle traction. All 8 women underwent laparoscopic removal with salpingectomy. One patient had a surgical complication of serosal bowel injury due to laparoscopic entry that was repaired in the usual fashion. Operative time averaged 65 minutes (range, 30 to 100 minutes), blood loss was minimal, and there were no implant fractures.

Laparoscopic salpingectomy with insert transection

In this case series, Lazorwitz and Tocce described the use of laparoscopic salpingectomy for hysteroscopic permanent contraception insert removal in 20 women between 2011 and 2017. The authors described their surgical technique, which included division of the mesosalpinx followed by transection of the fallopian tube about 0.5 to 1 cm distal to the cornua. This process often resulted in transection of the insert, and the remaining insert was grasped and removed with gentle traction. If removal of the insert was incomplete, hysteroscopy was performed to identify remaining parts.

Indications for removal included pelvic pain (n = 14), abnormal uterine bleeding (n = 2), rash (n = 1), and unsuccessful placement or evidence of tubal occlusion failure during confirmatory imaging (n = 6). Three women underwent additional diagnostic hysteroscopy for retained implant fragments after laparoscopic salpingectomy. Fragments in all 3 women were 1 to 3 mm in size and left in situ as they were unable to be removed or located hysteroscopically. There were no reported postoperative complications including injury, infection, or readmission within 30 days of salpingectomy.

Shift in method use

Hysteroscopic permanent contraception procedures have low immediate surgical and medical complication rates but result in a high rate of reoperation to achieve the desired outcome.  Notably, the largest available comparative trials are from Europe, which may affect the generalizability to US providers, patients, and health care systems.

Importantly, since the introduction of hysteroscopic permanent contraception in 2002, the landscape of contraception has changed in the United States. Contraception use has shifted to fewer permanent procedures and more high-efficacy reversible options. Overall, reliance on female permanent contraception has been declining in the United States, accounting for 17.8% of contracepting women in 1995 and 15.5% in 2013.^27,28 Permanent contraception has begun shifting from tubal interruption to salpingectomy as mounting evidence has demonstrated up to a 65% reduction in a woman's lifetime risk of ovarian cancer.^29-32 A recent study from a large Northern California integrated health system reported an increase in salpingectomy for permanent contraception from 1% of interval procedures in 2011 to 78% in 2016.³³

Long-acting reversible contraceptive (LARC) methods are also becoming more prevalent and are used by 7.2% of women using contraception in the United States.^28,34 Typical use pregnancy rates with the levonorgestrel 52-mg intrauterine system, etonogestrel implant, and copper T380A intrauterine device are 0.2%, 0.2%, and 0.4% in the first year, respectively.^35,37 These rates are about the same as those reported for Essure in the articles presented here.^13,26 Because these methods are easily placed in the office and are immediately effective, their increased availability over the past decade changes demand for a permanent contraceptive procedure.

Essure underwent expedited FDA review because it had the potential to fill a contraceptive void--it was considered permanent, highly efficacious, low risk, and accessible to women regardless of health comorbidities or access to hospital operating rooms. The removal of Essure from the market is not only the result of a collection of problem reports (relatively small given the overall number of women who have used the device) but also the aggregate result of a changing marketplace and the differential needs of pharmaceutical companies and patients.

For a hysteroscopic permanent contraception insert to survive as a marketed product, the company needs high volume use. However, the increase in LARC provision and permanent contraceptive procedures using opportunistic salpingectomy have matured the market away from the presently available hysteroscopic method. This technology, in its current form, is ideal for women desiring permanent contraception but who have a contraindication to laparoscopic surgery, or for women who can access an office procedure in their community but lack access to a hospital-based procedure. For a pharmaceutical company, that smaller market may not be enough. However, the technology itself is still vital, and future development should focus on what we have learned; the ideal product should be immediately effective, not require a follow-up confirmation test, and not leave permanent foreign body within the uterus or tube.

Share your thoughts! Send your Letter to the Editor to rbarbieri@mdedge.com. Please include your name and the city and state in which you practice.

Female permanent contraception is among the most widely used contraceptive methods worldwide. In the United States, more than 640,000 procedures are performed each year and it is used by 25% of women who use contraception.^1–4 Female permanent contraception is achieved via salpingectomy, tubal interruption, or hysteroscopic techniques.

Essure, the only currently available hysteroscopic permanent contraception device, approved by the US Food and Drug Administration (FDA) in 2002,^5,6 has been implanted in more than 750,000 women worldwide.⁷ Essure was developed by Conceptus Inc, a small medical device company that was acquired by Bayer in 2013. The greatest uptake has been in the United States, which accounts for approximately 80% of procedures worldwide.^7,8

Essure placement involves insertion of a nickel-titanium alloy coil with a stainless-steel inner coil, polyethylene terephthalate fibers, platinum marker bands, and silver-tin solder.⁹ The insert is approximately 4 cm in length and expands to 2 mm in diameter once deployed.⁹

Potential advantages of a hysteroscopic approach are that intra-abdominal surgery can be avoided and the procedure can be performed in an office without the need for general anesthesia.⁷ Due to these potential benefits, hysteroscopic permanent contraception with Essure underwent expedited review and received FDA approval without any comparative trials.^1,5,10 However, there also are disadvantages: the method is not always successfully placed on first attempt and it is not immediately effective. Successful placement rates range between 60% and 98%, most commonly around 90%.^11–15 Additionally, if placement is successful, alternative contraception must be used until a confirmatory radiologic test is performed at least 3 months after the procedure.^9,11 Initially, hysterosalpingography was required to demonstrate a satisfactory insert location and successful tubal occlusion.^11,16 Compliance with this testing is variable, ranging in studies from 13% to 71%.¹¹ As of 2015, transvaginal ultrasonography showing insert retention and location has been approved as an alternative confirmatory method.^9,11,16,17 Evidence suggests that the less invasive ultrasound option increases follow-up rates; while limited, one study noted an increase in follow-up rates from 77.5% for hysterosalpingogram to 88% (P = .008) for transvaginal ultrasound.¹⁸

Recent concerns about potential medical and safety issues have impacted approval status and marketing of hysteroscopic permanent contraception worldwide. In response to safety concerns, the FDA added a boxed safety warning and patient decision checklist in 2016.¹⁹ Bayer withdrew the device from all markets outside of the United States as of May 2017.^20–22 In April 2018, the FDA restricted Essure sales in the United States only to providers and facilities who utilized an FDA-approved checklist to ensure the device met standards for safety and effectiveness.¹⁹ Most recently, Bayer announced that Essure would no longer be sold or distributed in the United States after December 31, 2018 (See “FDA Press Release”).²³

So how did we get here? How did the promise of a “less invasive” approach for female permanent contraception get off course?

A search of the Manufacturer and User Facility Device Experience (MAUDE) database from Essure’s approval date in 2002 to December 2017 revealed 26,773 medical device reports, with more than 90% of those received in 2017 related to device removal.¹⁹ As more complications and complaints have been reported, the lack of comparative data has presented a problem for understanding the relative risk of the procedure as compared with laparoscopic techniques. Additionally, the approval studies lacked information about what happened to women who had an unsuccessful attempted hysteroscopic procedure. Without robust data sets or large trials, early research used evidence-based Markov modeling; findings suggested that hysteroscopic permanent contraception resulted in fewer women achieving successful permanent contraception and that the hysteroscopic procedure was not as effective as laparoscopic occlusion procedures with “typical” use.^24,25

Over the past year, more clinical data have been published comparing hysteroscopic with laparoscopic permanent contraception procedures. In this article, we evaluate this information to help us better understand the relative efficacy and safety of the different permanent contraception methods and review recent articles describing removal techniques to further assist clinicians and patients considering such procedures.

Hysteroscopic versus laparoscopic procedures for permanent contraception

Bouillon K, Bertrand M, Bader G, et al. Association of hysteroscopic vs laparoscopic sterilization with procedural, gynecological, and medical outcomes. JAMA. 2018:319(4):375-387.

Antoun L, Smith P, Gupta J, et al. The feasibility, safety, and effectiveness of hysteroscopic sterilization compared with laparoscopic sterilization. Am J of Obstet Gynecol. 2017;217(5):570.e1-570.e6. doi:10.1016/j.ajog.2017.07.011.

Jokinen E, Heino A, Karipohja T, et al. Safety and effectiveness of female tubal sterilisation by hysteroscopy, laparoscopy, or laparotomy: a register based study. BJOG. 2017;124(12):1851-1857.

In this section, we present 3 recent studies that evaluate pregnancy outcomes and complications including reoperation or second permanent contraception procedure rates.

Data from France measure up to 3-year differences in adverse outcomes

Bouillon and colleagues aimed to identify differences in adverse outcome rates between hysteroscopic and laparoscopic permanent contraceptive methods. Utilizing national hospital discharge data in France, the researchers conducted a large database study review of records from more than 105,000 women aged 30 to 54 years receiving hysteroscopic or laparoscopic permanent contraception between 2010 and 2014. The database contains details based on the ICD-10 codes for all public and private hospitals in France, representing approximately 75% of the total population. Procedures were performed at 831 hospitals in 26 regions.

Adverse outcomes were divided into surgical, medical, and gynecologic complications (TABLE 1) and were assessed at 3 timepoints: at the time of procedure and at 1 and 3 years postprocedure.

Overall, 71,303 women (67.7%) underwent hysteroscopic permanent contraception procedures and 34,054 women (32.3%) underwent laparoscopic permanent contraception procedures. Immediate surgical and medical complications were significantly less common for women having hysteroscopic compared with laparoscopic procedures. Surgical complications at the time of the procedure occurred in 96 (0.13%) and 265 (0.78%) women, respectively (adjusted odds ratio [aOR], 0.18; 95% confidence interval [CI], 0.14-0.23). Medical complications at the time of procedure occurred in 41 (0.06%) and 39 (0.11%) women, respectively (aOR, 0.51; 95% CI, 0.30-0.89).

However, gynecologic outcomes, including need for a second surgery to provide permanent contraception and overall failure rates (need for salpingectomy, a second permanent contraception procedure, or pregnancy) were significantly more common for women having hysteroscopic procedures. By 1 year after the procedure, 2,955 women (4.10%) who initially had a hysteroscopic procedure, and 56 women (0.16%) who had a laparoscopic procedure required a second permanent contraception surgery (adjusted hazard ratio [aHR], 25.99; 95% CI, 17.84-37.86). By the third year, additional procedures were performed in 3,230 (4.5%) and 97 (0.28%) women, respectively (aHR, 16.63; 95% CI, 12.50-22.20). Most (65%) of the repeat procedures were performed laparoscopically. Although pregnancy rates were significantly lower at 1 year among women who initially chose a hysteroscopic procedure (0.24% vs 0.41%; aHR, 0.70; 95% CI, 0.53-0.92), the rates did not differ at 3 years (0.48% vs 0.57%, respectively; aHR, 1.04; 95% CI, 0.83-1.30).

Most importantly, overall procedure failure rates were significantly higher at 1 year in women initially choosing a hysteroscopic approach compared with laparoscopic approach (3,446 [4.83%] vs 235 [0.69%] women; aHR, 7.11; 95% CI, 5.92-8.54). This difference persisted through 3 years (4,098 [5.75%] vs 438 [1.29%] women, respectively; aHR, 4.66; 95% CI, 4.06-5.34).

UK data indicate high reoperation rate for hysteroscopic procedures

Antoun and colleagues aimed to compare pregnancy rates, radiologic imaging follow-up rates, reoperations, and 30-day adverse outcomes, between hysteroscopic and laparoscopic permanent contraception methods. Conducted at a single teaching hospital in the United Kingdom, this study included 3,497 women who underwent procedures between 2005 and 2015. The data were collected prospectively for the 1,085 women who underwent hysteroscopic procedures and retrospectively for 2,412 women who had laparoscopic permanent contraception procedures with the Filshie clip.

Over the 10-year study period, hysteroscopic permanent contraception increased from 14.2% (40 of 280) of procedures in 2005 to 40.5% (150 of 350) of procedures in 2015 (P<.001). Overall, 2,400 women (99.5%) underwent successful laparoscopic permanent contraception, compared with 992 women (91.4%) in the hysteroscopic group (OR, 18.8; 95% CI, 10.2-34.4).

In the hysteroscopic group, 958 women (97%) returned for confirmatory testing, of whom 902 (91% of women with successful placement) underwent satisfactory confirmatory testing. There were 93 (8.6%) unsuccessful placements that were due to inability to visualize ostia or tubal stenosis (n = 72 [77.4%]), patient intolerance to procedure (n = 15 [16.1%]), or device failure (n = 6 [6.5%]).

The odds for reoperation were 6 times greater in the hysteroscopic group by 1 year after surgery (22 [2%] vs 8 [0.3%] women; OR, 6.2; 95% CI, 2.8-14.0). However, the 1-year pregnancy risk was similar between the 2 groups, with 3 reported pregnancies after hysteroscopic permanent contraception and 5 reported pregnancies after laparoscopic permanent contraception (OR, 1.3; 95% CI, 0.3-5.6).

Finnish researchers also find high reoperation rate

Jokinen and colleagues used linked national database registries in Finland to capture data on pregnancy rate and reoperations among 16,272 women who underwent permanent contraception procedures between 2009 and 2014. The authors compared outcomes following hysteroscopic (Essure), laparoscopic (Filshie clip), and postpartum minilaparotomy (Pomeroy) permanent contraception techniques. According to the investigators, the latter method was almost exclusively performed at the time of cesarean delivery. While there was no difference in pregnancy rates, second permanent contraception procedures were significantly greater in the hysteroscopic group compared with the laparoscopic group (TABLE 2).

Technique for hysteroscopic permanent contraception insert removal

Johal T, Kuruba N, Sule M, et al. Laparoscopic salpingectomy and removal of Essure hysteroscopic sterilisation device: a case series. Eur J Contracept Reprod Health Care. 2018;23(3):227-230.

Lazorwitz A, Tocce K. A case series of removal of nickel-titanium sterilization microinserts from the uterine cornua using laparoscopic electrocautery for salpingectomy. Contraception. 2017;96(2):96-98.

As reports of complications and concerns with hysteroscopic permanent contraception increase, there has been a rise in device removal procedures. We present 2 recent articles that review laparoscopic techniques for the removal of hysteroscopic permanent contraception devices and describe subsequent outcomes.

Laparoscopic salpingectomy without insert transection

In this descriptive retrospective study, Johal and colleagues reviewed hysteroscopic permanent contraception insert removal in 8 women between 2015 and 2017. The authors described their laparoscopic salpingectomy approach and perioperative complications. Overall safety and feasibility with laparoscopic salpingectomy were evaluated by identifying the number of procedures requiring intraoperative conversion to laparotomy, cornuectomy, or hysterectomy. The authors also measured operative time, estimated blood loss, length of stay, and incidence of implant fracture.

Indications for insert removal included pain (n = 4), dyspareunia (n = 2), abnormal uterine bleeding (n = 1), and unsuccessful placement or evidence of tubal occlusion failure during confirmatory imaging (n = 4). The surgeons divided the mesosalpinx and then transected the fallopian tube approximately 1 cm distal to the cornua exposing the permanent contraception insert while avoiding direct electrosurgical application to the insert. The inserts were then removed intact with gentle traction. All 8 women underwent laparoscopic removal with salpingectomy. One patient had a surgical complication of serosal bowel injury due to laparoscopic entry that was repaired in the usual fashion. Operative time averaged 65 minutes (range, 30 to 100 minutes), blood loss was minimal, and there were no implant fractures.

Laparoscopic salpingectomy with insert transection

In this case series, Lazorwitz and Tocce described the use of laparoscopic salpingectomy for hysteroscopic permanent contraception insert removal in 20 women between 2011 and 2017. The authors described their surgical technique, which included division of the mesosalpinx followed by transection of the fallopian tube about 0.5 to 1 cm distal to the cornua. This process often resulted in transection of the insert, and the remaining insert was grasped and removed with gentle traction. If removal of the insert was incomplete, hysteroscopy was performed to identify remaining parts.

Indications for removal included pelvic pain (n = 14), abnormal uterine bleeding (n = 2), rash (n = 1), and unsuccessful placement or evidence of tubal occlusion failure during confirmatory imaging (n = 6). Three women underwent additional diagnostic hysteroscopy for retained implant fragments after laparoscopic salpingectomy. Fragments in all 3 women were 1 to 3 mm in size and left in situ as they were unable to be removed or located hysteroscopically. There were no reported postoperative complications including injury, infection, or readmission within 30 days of salpingectomy.

Shift in method use

Hysteroscopic permanent contraception procedures have low immediate surgical and medical complication rates but result in a high rate of reoperation to achieve the desired outcome.  Notably, the largest available comparative trials are from Europe, which may affect the generalizability to US providers, patients, and health care systems.

Importantly, since the introduction of hysteroscopic permanent contraception in 2002, the landscape of contraception has changed in the United States. Contraception use has shifted to fewer permanent procedures and more high-efficacy reversible options. Overall, reliance on female permanent contraception has been declining in the United States, accounting for 17.8% of contracepting women in 1995 and 15.5% in 2013.^27,28 Permanent contraception has begun shifting from tubal interruption to salpingectomy as mounting evidence has demonstrated up to a 65% reduction in a woman's lifetime risk of ovarian cancer.^29-32 A recent study from a large Northern California integrated health system reported an increase in salpingectomy for permanent contraception from 1% of interval procedures in 2011 to 78% in 2016.³³

Long-acting reversible contraceptive (LARC) methods are also becoming more prevalent and are used by 7.2% of women using contraception in the United States.^28,34 Typical use pregnancy rates with the levonorgestrel 52-mg intrauterine system, etonogestrel implant, and copper T380A intrauterine device are 0.2%, 0.2%, and 0.4% in the first year, respectively.^35,37 These rates are about the same as those reported for Essure in the articles presented here.^13,26 Because these methods are easily placed in the office and are immediately effective, their increased availability over the past decade changes demand for a permanent contraceptive procedure.

Essure underwent expedited FDA review because it had the potential to fill a contraceptive void--it was considered permanent, highly efficacious, low risk, and accessible to women regardless of health comorbidities or access to hospital operating rooms. The removal of Essure from the market is not only the result of a collection of problem reports (relatively small given the overall number of women who have used the device) but also the aggregate result of a changing marketplace and the differential needs of pharmaceutical companies and patients.

For a hysteroscopic permanent contraception insert to survive as a marketed product, the company needs high volume use. However, the increase in LARC provision and permanent contraceptive procedures using opportunistic salpingectomy have matured the market away from the presently available hysteroscopic method. This technology, in its current form, is ideal for women desiring permanent contraception but who have a contraindication to laparoscopic surgery, or for women who can access an office procedure in their community but lack access to a hospital-based procedure. For a pharmaceutical company, that smaller market may not be enough. However, the technology itself is still vital, and future development should focus on what we have learned; the ideal product should be immediately effective, not require a follow-up confirmation test, and not leave permanent foreign body within the uterus or tube.

Share your thoughts! Send your Letter to the Editor to rbarbieri@mdedge.com. Please include your name and the city and state in which you practice.

CASE Onset of nausea and headache, and elevated BP, at full term

A 24-year-old woman (G1P0) at 39 2/7 weeks of gestation without significant medical history and with uncomplicated prenatal care presents to labor and delivery reporting uterine contractions. She reports nausea and vomiting, and reports having a severe headache this morning. Blood pressure (BP) is 154/98 mm Hg. Urine dipstick analysis demonstrates absence of protein.

How should this patient be managed?

Although we have gained a greater understanding of hypertensive disorders in pregnancy—most notably, preeclampsia—during the past 15 years, management of these patients can, as evidenced in the case above, be complicated. Providers must respect this disease and be cognizant of the significant maternal, fetal, and neonatal complications that can be associated with hypertension during pregnancy—a leading cause of preterm birth and maternal mortality in the United States.^1-3 Initiation of early and aggressive antihypertensive medical therapy, when indicated, plays a key role in preventing catastrophic complications of this disease.

Terminology and classification

Hypertension of pregnancy is classified as:

• chronic hypertension: BP≥140/90 mm Hg prior to pregnancy or prior to 20 weeks of gestation. Patients who have persistently elevated BP 12 weeks after delivery are also in this category.
• preeclampsia–eclampsia: hypertension along with multisystem involvement that occurs after 20 weeks of gestation.
• gestational hypertension: hypertension alone after 20 weeks of gestation; in approximately 15% to 25% of these patients, a diagnosis of preeclampsia will be made as pregnancy progresses.
• chronic hypertension with superimposed preeclampsia: hypertension complicated by development of multisystem involvement during the course of the pregnancy—often a challenging diagnosis, associated with greater perinatal morbidity than either chronic hypertension or preeclampsia alone.

Evaluation of the hypertensive gravida

Although most pregnant patients (approximately 90%) who have a diagnosis of chronic hypertension have primary or essential hypertension, a secondary cause—including thyroid disease, systemic lupus erythematosus (SLE), and underlying renal disease—might be present and should be sought out. It is important, therefore, to obtain a comprehensive history along with a directed physical examination and appropriate laboratory tests.

Ideally, a patient with chronic hypertension should be evaluated prior to pregnancy, but this rarely occurs. At the initial encounter, the patient should be informed of risks associated with chronic hypertension, as well as receive education on the signs and symptoms of preeclampsia. Obtain a thorough history—not only to evaluate for secondary causes of hypertension or end-organ involvement (eg, kidney disease), but to identify comorbidities (such as pregestational diabetes mellitus). The patient should be instructed to immediately discontinue any teratogenic medication (such as an angiotensin-converting enzyme inhibitor or angiotensin-receptor blocker).

Routine laboratory evaluation

Testing should comprise a chemistry panel to evaluate serum creatinine, electrolytes, and liver enzymes. A 24-hour urine collection for protein excretion and creatinine clearance or a urine protein–creatinine ratio should be obtained to record baseline kidney function.⁴ (Such testing is important, given that new-onset or worsening proteinuria is a manifestation of superimposed preeclampsia.) All pregnant patients with chronic hypertension also should have a complete blood count, including a platelet count, and an early screen for gestational diabetes.

Depending on what information is obtained from the history and physical examination, renal ultrasonography and any of several laboratory tests can be ordered, including thyroid function, an SLE panel, and vanillylmandelic acid/metanephrines. If the patient has a history of severe hypertension for greater than 5 years, is older than 40 years, or has cardiac symptoms, baseline electrocardio-graphy or echocardiography, or both, are recommended.

Clinical manifestations of chronic hypertension during pregnancy include⁵:

• in the mother: accelerated hypertension, with resulting target-organ damage involving heart, brain, and kidneys
• in the fetus: placental abruption, preterm birth, fetal growth restriction, and fetal death.

What should treatment seek to accomplish?

The goal of antihypertensive medication during pregnancy is to reduce maternal risk of stroke, congestive heart failure, renal failure, and severe hypertension. No convincing evidence exists that antihypertensive medications decrease the incidence of superimposed preeclampsia, preterm birth, placental abruption, or perinatal death.

According to the American College of Obstetricians and Gynecologists (ACOG), antihypertensive medication is not indicated in patients with uncomplicated chronic hypertension unless systolic BP is ≥ 160 mm Hg or diastolic BP is ≥ 105 mm Hg.³ The goal is to maintain systolic BP at 120–160 mm Hg and diastolic BP at 80–105 mm Hg. The National Institute for Health and Care Excellence recommends treatment of hypertension when systolic BP is ≥ 150 mm Hg or diastolic BP is ≥ 100 mm Hg.⁶ In patients with end-organ disease (chronic renal or cardiac disease) ACOG recommends treatment with an antihypertensive when systolic BP is >140 mm Hg or diastolic BP is >90 mm Hg.

First-line antihypertensives consideredsafe during pregnancy are methyldopa, labetalol, and nifedipine. Thiazide diuretics, although considered second-line agents, may be used during pregnancy—especially if BP is adequately controlled prior to pregnancy. Again, angiotensin-converting enzyme inhibitors and angiotensin-receptor blockers are contraindicated during pregnancy (TABLE 1).³

Continuing care in chronic hypertension

Given the maternal and fetal consequences of chronic hypertension, it is recommended that a hypertensive patient be followed closely as an outpatient; in fact, it is advisablethat she check her BP at least twice daily. Beginning at 24 weeks of gestation, serial ultrasonography should be performed every 4 to 6 weeks to evaluate interval fetal growth. Twice-weekly antepartum testing should begin at 32 to 34 weeks of gestation.

During the course of the pregnancy, the chronically hypertensive patient should be observed closely for development of superimposed preeclampsia. If she does not develop preeclampsia or fetal growth restriction, and has no other pregnancy complications that necessitate early delivery, 3 recommendations regarding timing of delivery apply⁷:

• If the patient is not taking antihypertensive medication, delivery should occur at 38 to 39 6/7 weeks of gestation
• If hypertension is controlled with medication, delivery is recommended at 37 to 39 6/7 weeks of gestation.
• If the patient has severe hypertension that is difficult to control, delivery might be advisable as early as 36 weeks of gestation.

Be vigilant for maternal complications (including cardiac compromise, congestive heart failure, cerebrovascular accident, hypertensive encephalopathy, and worsening renal disease) and fetal complications (such as placental abruption, fetal growth restriction, and fetal death). If any of these occur, management must be tailored and individualized accordingly. Study results have demonstrated that superimposed preeclampsia occurs in 20% to 30% of patients who have underlying mild chronic hypertension. This increases to 50% in women with underlying severe hypertension.⁸

The complex challenge of managing preeclampsia

Chronic hypertension is not the only risk factor for preeclampsia; others include nulliparity, history of preeclampsia, multifetal gestation, underlying renal disease, SLE, antiphospolipid syndrome, thyroid disease, and pregestational diabetes. Furthermore, preeclampsia has a bimodal age distribution, occurring more often in adolescent pregnancies and women of advanced maternal age. Risk is also increased in the presence of abnormal levels of various serum analytes or biochemical markers, such as a low level of pregnancy-associated plasma protein A or estriol or an elevated level of maternal serum α-fetoprotein, human chorionic gonadotropin, or inhibin—findings that might reflect abnormal placentation.⁹

In fact, the findings of most studies that have looked at the pathophysiology of preeclampsia appear to show that several noteworthy pathophysiologic changes are evident in early pregnancy^10,11:

• incomplete trophoblastic invasion of spiral arteries
• retention of thick-walled, muscular arteries
• decreased placental perfusion
• early placental hypoxia
• placental release of factors that lead to endothelial dysfunction and endothelial damage.

Ultimately, vasoconstriction becomes evident, which leads to clinical manifestations of the disorder. In addition, there is an increase in the level of thromboxane (a vasoconstrictor and platelet aggregator), compared to the level of prostacyclin (a vasodilator).

ACOG revises nomenclature, provides recommendations

The considerable expansion of knowledge about preeclampsia over the past 10 to 15 years has not translated to better outcomes. In 2012, ACOG, in response to troubling observations about the condition (see “ACOG finds compelling motivation to boost understanding, management of preeclampsia,”), created a Task Force to investigate hypertension in pregnancy.

Findings and recommendations of the Task Force were published in November 2013,³ and have been endorsed and supported by professional organizations, including the American Academy of Neurology, American Society of Hypertension, Preeclampsia Foundation, and the Society for Maternal-Fetal Medicine. A major premise of the Task Force that has had a direct impact on recommendations for management of preeclampsia is that the condition is a progressive and dynamic process that involves multiple organ systems and is not specifically confined to the antepartum period.

The nomenclature of mild preeclampsia and severe preeclampsia was changed in the Task Force report to preeclampsia without severe features and preeclampsia with severe features. Preeclampsia without severe features is diagnosed when a patient has:

• systolic BP ≥ 140 mm Hg or diastolic BP ≥ 90 mm Hg (measured twice at least 4 hours apart)
• proteinuria, defined as a 24-hour urine collection of ≥ 300 mg of protein or a urine protein–creatinine ratio of  0.3. 

If a patient has elevated BP by those criteria, plus any of several laboratory indicators of multisystem involvement (platelet count, <100 × 10³/μL; serum creatinine level, >1.1 mg/dL; doubling in the serum creatinine concentration; liver transaminase concentrations twice normal) or other findings (pulmonary edema, visual disturbance, headaches), she has preeclampsia with severe features. A diagnosis of preeclampsia without severe features is upgraded to preeclampsia with severe features if systolic BP increases to >160 mm Hgor diastolic BP increases to >110 mm Hg (determined by 2 measurements 4 hours apart) or if “severe”-range BP occurs with such rapidity that acute antihypertensive medication is required.

Pharmacotherapy for hypertensive emergency

Acute BP control with intravenous (IV) labetalol or hydralazine or oral nifedipine is recommended when a patient has a hypertensive emergency, defined as acute-onset severe hypertension that persists for ≥ 15 minutes (TABLE 2).¹² The goal of management is not to completely normalize BP but to lower BP to the range of 140 to 155 mm Hg (systolic) and 90 to 105 mm Hg (diastolic). Of all proposed interventions, these agents are likely the most effective in preventing a maternal cerebrovascular or cardiovascular event. (Note: Labetalol is contraindicated in patients with severe asthma and in the setting of acute cocaine or methamphetamine intoxication. Hydralazine can cause tachycardia.)^13,14

Once a diagnosis of preeclampsia with severe features or superimposed preeclampsia with severe features is made, the patient should remain hospitalized until delivery. If either of these diagnoses is made at ≥ 34 weeks of gestation, there is no reason to prolong pregnancy. Rather, the patient should be given prophylactic magnesium sulfate to prevent seizures and delivery should be accomplished.^15,16 Earlier than 36 6/7 weeks of gestation, consider a late preterm course of corticosteroids; however, do not delay delivery in this situation.¹⁷

Planning for delivery

Route of delivery depends on customary obstetric indications. Before 34 weeks of gestation, corticosteroids, magnesium sulfate, and prolonging the pregnancy until 34 weeks of gestation are recommended. If, at any time, maternal or fetal condition deteriorates, delivery should be accomplished regardless of gestational age. If the patient is unwilling to accept the risks of expectant management of preeclampsia with severe features remote from term, delivery is indicated.^18,19 If delivery is not likely to occur, magnesium sulfate can be discontinued after the patient has received a second dose of corticosteroids, with the plan to resume magnesium sulfate if she develops signs of worsening preeclampsia or eclampsia, or once the plan for delivery is made.

In patients who have either gestational hypertension or preeclampsia without severe features, the recommendation is to accomplish delivery no later than 37 weeks of gestation. While the patient is being expectantly managed, close maternal and fetal surveillance are necessary, comprising serial assessment of maternal symptoms and fetal movement; serial BP measurement (twice weekly); and weekly measurement of the platelet count, serum creatinine, and liver enzymes. At 34 weeks of gestation, conventional antepartum testing should begin. Again, if there is deterioration of the maternal or fetal condition, the patient should be hospitalized and delivery should be accomplished according to the recommendations above.³

Seizure management

If a patient has a tonic–clonic seizure consistent with eclampsia, management should be as follows:

1. Preserve the airway and immediately tilt the head forward to prevent aspiration.
2. If the patient is not receiving magnesium sulfate, immediately administer a loading dose of 4-6 g IV or 10 mg intramuscularly if IV access has not been established.20
3. If the patient is already receiving magnesium sulfate, administer a loading dose of 2 g IV over 5 minutes.
4. If the patient continues to have seizure activity, administer anticonvulsant medication(lorazepam, diazepam, midazolam, or phenytoin).

Eclamptic seizures are usually self-limited, lasting no longer than 1 or 2 minutes. Regrettably, these seizures are unpredictable and contribute significantly to maternal morbidity and mortality.^21,22 A maternal seizure causes a significant interruption in the oxygen pathway to the fetus, with resultant late decelerations, prolonged decelerations, or bradycardia.

Resist the temptation to perform emergent cesarean delivery when eclamptic seizure occurs; rather, allow time for fetal recovery and then proceed with delivery in a controlled fashion. In many circumstances, the patient can undergo vaginal delivery after an eclamptic seizure. Keep in mind that the differential diagnosis of new-onset seizure in pregnancy includes cerebral pathology, such as a bleeding arteriovenous malformation or ruptured aneurysm. Therefore, brain-imaging studies might be indicated, especially in patients who have focal neurologic deficits, or who have seizures either while receiving magnesium sulfate or 48 to 72 hours after delivery.

Preeclampsia postpartum

More recent studies have demonstrated that preeclampsia can be exacerbated after delivery or might even present initially postpartum.^23,24 In all women in whom gestational hypertension, preeclampsia, or superimposed preeclampsia is diagnosed, therefore, recommendations are that BP be monitored in the hospital or on an outpatient basis for at least 72 hours postpartum and again 7 to 10 days after delivery. For all women postpartum, the recommendation is that discharge instructions 1) include information about signs and symptoms of preeclampsia and 2) emphasize the importance of promptly reporting such developments to providers.²⁵ Remember: Sequelae of preeclampsia have been reported as late as 4 to 6 weeks postpartum.

Magnesium sulfate is recommended when a patient presents postpartum with new-onset hypertension associated with headache or blurred vision, or with preeclampsia with severe hypertension. Because nonsteroidal anti-inflammatory drugs can be associated with elevated BP, these medications should be replaced by other analgesics in women with hypertension that persists for more than 1 day postpartum.

Prevention of preeclampsia

Given the significant maternal, fetal, and neonatal complications associated with preeclampsia, a number of studies have sought to determine ways in which this condition can be prevented. Currently, although no interventions appear to prevent preeclampsia in all patients, significant strides have been made in prevention for high-risk patients. Specifically, beginning low-dosage aspirin (most commonly, 81 mg/d, beginning at less than 16 weeks of gestation) has been shown to mitigate—although not eliminate—risk in patients with a history of preeclampsia and those who have chronic hypertension, multifetal gestation, pregestational diabetes, renal disease, SLE, or antiphospholipid syndrome.^26,27Aspirin appears to act by preferentially blocking production of thromboxane, thus reducing the vasoconstrictive properties of this hormone.

Summing up

Hypertensive disorders during pregnancy are associated with significant morbidity and mortality for mother, fetus, and newborn. Preeclampsia, specifically, is recognized as a dynamic and progressive disease that has the potential to involve multiple organ systems, might present for the first time after delivery, and might be associated with long-term risk of hypertension, heart disease, stroke, and venous thromboembolism.^28,29

Share your thoughts! Send your Letter to the Editor to rbarbieri@mdedge.com. Please include your name and the city and state in which you practice.

CASE Onset of nausea and headache, and elevated BP, at full term

A 24-year-old woman (G1P0) at 39 2/7 weeks of gestation without significant medical history and with uncomplicated prenatal care presents to labor and delivery reporting uterine contractions. She reports nausea and vomiting, and reports having a severe headache this morning. Blood pressure (BP) is 154/98 mm Hg. Urine dipstick analysis demonstrates absence of protein.

How should this patient be managed?

Although we have gained a greater understanding of hypertensive disorders in pregnancy—most notably, preeclampsia—during the past 15 years, management of these patients can, as evidenced in the case above, be complicated. Providers must respect this disease and be cognizant of the significant maternal, fetal, and neonatal complications that can be associated with hypertension during pregnancy—a leading cause of preterm birth and maternal mortality in the United States.^1-3 Initiation of early and aggressive antihypertensive medical therapy, when indicated, plays a key role in preventing catastrophic complications of this disease.

Terminology and classification

Hypertension of pregnancy is classified as:

• chronic hypertension: BP≥140/90 mm Hg prior to pregnancy or prior to 20 weeks of gestation. Patients who have persistently elevated BP 12 weeks after delivery are also in this category.
• preeclampsia–eclampsia: hypertension along with multisystem involvement that occurs after 20 weeks of gestation.
• gestational hypertension: hypertension alone after 20 weeks of gestation; in approximately 15% to 25% of these patients, a diagnosis of preeclampsia will be made as pregnancy progresses.
• chronic hypertension with superimposed preeclampsia: hypertension complicated by development of multisystem involvement during the course of the pregnancy—often a challenging diagnosis, associated with greater perinatal morbidity than either chronic hypertension or preeclampsia alone.

Evaluation of the hypertensive gravida

Although most pregnant patients (approximately 90%) who have a diagnosis of chronic hypertension have primary or essential hypertension, a secondary cause—including thyroid disease, systemic lupus erythematosus (SLE), and underlying renal disease—might be present and should be sought out. It is important, therefore, to obtain a comprehensive history along with a directed physical examination and appropriate laboratory tests.

Ideally, a patient with chronic hypertension should be evaluated prior to pregnancy, but this rarely occurs. At the initial encounter, the patient should be informed of risks associated with chronic hypertension, as well as receive education on the signs and symptoms of preeclampsia. Obtain a thorough history—not only to evaluate for secondary causes of hypertension or end-organ involvement (eg, kidney disease), but to identify comorbidities (such as pregestational diabetes mellitus). The patient should be instructed to immediately discontinue any teratogenic medication (such as an angiotensin-converting enzyme inhibitor or angiotensin-receptor blocker).

Routine laboratory evaluation

Testing should comprise a chemistry panel to evaluate serum creatinine, electrolytes, and liver enzymes. A 24-hour urine collection for protein excretion and creatinine clearance or a urine protein–creatinine ratio should be obtained to record baseline kidney function.⁴ (Such testing is important, given that new-onset or worsening proteinuria is a manifestation of superimposed preeclampsia.) All pregnant patients with chronic hypertension also should have a complete blood count, including a platelet count, and an early screen for gestational diabetes.

Depending on what information is obtained from the history and physical examination, renal ultrasonography and any of several laboratory tests can be ordered, including thyroid function, an SLE panel, and vanillylmandelic acid/metanephrines. If the patient has a history of severe hypertension for greater than 5 years, is older than 40 years, or has cardiac symptoms, baseline electrocardio-graphy or echocardiography, or both, are recommended.

Clinical manifestations of chronic hypertension during pregnancy include⁵:

• in the mother: accelerated hypertension, with resulting target-organ damage involving heart, brain, and kidneys
• in the fetus: placental abruption, preterm birth, fetal growth restriction, and fetal death.

What should treatment seek to accomplish?

The goal of antihypertensive medication during pregnancy is to reduce maternal risk of stroke, congestive heart failure, renal failure, and severe hypertension. No convincing evidence exists that antihypertensive medications decrease the incidence of superimposed preeclampsia, preterm birth, placental abruption, or perinatal death.

According to the American College of Obstetricians and Gynecologists (ACOG), antihypertensive medication is not indicated in patients with uncomplicated chronic hypertension unless systolic BP is ≥ 160 mm Hg or diastolic BP is ≥ 105 mm Hg.³ The goal is to maintain systolic BP at 120–160 mm Hg and diastolic BP at 80–105 mm Hg. The National Institute for Health and Care Excellence recommends treatment of hypertension when systolic BP is ≥ 150 mm Hg or diastolic BP is ≥ 100 mm Hg.⁶ In patients with end-organ disease (chronic renal or cardiac disease) ACOG recommends treatment with an antihypertensive when systolic BP is >140 mm Hg or diastolic BP is >90 mm Hg.

First-line antihypertensives consideredsafe during pregnancy are methyldopa, labetalol, and nifedipine. Thiazide diuretics, although considered second-line agents, may be used during pregnancy—especially if BP is adequately controlled prior to pregnancy. Again, angiotensin-converting enzyme inhibitors and angiotensin-receptor blockers are contraindicated during pregnancy (TABLE 1).³

Continuing care in chronic hypertension

Given the maternal and fetal consequences of chronic hypertension, it is recommended that a hypertensive patient be followed closely as an outpatient; in fact, it is advisablethat she check her BP at least twice daily. Beginning at 24 weeks of gestation, serial ultrasonography should be performed every 4 to 6 weeks to evaluate interval fetal growth. Twice-weekly antepartum testing should begin at 32 to 34 weeks of gestation.

During the course of the pregnancy, the chronically hypertensive patient should be observed closely for development of superimposed preeclampsia. If she does not develop preeclampsia or fetal growth restriction, and has no other pregnancy complications that necessitate early delivery, 3 recommendations regarding timing of delivery apply⁷:

• If the patient is not taking antihypertensive medication, delivery should occur at 38 to 39 6/7 weeks of gestation
• If hypertension is controlled with medication, delivery is recommended at 37 to 39 6/7 weeks of gestation.
• If the patient has severe hypertension that is difficult to control, delivery might be advisable as early as 36 weeks of gestation.

Be vigilant for maternal complications (including cardiac compromise, congestive heart failure, cerebrovascular accident, hypertensive encephalopathy, and worsening renal disease) and fetal complications (such as placental abruption, fetal growth restriction, and fetal death). If any of these occur, management must be tailored and individualized accordingly. Study results have demonstrated that superimposed preeclampsia occurs in 20% to 30% of patients who have underlying mild chronic hypertension. This increases to 50% in women with underlying severe hypertension.⁸

The complex challenge of managing preeclampsia

Chronic hypertension is not the only risk factor for preeclampsia; others include nulliparity, history of preeclampsia, multifetal gestation, underlying renal disease, SLE, antiphospolipid syndrome, thyroid disease, and pregestational diabetes. Furthermore, preeclampsia has a bimodal age distribution, occurring more often in adolescent pregnancies and women of advanced maternal age. Risk is also increased in the presence of abnormal levels of various serum analytes or biochemical markers, such as a low level of pregnancy-associated plasma protein A or estriol or an elevated level of maternal serum α-fetoprotein, human chorionic gonadotropin, or inhibin—findings that might reflect abnormal placentation.⁹

In fact, the findings of most studies that have looked at the pathophysiology of preeclampsia appear to show that several noteworthy pathophysiologic changes are evident in early pregnancy^10,11:

• incomplete trophoblastic invasion of spiral arteries
• retention of thick-walled, muscular arteries
• decreased placental perfusion
• early placental hypoxia
• placental release of factors that lead to endothelial dysfunction and endothelial damage.

Ultimately, vasoconstriction becomes evident, which leads to clinical manifestations of the disorder. In addition, there is an increase in the level of thromboxane (a vasoconstrictor and platelet aggregator), compared to the level of prostacyclin (a vasodilator).

ACOG revises nomenclature, provides recommendations

The considerable expansion of knowledge about preeclampsia over the past 10 to 15 years has not translated to better outcomes. In 2012, ACOG, in response to troubling observations about the condition (see “ACOG finds compelling motivation to boost understanding, management of preeclampsia,”), created a Task Force to investigate hypertension in pregnancy.

Findings and recommendations of the Task Force were published in November 2013,³ and have been endorsed and supported by professional organizations, including the American Academy of Neurology, American Society of Hypertension, Preeclampsia Foundation, and the Society for Maternal-Fetal Medicine. A major premise of the Task Force that has had a direct impact on recommendations for management of preeclampsia is that the condition is a progressive and dynamic process that involves multiple organ systems and is not specifically confined to the antepartum period.

The nomenclature of mild preeclampsia and severe preeclampsia was changed in the Task Force report to preeclampsia without severe features and preeclampsia with severe features. Preeclampsia without severe features is diagnosed when a patient has:

• systolic BP ≥ 140 mm Hg or diastolic BP ≥ 90 mm Hg (measured twice at least 4 hours apart)
• proteinuria, defined as a 24-hour urine collection of ≥ 300 mg of protein or a urine protein–creatinine ratio of  0.3. 

If a patient has elevated BP by those criteria, plus any of several laboratory indicators of multisystem involvement (platelet count, <100 × 10³/μL; serum creatinine level, >1.1 mg/dL; doubling in the serum creatinine concentration; liver transaminase concentrations twice normal) or other findings (pulmonary edema, visual disturbance, headaches), she has preeclampsia with severe features. A diagnosis of preeclampsia without severe features is upgraded to preeclampsia with severe features if systolic BP increases to >160 mm Hgor diastolic BP increases to >110 mm Hg (determined by 2 measurements 4 hours apart) or if “severe”-range BP occurs with such rapidity that acute antihypertensive medication is required.

Pharmacotherapy for hypertensive emergency

Acute BP control with intravenous (IV) labetalol or hydralazine or oral nifedipine is recommended when a patient has a hypertensive emergency, defined as acute-onset severe hypertension that persists for ≥ 15 minutes (TABLE 2).¹² The goal of management is not to completely normalize BP but to lower BP to the range of 140 to 155 mm Hg (systolic) and 90 to 105 mm Hg (diastolic). Of all proposed interventions, these agents are likely the most effective in preventing a maternal cerebrovascular or cardiovascular event. (Note: Labetalol is contraindicated in patients with severe asthma and in the setting of acute cocaine or methamphetamine intoxication. Hydralazine can cause tachycardia.)^13,14

Once a diagnosis of preeclampsia with severe features or superimposed preeclampsia with severe features is made, the patient should remain hospitalized until delivery. If either of these diagnoses is made at ≥ 34 weeks of gestation, there is no reason to prolong pregnancy. Rather, the patient should be given prophylactic magnesium sulfate to prevent seizures and delivery should be accomplished.^15,16 Earlier than 36 6/7 weeks of gestation, consider a late preterm course of corticosteroids; however, do not delay delivery in this situation.¹⁷

Planning for delivery

Route of delivery depends on customary obstetric indications. Before 34 weeks of gestation, corticosteroids, magnesium sulfate, and prolonging the pregnancy until 34 weeks of gestation are recommended. If, at any time, maternal or fetal condition deteriorates, delivery should be accomplished regardless of gestational age. If the patient is unwilling to accept the risks of expectant management of preeclampsia with severe features remote from term, delivery is indicated.^18,19 If delivery is not likely to occur, magnesium sulfate can be discontinued after the patient has received a second dose of corticosteroids, with the plan to resume magnesium sulfate if she develops signs of worsening preeclampsia or eclampsia, or once the plan for delivery is made.

In patients who have either gestational hypertension or preeclampsia without severe features, the recommendation is to accomplish delivery no later than 37 weeks of gestation. While the patient is being expectantly managed, close maternal and fetal surveillance are necessary, comprising serial assessment of maternal symptoms and fetal movement; serial BP measurement (twice weekly); and weekly measurement of the platelet count, serum creatinine, and liver enzymes. At 34 weeks of gestation, conventional antepartum testing should begin. Again, if there is deterioration of the maternal or fetal condition, the patient should be hospitalized and delivery should be accomplished according to the recommendations above.³

Seizure management

If a patient has a tonic–clonic seizure consistent with eclampsia, management should be as follows:

1. Preserve the airway and immediately tilt the head forward to prevent aspiration.
2. If the patient is not receiving magnesium sulfate, immediately administer a loading dose of 4-6 g IV or 10 mg intramuscularly if IV access has not been established.20
3. If the patient is already receiving magnesium sulfate, administer a loading dose of 2 g IV over 5 minutes.
4. If the patient continues to have seizure activity, administer anticonvulsant medication(lorazepam, diazepam, midazolam, or phenytoin).

Eclamptic seizures are usually self-limited, lasting no longer than 1 or 2 minutes. Regrettably, these seizures are unpredictable and contribute significantly to maternal morbidity and mortality.^21,22 A maternal seizure causes a significant interruption in the oxygen pathway to the fetus, with resultant late decelerations, prolonged decelerations, or bradycardia.

Resist the temptation to perform emergent cesarean delivery when eclamptic seizure occurs; rather, allow time for fetal recovery and then proceed with delivery in a controlled fashion. In many circumstances, the patient can undergo vaginal delivery after an eclamptic seizure. Keep in mind that the differential diagnosis of new-onset seizure in pregnancy includes cerebral pathology, such as a bleeding arteriovenous malformation or ruptured aneurysm. Therefore, brain-imaging studies might be indicated, especially in patients who have focal neurologic deficits, or who have seizures either while receiving magnesium sulfate or 48 to 72 hours after delivery.

Preeclampsia postpartum

More recent studies have demonstrated that preeclampsia can be exacerbated after delivery or might even present initially postpartum.^23,24 In all women in whom gestational hypertension, preeclampsia, or superimposed preeclampsia is diagnosed, therefore, recommendations are that BP be monitored in the hospital or on an outpatient basis for at least 72 hours postpartum and again 7 to 10 days after delivery. For all women postpartum, the recommendation is that discharge instructions 1) include information about signs and symptoms of preeclampsia and 2) emphasize the importance of promptly reporting such developments to providers.²⁵ Remember: Sequelae of preeclampsia have been reported as late as 4 to 6 weeks postpartum.

Magnesium sulfate is recommended when a patient presents postpartum with new-onset hypertension associated with headache or blurred vision, or with preeclampsia with severe hypertension. Because nonsteroidal anti-inflammatory drugs can be associated with elevated BP, these medications should be replaced by other analgesics in women with hypertension that persists for more than 1 day postpartum.

Prevention of preeclampsia

Given the significant maternal, fetal, and neonatal complications associated with preeclampsia, a number of studies have sought to determine ways in which this condition can be prevented. Currently, although no interventions appear to prevent preeclampsia in all patients, significant strides have been made in prevention for high-risk patients. Specifically, beginning low-dosage aspirin (most commonly, 81 mg/d, beginning at less than 16 weeks of gestation) has been shown to mitigate—although not eliminate—risk in patients with a history of preeclampsia and those who have chronic hypertension, multifetal gestation, pregestational diabetes, renal disease, SLE, or antiphospholipid syndrome.^26,27Aspirin appears to act by preferentially blocking production of thromboxane, thus reducing the vasoconstrictive properties of this hormone.

Summing up

Hypertensive disorders during pregnancy are associated with significant morbidity and mortality for mother, fetus, and newborn. Preeclampsia, specifically, is recognized as a dynamic and progressive disease that has the potential to involve multiple organ systems, might present for the first time after delivery, and might be associated with long-term risk of hypertension, heart disease, stroke, and venous thromboembolism.^28,29

Share your thoughts! Send your Letter to the Editor to rbarbieri@mdedge.com. Please include your name and the city and state in which you practice.

CASE Onset of nausea and headache, and elevated BP, at full term

A 24-year-old woman (G1P0) at 39 2/7 weeks of gestation without significant medical history and with uncomplicated prenatal care presents to labor and delivery reporting uterine contractions. She reports nausea and vomiting, and reports having a severe headache this morning. Blood pressure (BP) is 154/98 mm Hg. Urine dipstick analysis demonstrates absence of protein.

How should this patient be managed?

Although we have gained a greater understanding of hypertensive disorders in pregnancy—most notably, preeclampsia—during the past 15 years, management of these patients can, as evidenced in the case above, be complicated. Providers must respect this disease and be cognizant of the significant maternal, fetal, and neonatal complications that can be associated with hypertension during pregnancy—a leading cause of preterm birth and maternal mortality in the United States.^1-3 Initiation of early and aggressive antihypertensive medical therapy, when indicated, plays a key role in preventing catastrophic complications of this disease.

Terminology and classification

Hypertension of pregnancy is classified as:

• chronic hypertension: BP≥140/90 mm Hg prior to pregnancy or prior to 20 weeks of gestation. Patients who have persistently elevated BP 12 weeks after delivery are also in this category.
• preeclampsia–eclampsia: hypertension along with multisystem involvement that occurs after 20 weeks of gestation.
• gestational hypertension: hypertension alone after 20 weeks of gestation; in approximately 15% to 25% of these patients, a diagnosis of preeclampsia will be made as pregnancy progresses.
• chronic hypertension with superimposed preeclampsia: hypertension complicated by development of multisystem involvement during the course of the pregnancy—often a challenging diagnosis, associated with greater perinatal morbidity than either chronic hypertension or preeclampsia alone.

Evaluation of the hypertensive gravida

Although most pregnant patients (approximately 90%) who have a diagnosis of chronic hypertension have primary or essential hypertension, a secondary cause—including thyroid disease, systemic lupus erythematosus (SLE), and underlying renal disease—might be present and should be sought out. It is important, therefore, to obtain a comprehensive history along with a directed physical examination and appropriate laboratory tests.

Ideally, a patient with chronic hypertension should be evaluated prior to pregnancy, but this rarely occurs. At the initial encounter, the patient should be informed of risks associated with chronic hypertension, as well as receive education on the signs and symptoms of preeclampsia. Obtain a thorough history—not only to evaluate for secondary causes of hypertension or end-organ involvement (eg, kidney disease), but to identify comorbidities (such as pregestational diabetes mellitus). The patient should be instructed to immediately discontinue any teratogenic medication (such as an angiotensin-converting enzyme inhibitor or angiotensin-receptor blocker).

Routine laboratory evaluation

Testing should comprise a chemistry panel to evaluate serum creatinine, electrolytes, and liver enzymes. A 24-hour urine collection for protein excretion and creatinine clearance or a urine protein–creatinine ratio should be obtained to record baseline kidney function.⁴ (Such testing is important, given that new-onset or worsening proteinuria is a manifestation of superimposed preeclampsia.) All pregnant patients with chronic hypertension also should have a complete blood count, including a platelet count, and an early screen for gestational diabetes.

Depending on what information is obtained from the history and physical examination, renal ultrasonography and any of several laboratory tests can be ordered, including thyroid function, an SLE panel, and vanillylmandelic acid/metanephrines. If the patient has a history of severe hypertension for greater than 5 years, is older than 40 years, or has cardiac symptoms, baseline electrocardio-graphy or echocardiography, or both, are recommended.

Clinical manifestations of chronic hypertension during pregnancy include⁵:

• in the mother: accelerated hypertension, with resulting target-organ damage involving heart, brain, and kidneys
• in the fetus: placental abruption, preterm birth, fetal growth restriction, and fetal death.

What should treatment seek to accomplish?

The goal of antihypertensive medication during pregnancy is to reduce maternal risk of stroke, congestive heart failure, renal failure, and severe hypertension. No convincing evidence exists that antihypertensive medications decrease the incidence of superimposed preeclampsia, preterm birth, placental abruption, or perinatal death.

According to the American College of Obstetricians and Gynecologists (ACOG), antihypertensive medication is not indicated in patients with uncomplicated chronic hypertension unless systolic BP is ≥ 160 mm Hg or diastolic BP is ≥ 105 mm Hg.³ The goal is to maintain systolic BP at 120–160 mm Hg and diastolic BP at 80–105 mm Hg. The National Institute for Health and Care Excellence recommends treatment of hypertension when systolic BP is ≥ 150 mm Hg or diastolic BP is ≥ 100 mm Hg.⁶ In patients with end-organ disease (chronic renal or cardiac disease) ACOG recommends treatment with an antihypertensive when systolic BP is >140 mm Hg or diastolic BP is >90 mm Hg.

First-line antihypertensives consideredsafe during pregnancy are methyldopa, labetalol, and nifedipine. Thiazide diuretics, although considered second-line agents, may be used during pregnancy—especially if BP is adequately controlled prior to pregnancy. Again, angiotensin-converting enzyme inhibitors and angiotensin-receptor blockers are contraindicated during pregnancy (TABLE 1).³

Continuing care in chronic hypertension

Given the maternal and fetal consequences of chronic hypertension, it is recommended that a hypertensive patient be followed closely as an outpatient; in fact, it is advisablethat she check her BP at least twice daily. Beginning at 24 weeks of gestation, serial ultrasonography should be performed every 4 to 6 weeks to evaluate interval fetal growth. Twice-weekly antepartum testing should begin at 32 to 34 weeks of gestation.

During the course of the pregnancy, the chronically hypertensive patient should be observed closely for development of superimposed preeclampsia. If she does not develop preeclampsia or fetal growth restriction, and has no other pregnancy complications that necessitate early delivery, 3 recommendations regarding timing of delivery apply⁷:

• If the patient is not taking antihypertensive medication, delivery should occur at 38 to 39 6/7 weeks of gestation
• If hypertension is controlled with medication, delivery is recommended at 37 to 39 6/7 weeks of gestation.
• If the patient has severe hypertension that is difficult to control, delivery might be advisable as early as 36 weeks of gestation.

Be vigilant for maternal complications (including cardiac compromise, congestive heart failure, cerebrovascular accident, hypertensive encephalopathy, and worsening renal disease) and fetal complications (such as placental abruption, fetal growth restriction, and fetal death). If any of these occur, management must be tailored and individualized accordingly. Study results have demonstrated that superimposed preeclampsia occurs in 20% to 30% of patients who have underlying mild chronic hypertension. This increases to 50% in women with underlying severe hypertension.⁸

The complex challenge of managing preeclampsia

Chronic hypertension is not the only risk factor for preeclampsia; others include nulliparity, history of preeclampsia, multifetal gestation, underlying renal disease, SLE, antiphospolipid syndrome, thyroid disease, and pregestational diabetes. Furthermore, preeclampsia has a bimodal age distribution, occurring more often in adolescent pregnancies and women of advanced maternal age. Risk is also increased in the presence of abnormal levels of various serum analytes or biochemical markers, such as a low level of pregnancy-associated plasma protein A or estriol or an elevated level of maternal serum α-fetoprotein, human chorionic gonadotropin, or inhibin—findings that might reflect abnormal placentation.⁹

In fact, the findings of most studies that have looked at the pathophysiology of preeclampsia appear to show that several noteworthy pathophysiologic changes are evident in early pregnancy^10,11:

• incomplete trophoblastic invasion of spiral arteries
• retention of thick-walled, muscular arteries
• decreased placental perfusion
• early placental hypoxia
• placental release of factors that lead to endothelial dysfunction and endothelial damage.

Ultimately, vasoconstriction becomes evident, which leads to clinical manifestations of the disorder. In addition, there is an increase in the level of thromboxane (a vasoconstrictor and platelet aggregator), compared to the level of prostacyclin (a vasodilator).

ACOG revises nomenclature, provides recommendations

The considerable expansion of knowledge about preeclampsia over the past 10 to 15 years has not translated to better outcomes. In 2012, ACOG, in response to troubling observations about the condition (see “ACOG finds compelling motivation to boost understanding, management of preeclampsia,”), created a Task Force to investigate hypertension in pregnancy.

Findings and recommendations of the Task Force were published in November 2013,³ and have been endorsed and supported by professional organizations, including the American Academy of Neurology, American Society of Hypertension, Preeclampsia Foundation, and the Society for Maternal-Fetal Medicine. A major premise of the Task Force that has had a direct impact on recommendations for management of preeclampsia is that the condition is a progressive and dynamic process that involves multiple organ systems and is not specifically confined to the antepartum period.

The nomenclature of mild preeclampsia and severe preeclampsia was changed in the Task Force report to preeclampsia without severe features and preeclampsia with severe features. Preeclampsia without severe features is diagnosed when a patient has:

• systolic BP ≥ 140 mm Hg or diastolic BP ≥ 90 mm Hg (measured twice at least 4 hours apart)
• proteinuria, defined as a 24-hour urine collection of ≥ 300 mg of protein or a urine protein–creatinine ratio of  0.3. 

If a patient has elevated BP by those criteria, plus any of several laboratory indicators of multisystem involvement (platelet count, <100 × 10³/μL; serum creatinine level, >1.1 mg/dL; doubling in the serum creatinine concentration; liver transaminase concentrations twice normal) or other findings (pulmonary edema, visual disturbance, headaches), she has preeclampsia with severe features. A diagnosis of preeclampsia without severe features is upgraded to preeclampsia with severe features if systolic BP increases to >160 mm Hgor diastolic BP increases to >110 mm Hg (determined by 2 measurements 4 hours apart) or if “severe”-range BP occurs with such rapidity that acute antihypertensive medication is required.

Pharmacotherapy for hypertensive emergency

Acute BP control with intravenous (IV) labetalol or hydralazine or oral nifedipine is recommended when a patient has a hypertensive emergency, defined as acute-onset severe hypertension that persists for ≥ 15 minutes (TABLE 2).¹² The goal of management is not to completely normalize BP but to lower BP to the range of 140 to 155 mm Hg (systolic) and 90 to 105 mm Hg (diastolic). Of all proposed interventions, these agents are likely the most effective in preventing a maternal cerebrovascular or cardiovascular event. (Note: Labetalol is contraindicated in patients with severe asthma and in the setting of acute cocaine or methamphetamine intoxication. Hydralazine can cause tachycardia.)^13,14

Once a diagnosis of preeclampsia with severe features or superimposed preeclampsia with severe features is made, the patient should remain hospitalized until delivery. If either of these diagnoses is made at ≥ 34 weeks of gestation, there is no reason to prolong pregnancy. Rather, the patient should be given prophylactic magnesium sulfate to prevent seizures and delivery should be accomplished.^15,16 Earlier than 36 6/7 weeks of gestation, consider a late preterm course of corticosteroids; however, do not delay delivery in this situation.¹⁷

Planning for delivery

Route of delivery depends on customary obstetric indications. Before 34 weeks of gestation, corticosteroids, magnesium sulfate, and prolonging the pregnancy until 34 weeks of gestation are recommended. If, at any time, maternal or fetal condition deteriorates, delivery should be accomplished regardless of gestational age. If the patient is unwilling to accept the risks of expectant management of preeclampsia with severe features remote from term, delivery is indicated.^18,19 If delivery is not likely to occur, magnesium sulfate can be discontinued after the patient has received a second dose of corticosteroids, with the plan to resume magnesium sulfate if she develops signs of worsening preeclampsia or eclampsia, or once the plan for delivery is made.

In patients who have either gestational hypertension or preeclampsia without severe features, the recommendation is to accomplish delivery no later than 37 weeks of gestation. While the patient is being expectantly managed, close maternal and fetal surveillance are necessary, comprising serial assessment of maternal symptoms and fetal movement; serial BP measurement (twice weekly); and weekly measurement of the platelet count, serum creatinine, and liver enzymes. At 34 weeks of gestation, conventional antepartum testing should begin. Again, if there is deterioration of the maternal or fetal condition, the patient should be hospitalized and delivery should be accomplished according to the recommendations above.³

Seizure management

If a patient has a tonic–clonic seizure consistent with eclampsia, management should be as follows:

1. Preserve the airway and immediately tilt the head forward to prevent aspiration.
2. If the patient is not receiving magnesium sulfate, immediately administer a loading dose of 4-6 g IV or 10 mg intramuscularly if IV access has not been established.20
3. If the patient is already receiving magnesium sulfate, administer a loading dose of 2 g IV over 5 minutes.
4. If the patient continues to have seizure activity, administer anticonvulsant medication(lorazepam, diazepam, midazolam, or phenytoin).

Eclamptic seizures are usually self-limited, lasting no longer than 1 or 2 minutes. Regrettably, these seizures are unpredictable and contribute significantly to maternal morbidity and mortality.^21,22 A maternal seizure causes a significant interruption in the oxygen pathway to the fetus, with resultant late decelerations, prolonged decelerations, or bradycardia.

Resist the temptation to perform emergent cesarean delivery when eclamptic seizure occurs; rather, allow time for fetal recovery and then proceed with delivery in a controlled fashion. In many circumstances, the patient can undergo vaginal delivery after an eclamptic seizure. Keep in mind that the differential diagnosis of new-onset seizure in pregnancy includes cerebral pathology, such as a bleeding arteriovenous malformation or ruptured aneurysm. Therefore, brain-imaging studies might be indicated, especially in patients who have focal neurologic deficits, or who have seizures either while receiving magnesium sulfate or 48 to 72 hours after delivery.

Preeclampsia postpartum

More recent studies have demonstrated that preeclampsia can be exacerbated after delivery or might even present initially postpartum.^23,24 In all women in whom gestational hypertension, preeclampsia, or superimposed preeclampsia is diagnosed, therefore, recommendations are that BP be monitored in the hospital or on an outpatient basis for at least 72 hours postpartum and again 7 to 10 days after delivery. For all women postpartum, the recommendation is that discharge instructions 1) include information about signs and symptoms of preeclampsia and 2) emphasize the importance of promptly reporting such developments to providers.²⁵ Remember: Sequelae of preeclampsia have been reported as late as 4 to 6 weeks postpartum.

Magnesium sulfate is recommended when a patient presents postpartum with new-onset hypertension associated with headache or blurred vision, or with preeclampsia with severe hypertension. Because nonsteroidal anti-inflammatory drugs can be associated with elevated BP, these medications should be replaced by other analgesics in women with hypertension that persists for more than 1 day postpartum.

Prevention of preeclampsia

Given the significant maternal, fetal, and neonatal complications associated with preeclampsia, a number of studies have sought to determine ways in which this condition can be prevented. Currently, although no interventions appear to prevent preeclampsia in all patients, significant strides have been made in prevention for high-risk patients. Specifically, beginning low-dosage aspirin (most commonly, 81 mg/d, beginning at less than 16 weeks of gestation) has been shown to mitigate—although not eliminate—risk in patients with a history of preeclampsia and those who have chronic hypertension, multifetal gestation, pregestational diabetes, renal disease, SLE, or antiphospholipid syndrome.^26,27Aspirin appears to act by preferentially blocking production of thromboxane, thus reducing the vasoconstrictive properties of this hormone.

Summing up

Hypertensive disorders during pregnancy are associated with significant morbidity and mortality for mother, fetus, and newborn. Preeclampsia, specifically, is recognized as a dynamic and progressive disease that has the potential to involve multiple organ systems, might present for the first time after delivery, and might be associated with long-term risk of hypertension, heart disease, stroke, and venous thromboembolism.^28,29

Share your thoughts! Send your Letter to the Editor to rbarbieri@mdedge.com. Please include your name and the city and state in which you practice.

More than 170 physician groups are calling on the Centers for Medicare & Medicaid Services to withdraw a provision in the proposed 2019 physician fee schedule that would flatten evaluation and management payments.

TheaDesign/Thinkstock

The controversial proposal would set the payment rate for a level 1 evaluation and management (E/M) office visit for a new patient at $44, down from the $45 using the current methodology. Payment for levels 2-5 would be $135. Currently, payments for level 2 new patient visits are set at $76, level 3 at $110, level 4 at $167, and level 5 at $211.

For E/M office visits with established patients, the proposed rate would be $24 for level 1, up from the current payment of $22. Payment for levels 2-5 would be $93. Under the current methodology, payments for established patient level 2 visits are set at $45, level 3 at $74, level 4 at $109, and level 5 at $148.

In an Aug. 28 letter to the CMS, led by the American College of Rheumatology, physician groups applauded CMS recognition of the problems with the current E/M documentation guidelines and codes, but urged them to reconsider plans to “cut and consolidate evaluation and management services.” Doing so would “severely reduce Medicare patients’ access to care by cutting payments for complex office visits, adversely effecting the care and treatment of patients with complex conditions, and potentially exacerbate physician workforce shortages.”

A separate letter, led by the American Medical Association, made similar assertions that the current proposal has the potential to “hurt physicians and other health care professionals in specialties that treat the sickest patients, as well as those who provide comprehensive primary care, ultimately jeopardizing patients’ access to care.”

Daniel P. McQuillen, MD, of Lahey Hospital and Medical Center, Burlington, Mass. and member of the Infectious Diseases Society of America, said that IDSA is “worried that the implementation is being pushed ahead too fast without really considering whether it’s the right way of doing it and whether there might be some alternative ways of doing it that make more sense.”

Another concern related to the implementation of this proposal is the financial impact on physicians.

Implementation of the CMS proposal, as currently written, “would be amazingly expensive for private practice [doctors] and really for anyone else because we would have to change our EMRs,” Barbara Levy, MD, cochair of the CPT/RUC Work Group at the AMA.

“We would have to reprogram our billing software. All of that comes with a significant cost,” said Dr. Levy, who also serves as vice president of health policy at the American College of Obstetricians and Gynecologists.

Part of the selling point of the CMS proposal is the reduction in documentation that accompanies the E/M payment changes. The goal, according to the CMS, is to reduce time spent on paperwork and free up physicians to devote more time to patient care. But some physicians are skeptical it would work out that way.

“I don’t think it is going to change my documentation burden very much,” Jeffery Ward, MD, chair of the American Society of Clinical Oncology Government Relations Committee, said in an interview. “Their assumption is that I write my notes in order to meet a billing requirement and if I don’t have that billing requirement, I won’t have to write nearly as detailed notes. My notes are written so that if someone else needs to take care of my patient when I am not there, they can step in, read my notes, know what’s going on, and follow the patient.”

Dr. Ward suggested that the real purpose of the proposal is to shift more money to primary care, and raised the concern that the CMS is using this proposal “as a vehicle to take money away from specialists who take care of very complicated patients in order to give it to other people, particularly to primary care.”

ASCO and the Community Oncology Alliance both anticipate a 7%-8% reduction in payments to cancer specialists if this provision takes effect, Dr. Ward said.

Another element of the proposal that is raising concerns among physician groups is a proposed payment reduction when a visit involves more than one service. For example, when a single office visit includes both an E/M code and a procedure code, the proposal calls for the E/M code to be cut in half.

“From the patients’ perspective, the potential threat is that doctors could be incentivized to spend less time with patients or potentially bring patients back for subsequent visits to handle multiple problems,” Angus Worthing, MD, chair of the American College of Rheumatology’s Committee on Government Affairs, said in an interview.

Comments on the proposed update to the 2019 Medicare physician fee schedule are due Sept. 10.

gtwachtman@mdedge.com

More than 170 physician groups are calling on the Centers for Medicare & Medicaid Services to withdraw a provision in the proposed 2019 physician fee schedule that would flatten evaluation and management payments.

TheaDesign/Thinkstock

The controversial proposal would set the payment rate for a level 1 evaluation and management (E/M) office visit for a new patient at $44, down from the $45 using the current methodology. Payment for levels 2-5 would be $135. Currently, payments for level 2 new patient visits are set at $76, level 3 at $110, level 4 at $167, and level 5 at $211.

For E/M office visits with established patients, the proposed rate would be $24 for level 1, up from the current payment of $22. Payment for levels 2-5 would be $93. Under the current methodology, payments for established patient level 2 visits are set at $45, level 3 at $74, level 4 at $109, and level 5 at $148.

In an Aug. 28 letter to the CMS, led by the American College of Rheumatology, physician groups applauded CMS recognition of the problems with the current E/M documentation guidelines and codes, but urged them to reconsider plans to “cut and consolidate evaluation and management services.” Doing so would “severely reduce Medicare patients’ access to care by cutting payments for complex office visits, adversely effecting the care and treatment of patients with complex conditions, and potentially exacerbate physician workforce shortages.”

A separate letter, led by the American Medical Association, made similar assertions that the current proposal has the potential to “hurt physicians and other health care professionals in specialties that treat the sickest patients, as well as those who provide comprehensive primary care, ultimately jeopardizing patients’ access to care.”

Daniel P. McQuillen, MD, of Lahey Hospital and Medical Center, Burlington, Mass. and member of the Infectious Diseases Society of America, said that IDSA is “worried that the implementation is being pushed ahead too fast without really considering whether it’s the right way of doing it and whether there might be some alternative ways of doing it that make more sense.”

Another concern related to the implementation of this proposal is the financial impact on physicians.

Implementation of the CMS proposal, as currently written, “would be amazingly expensive for private practice [doctors] and really for anyone else because we would have to change our EMRs,” Barbara Levy, MD, cochair of the CPT/RUC Work Group at the AMA.

“We would have to reprogram our billing software. All of that comes with a significant cost,” said Dr. Levy, who also serves as vice president of health policy at the American College of Obstetricians and Gynecologists.

Part of the selling point of the CMS proposal is the reduction in documentation that accompanies the E/M payment changes. The goal, according to the CMS, is to reduce time spent on paperwork and free up physicians to devote more time to patient care. But some physicians are skeptical it would work out that way.

“I don’t think it is going to change my documentation burden very much,” Jeffery Ward, MD, chair of the American Society of Clinical Oncology Government Relations Committee, said in an interview. “Their assumption is that I write my notes in order to meet a billing requirement and if I don’t have that billing requirement, I won’t have to write nearly as detailed notes. My notes are written so that if someone else needs to take care of my patient when I am not there, they can step in, read my notes, know what’s going on, and follow the patient.”

Dr. Ward suggested that the real purpose of the proposal is to shift more money to primary care, and raised the concern that the CMS is using this proposal “as a vehicle to take money away from specialists who take care of very complicated patients in order to give it to other people, particularly to primary care.”

ASCO and the Community Oncology Alliance both anticipate a 7%-8% reduction in payments to cancer specialists if this provision takes effect, Dr. Ward said.

Another element of the proposal that is raising concerns among physician groups is a proposed payment reduction when a visit involves more than one service. For example, when a single office visit includes both an E/M code and a procedure code, the proposal calls for the E/M code to be cut in half.

“From the patients’ perspective, the potential threat is that doctors could be incentivized to spend less time with patients or potentially bring patients back for subsequent visits to handle multiple problems,” Angus Worthing, MD, chair of the American College of Rheumatology’s Committee on Government Affairs, said in an interview.

Comments on the proposed update to the 2019 Medicare physician fee schedule are due Sept. 10.

gtwachtman@mdedge.com

More than 170 physician groups are calling on the Centers for Medicare & Medicaid Services to withdraw a provision in the proposed 2019 physician fee schedule that would flatten evaluation and management payments.

TheaDesign/Thinkstock

The controversial proposal would set the payment rate for a level 1 evaluation and management (E/M) office visit for a new patient at $44, down from the $45 using the current methodology. Payment for levels 2-5 would be $135. Currently, payments for level 2 new patient visits are set at $76, level 3 at $110, level 4 at $167, and level 5 at $211.

For E/M office visits with established patients, the proposed rate would be $24 for level 1, up from the current payment of $22. Payment for levels 2-5 would be $93. Under the current methodology, payments for established patient level 2 visits are set at $45, level 3 at $74, level 4 at $109, and level 5 at $148.

In an Aug. 28 letter to the CMS, led by the American College of Rheumatology, physician groups applauded CMS recognition of the problems with the current E/M documentation guidelines and codes, but urged them to reconsider plans to “cut and consolidate evaluation and management services.” Doing so would “severely reduce Medicare patients’ access to care by cutting payments for complex office visits, adversely effecting the care and treatment of patients with complex conditions, and potentially exacerbate physician workforce shortages.”

A separate letter, led by the American Medical Association, made similar assertions that the current proposal has the potential to “hurt physicians and other health care professionals in specialties that treat the sickest patients, as well as those who provide comprehensive primary care, ultimately jeopardizing patients’ access to care.”

Daniel P. McQuillen, MD, of Lahey Hospital and Medical Center, Burlington, Mass. and member of the Infectious Diseases Society of America, said that IDSA is “worried that the implementation is being pushed ahead too fast without really considering whether it’s the right way of doing it and whether there might be some alternative ways of doing it that make more sense.”

Another concern related to the implementation of this proposal is the financial impact on physicians.

Implementation of the CMS proposal, as currently written, “would be amazingly expensive for private practice [doctors] and really for anyone else because we would have to change our EMRs,” Barbara Levy, MD, cochair of the CPT/RUC Work Group at the AMA.

“We would have to reprogram our billing software. All of that comes with a significant cost,” said Dr. Levy, who also serves as vice president of health policy at the American College of Obstetricians and Gynecologists.

Part of the selling point of the CMS proposal is the reduction in documentation that accompanies the E/M payment changes. The goal, according to the CMS, is to reduce time spent on paperwork and free up physicians to devote more time to patient care. But some physicians are skeptical it would work out that way.

“I don’t think it is going to change my documentation burden very much,” Jeffery Ward, MD, chair of the American Society of Clinical Oncology Government Relations Committee, said in an interview. “Their assumption is that I write my notes in order to meet a billing requirement and if I don’t have that billing requirement, I won’t have to write nearly as detailed notes. My notes are written so that if someone else needs to take care of my patient when I am not there, they can step in, read my notes, know what’s going on, and follow the patient.”

Dr. Ward suggested that the real purpose of the proposal is to shift more money to primary care, and raised the concern that the CMS is using this proposal “as a vehicle to take money away from specialists who take care of very complicated patients in order to give it to other people, particularly to primary care.”

ASCO and the Community Oncology Alliance both anticipate a 7%-8% reduction in payments to cancer specialists if this provision takes effect, Dr. Ward said.

Another element of the proposal that is raising concerns among physician groups is a proposed payment reduction when a visit involves more than one service. For example, when a single office visit includes both an E/M code and a procedure code, the proposal calls for the E/M code to be cut in half.

“From the patients’ perspective, the potential threat is that doctors could be incentivized to spend less time with patients or potentially bring patients back for subsequent visits to handle multiple problems,” Angus Worthing, MD, chair of the American College of Rheumatology’s Committee on Government Affairs, said in an interview.

Comments on the proposed update to the 2019 Medicare physician fee schedule are due Sept. 10.

gtwachtman@mdedge.com

Against the backdrop of a near doubling in the incidence of congenital syphilis in the United States, the U.S. Preventive Services Task Force has reaffirmed its 2009 recommendation to screen all pregnant women for syphilis as early as possible in pregnancy.

The advice was the task force’s primary recommendation, based on a systematic review of seven studies and backed by the highest grade of evidence, in a statement published in JAMA. Untreated syphilis can be transmitted to the fetus at any time during pregnancy or birth, and congenital syphilis is associated with significant neonatal morbidity – including bone deformities and neurologic impairment – as well as stillbirth and neonatal death.

The prevalence of congenital syphilis was in decline from 2008 to 2012, but then increased by 87% from 2012 to 2016 – from 8.4 cases per 100,000 live births in 2012 to 15.7 cases in 2016. The increase coincided with rising national rates of syphilis among women of reproductive age – from 0.9 cases of primary and secondary syphilis infection per 100,000 women in 2012 to 1.9 cases in 2016.

Additionally, the task force recommended that pregnant women who had not received prenatal care be screened at delivery.

“Although nearly 70% of infants with congenital syphilis are born to mothers who received prenatal care, detection, and treatment of maternal syphilis often occurs too late to treat the fetus and prevent congenital syphilis,” wrote Susan J. Curry, PhD, from the University of Iowa, Iowa City, and her coauthors. “Recent data suggest that while screening rates for syphilis infection are generally high, the proportion of women screened earlier in pregnancy remains low (for example, 20% of women are screened only at the time of delivery).”

The review pointed to an observational study of the impact of the introduction of syphilis screening during pregnancy in China. That study of more than 2 million women showed that screening for syphilis in pregnancy increased from 89.8% of women in 2002 to 97.2% of women in 2012 and was associated with a decrease in the incidence of congenital syphilis from 109.3 cases to 9.4 cases per 100,000 live births.

The group found convincing evidence that screening reduced both the incidence of congenital syphilis and the risk of adverse outcomes related to maternal infection and that the potential harms of screening – such as false positives – were small.

The paper also referenced guidelines from the Centers for Disease Control and Prevention, the American Academy of Pediatrics, and the American College of Obstetricians and Gynecologists that high-risk women – such as those living in areas or communities with a higher prevalence of syphilis, women with HIV, or with a history of incarceration or sex work – should also be rescreened early in the third trimester and again at delivery. Similarly, women who are exposed to an infected partner also should be rescreened.

Further, the task force recommended screening for nonpregnant adolescents and adults at increased risk of syphilis infection.

In terms of treatment, the CDC currently recommends parenteral penicillin G benzathine as the treatment of choice for syphilis in pregnant women. However, the task force recommended clinicians consult the CDC website for updates.

The authors noted that no studies that met the inclusion criteria examined whether penicillin use during pregnancy was associated with any harm or looked at serious adverse events in women with a history of penicillin allergy.

“Because the review was primarily focused on screening, it did not address the efficacy of alternative antibiotic treatments [e.g., ceftriaxone] in pregnant women [with or without penicillin allergies],” the authors wrote.

The research was funded by the U.S. Department of Health and Human Services. No conflicts of interest were reported.

SOURCE: Curry S et al. JAMA. 2018;320:911-7.

Against the backdrop of a near doubling in the incidence of congenital syphilis in the United States, the U.S. Preventive Services Task Force has reaffirmed its 2009 recommendation to screen all pregnant women for syphilis as early as possible in pregnancy.

The advice was the task force’s primary recommendation, based on a systematic review of seven studies and backed by the highest grade of evidence, in a statement published in JAMA. Untreated syphilis can be transmitted to the fetus at any time during pregnancy or birth, and congenital syphilis is associated with significant neonatal morbidity – including bone deformities and neurologic impairment – as well as stillbirth and neonatal death.

The prevalence of congenital syphilis was in decline from 2008 to 2012, but then increased by 87% from 2012 to 2016 – from 8.4 cases per 100,000 live births in 2012 to 15.7 cases in 2016. The increase coincided with rising national rates of syphilis among women of reproductive age – from 0.9 cases of primary and secondary syphilis infection per 100,000 women in 2012 to 1.9 cases in 2016.

Additionally, the task force recommended that pregnant women who had not received prenatal care be screened at delivery.

“Although nearly 70% of infants with congenital syphilis are born to mothers who received prenatal care, detection, and treatment of maternal syphilis often occurs too late to treat the fetus and prevent congenital syphilis,” wrote Susan J. Curry, PhD, from the University of Iowa, Iowa City, and her coauthors. “Recent data suggest that while screening rates for syphilis infection are generally high, the proportion of women screened earlier in pregnancy remains low (for example, 20% of women are screened only at the time of delivery).”

The review pointed to an observational study of the impact of the introduction of syphilis screening during pregnancy in China. That study of more than 2 million women showed that screening for syphilis in pregnancy increased from 89.8% of women in 2002 to 97.2% of women in 2012 and was associated with a decrease in the incidence of congenital syphilis from 109.3 cases to 9.4 cases per 100,000 live births.

The group found convincing evidence that screening reduced both the incidence of congenital syphilis and the risk of adverse outcomes related to maternal infection and that the potential harms of screening – such as false positives – were small.

The paper also referenced guidelines from the Centers for Disease Control and Prevention, the American Academy of Pediatrics, and the American College of Obstetricians and Gynecologists that high-risk women – such as those living in areas or communities with a higher prevalence of syphilis, women with HIV, or with a history of incarceration or sex work – should also be rescreened early in the third trimester and again at delivery. Similarly, women who are exposed to an infected partner also should be rescreened.

Further, the task force recommended screening for nonpregnant adolescents and adults at increased risk of syphilis infection.

In terms of treatment, the CDC currently recommends parenteral penicillin G benzathine as the treatment of choice for syphilis in pregnant women. However, the task force recommended clinicians consult the CDC website for updates.

The authors noted that no studies that met the inclusion criteria examined whether penicillin use during pregnancy was associated with any harm or looked at serious adverse events in women with a history of penicillin allergy.

“Because the review was primarily focused on screening, it did not address the efficacy of alternative antibiotic treatments [e.g., ceftriaxone] in pregnant women [with or without penicillin allergies],” the authors wrote.

The research was funded by the U.S. Department of Health and Human Services. No conflicts of interest were reported.

SOURCE: Curry S et al. JAMA. 2018;320:911-7.

Against the backdrop of a near doubling in the incidence of congenital syphilis in the United States, the U.S. Preventive Services Task Force has reaffirmed its 2009 recommendation to screen all pregnant women for syphilis as early as possible in pregnancy.

The advice was the task force’s primary recommendation, based on a systematic review of seven studies and backed by the highest grade of evidence, in a statement published in JAMA. Untreated syphilis can be transmitted to the fetus at any time during pregnancy or birth, and congenital syphilis is associated with significant neonatal morbidity – including bone deformities and neurologic impairment – as well as stillbirth and neonatal death.

The prevalence of congenital syphilis was in decline from 2008 to 2012, but then increased by 87% from 2012 to 2016 – from 8.4 cases per 100,000 live births in 2012 to 15.7 cases in 2016. The increase coincided with rising national rates of syphilis among women of reproductive age – from 0.9 cases of primary and secondary syphilis infection per 100,000 women in 2012 to 1.9 cases in 2016.

Additionally, the task force recommended that pregnant women who had not received prenatal care be screened at delivery.

“Although nearly 70% of infants with congenital syphilis are born to mothers who received prenatal care, detection, and treatment of maternal syphilis often occurs too late to treat the fetus and prevent congenital syphilis,” wrote Susan J. Curry, PhD, from the University of Iowa, Iowa City, and her coauthors. “Recent data suggest that while screening rates for syphilis infection are generally high, the proportion of women screened earlier in pregnancy remains low (for example, 20% of women are screened only at the time of delivery).”

The review pointed to an observational study of the impact of the introduction of syphilis screening during pregnancy in China. That study of more than 2 million women showed that screening for syphilis in pregnancy increased from 89.8% of women in 2002 to 97.2% of women in 2012 and was associated with a decrease in the incidence of congenital syphilis from 109.3 cases to 9.4 cases per 100,000 live births.

The group found convincing evidence that screening reduced both the incidence of congenital syphilis and the risk of adverse outcomes related to maternal infection and that the potential harms of screening – such as false positives – were small.

The paper also referenced guidelines from the Centers for Disease Control and Prevention, the American Academy of Pediatrics, and the American College of Obstetricians and Gynecologists that high-risk women – such as those living in areas or communities with a higher prevalence of syphilis, women with HIV, or with a history of incarceration or sex work – should also be rescreened early in the third trimester and again at delivery. Similarly, women who are exposed to an infected partner also should be rescreened.

Further, the task force recommended screening for nonpregnant adolescents and adults at increased risk of syphilis infection.

In terms of treatment, the CDC currently recommends parenteral penicillin G benzathine as the treatment of choice for syphilis in pregnant women. However, the task force recommended clinicians consult the CDC website for updates.

The authors noted that no studies that met the inclusion criteria examined whether penicillin use during pregnancy was associated with any harm or looked at serious adverse events in women with a history of penicillin allergy.

“Because the review was primarily focused on screening, it did not address the efficacy of alternative antibiotic treatments [e.g., ceftriaxone] in pregnant women [with or without penicillin allergies],” the authors wrote.

The research was funded by the U.S. Department of Health and Human Services. No conflicts of interest were reported.

SOURCE: Curry S et al. JAMA. 2018;320:911-7.

Practicing in the field of obstetrics and gynecology affords us a special privilege: we are part of the most important and unforgettable events in our patients’ lives, both in sickness and in health. Along with the great joys we share comes profound responsibility and the recognition that we are only as effective as the team with whom we work. Although we live in a country that is home to some of the best health care systems in the world, the maternal mortality rates and disease burden among women in underserved communities belie this fact. A University of Washington study demonstrated a more than 20-year gap in life expectancy between wealthy and poor communities in the United States from 1980 to 2014.¹ Not surprisingly, access to medical care was a contributing factor.

Poverty only partly explains this disparity. Racial differences are at play as well. In 1992, a seminal study by Schoendorf and colleagues² demonstrated that the death rates of babies born to educated African American parents were higher due to lower birth weights. Concern recently has been amplified, and many lay publications have publicly raised the alarm.³ Several states have started investigating the causes, and the American College of Obstetrics and Gynecology, as well as other organizations, are studying possible solutions.

With nearly 50% of US births financed by Medicaid,⁵ there was great hope that the Patient Protection and Affordable Care Act and expansion of Medicaid would result in improved access and quality of health care for underserved patients; however, it has become apparent that coverage did not confer improved access to quality care, especially for medical specialties.

Urban and rural poor populations generally seek medical services from safety net clinics staffed by midlevel and physician primary care providers whose tight schedules, documentation demands, and low reimbursement rates are coupled with complex medical and socioeconomic patient populations. While these providers may be skilled in basic primary care, their patients often present with conditions outside their scope of practice. Our country’s growing physician shortage, along with patient location and personal logistics, adds to the challenges for patients and providers alike. And who among us is not asked several times a week, even by our well-insured patients, for a primary care or specialist physician recommendation? The barriers for seeking medical care in rural populations are even greater, as local hospitals and clinics are closing at an alarming rate.

Alumni at work

Communities of physicians across the country recognize both the access problem and the potential to create solutions. Organizations such as Project ECHO, launched in 2003 through the University of New Mexico, connect rural providers with university physicians to aid in treatment of hepatitis C and other illnesses.

As the date for implementation of the Patient Protection and Affordable Care Act approached, a group of medical school alumni leaders recognized that we could come together and offer our services to address growing health care disparities. Galvanized by the challenge, the Medical Alumni Volunteer Expert Network, or MAVEN Project, was, in our parlance, “born.”

While the concept of the MAVEN Project was germinating, we interviewed numerous colleagues for advice and input and were struck by their desire—especially among the newly retired—to continue to give back. Medicine is a calling, not just a job, and for many of us the joy of helping—the exhilaration of that first birth that sold us on our specialty—gives us meaning and purpose. Many physicians who had left full-time clinical medicine missed the collegiality of the “doctors’ lounge.” Throughout our careers, we are part of a cohort: our medical school class, our residency partners, our hospital staff—we all crave community. With 36% of US physicians older than age 55 and 240,000 retired doctors in the country, we realized a motivated, previously untapped workforce could be marshaled to form a community to serve the most vulnerable among us.⁵

At the same time, telemedicine had come into its own. Simple technology could enable us to see each other on smartphones and computers and even perform portions of a physical examination from afar.

We realized we could marry opportunity (the workforce), need (underserved populations across the country), and technology. The Harvard Medical School Center Primary Care supported a feasibility study, and the MAVEN Project began “seeing” patients in 2016.

A model of hope

The MAVEN Project matches physician volunteers with safety net clinics serving patients in need and provides malpractice insurance and a Health Information Portability and Accountability Act–compliant technology platform to facilitate remote communication. Our volunteers mentor and educate primary care providers in the field and offer both immediate and asynchronous advisory consults. Clinic providers can group cases for discussion, ask urgent questions, or receive advice and support for the day-to-day challenges facing clinicians today. Clinics choose educational topics, focusing on tools needed for patient care rather than esoteric mechanisms of disease. Patients receive best-in-class care conveniently and locally, and by making volunteering easy, we build partnerships that augment patient and provider satisfaction, support long-term capacity building, and improve service delivery.

Our volunteer physicians now represent more than 30 medical specialties and 25 medical schools, and we have completed more than 2,000 consultations to date. Our clinics are located in 6 states (California, Florida, Massachusetts, New York, South Dakota, and Washington), and thanks to our model, physician state of licensure is not an impediment to volunteering. Several colleagues in our specialty are providing advice in women’s health.

Driving innovative solutions

Elizabeth Kopin, MD, an ObGyn who practiced for 28 years in Worcester, Massachusetts, and volunteers for the MAVEN Project, eloquently described in correspondence with Project coordinators the spirit that embodies the pursuit of medicine and the organization’s mission. As Dr. Kopin stated, “The driving force behind my entering medicine was to help people in an essential and meaningful way. I was especially driven to participate in the care of women. I wanted to gain knowledge and skills to help women with health care throughout their lives.”

Dr. Kopin’s capacity to care for patients in the clinic and hospital was progressively reduced as her multiple sclerosis advanced. As a result, she retired from clinical practice, but her desire to participate and contribute to medicine with the passion with which she entered it remained.

Her father was an internist who started a charitable clinic in Georgia. Like her father, Dr. Kopin began her medical career in academic medicine. Her father felt that his last 15 years in medicine were the most meaningful of his career because of his work with underserved populations. Dr. Kopin is following in his footsteps. For her, “Looking for a telehealth vehicle helping communities in need gives me the opportunity to use my abilities in the best way possible.” Dr. Kopin also stated, “Helping the underserved was something I wanted to devote my time to and The MAVEN Project has given me that possibility.”

We like to think of ourselves as Match. com meets the Peace Corps, with the goal to reach underserved patients in all 50 states in both rural and urban communities. We ask for as little as 4 hours of your time per month, and all you need is a computer or smartphone and a medical license. We welcome volunteers in active or part-time practice, academics, and industry: your years of wisdom are invaluable.

The vast complexities of the US health care system are by no measure easy to address, but standing by and allowing a fractured system to rupture is not an option. Each of us has an expertise and an opportunity to make incremental steps to ensure that those who need health care do not slip through the cracks. Dr. Kopin and I are fortunate to have a skill to help others and, in the MAVEN Project, a robust, dedicated network of individuals who share our vision.

There are many who have and continue to inspire a guiding conscience to serve beyond oneself. George H.W. Bush said it best when explaining why he founded the Points of Light organization nearly 3 decades ago⁶:

I have pursued life itself over many years now and with varying degrees of happiness. Some of my happiness still comes from trying to be in my own small way a true “point of light.” I believe I was right when I said, as President, there can be no definition of a successful life that does not include service to others. So I do that now, and I gain happiness. I do not seek a Pulitzer Prize. I do not want press attention…. I have found happiness. I no longer pursue it, for it is mine.

Please join us on our mission!

How to join

We are actively seeking specialty and primary care physicians to provide advisory consultations, mentorship, and education via telehealth technology. We welcome physician volunteers who:

• are newly retired, semi-retired, in industry, or in clinical practice
• have a minimum of 2 years of clinical practice experience
• have been active in the medical community in the past 3 years
• have an active or volunteer US medical license (any state)
• are able to provide 3 professional references
• are willing to commit a minimum of 4 hours per month for 6 months.

Visit us online to complete our physician volunteer inquiry form (https://www.mavenproject.org/work-with-us/#wwu-volunteer-as-a-physician-lightblue).

Share your thoughts! Send your Letter to the Editor to rbarbieri@mdedge.com. Please include your name and the city and state in which you practice.

Practicing in the field of obstetrics and gynecology affords us a special privilege: we are part of the most important and unforgettable events in our patients’ lives, both in sickness and in health. Along with the great joys we share comes profound responsibility and the recognition that we are only as effective as the team with whom we work. Although we live in a country that is home to some of the best health care systems in the world, the maternal mortality rates and disease burden among women in underserved communities belie this fact. A University of Washington study demonstrated a more than 20-year gap in life expectancy between wealthy and poor communities in the United States from 1980 to 2014.¹ Not surprisingly, access to medical care was a contributing factor.

Poverty only partly explains this disparity. Racial differences are at play as well. In 1992, a seminal study by Schoendorf and colleagues² demonstrated that the death rates of babies born to educated African American parents were higher due to lower birth weights. Concern recently has been amplified, and many lay publications have publicly raised the alarm.³ Several states have started investigating the causes, and the American College of Obstetrics and Gynecology, as well as other organizations, are studying possible solutions.

With nearly 50% of US births financed by Medicaid,⁵ there was great hope that the Patient Protection and Affordable Care Act and expansion of Medicaid would result in improved access and quality of health care for underserved patients; however, it has become apparent that coverage did not confer improved access to quality care, especially for medical specialties.

Urban and rural poor populations generally seek medical services from safety net clinics staffed by midlevel and physician primary care providers whose tight schedules, documentation demands, and low reimbursement rates are coupled with complex medical and socioeconomic patient populations. While these providers may be skilled in basic primary care, their patients often present with conditions outside their scope of practice. Our country’s growing physician shortage, along with patient location and personal logistics, adds to the challenges for patients and providers alike. And who among us is not asked several times a week, even by our well-insured patients, for a primary care or specialist physician recommendation? The barriers for seeking medical care in rural populations are even greater, as local hospitals and clinics are closing at an alarming rate.

Alumni at work

Communities of physicians across the country recognize both the access problem and the potential to create solutions. Organizations such as Project ECHO, launched in 2003 through the University of New Mexico, connect rural providers with university physicians to aid in treatment of hepatitis C and other illnesses.

As the date for implementation of the Patient Protection and Affordable Care Act approached, a group of medical school alumni leaders recognized that we could come together and offer our services to address growing health care disparities. Galvanized by the challenge, the Medical Alumni Volunteer Expert Network, or MAVEN Project, was, in our parlance, “born.”

While the concept of the MAVEN Project was germinating, we interviewed numerous colleagues for advice and input and were struck by their desire—especially among the newly retired—to continue to give back. Medicine is a calling, not just a job, and for many of us the joy of helping—the exhilaration of that first birth that sold us on our specialty—gives us meaning and purpose. Many physicians who had left full-time clinical medicine missed the collegiality of the “doctors’ lounge.” Throughout our careers, we are part of a cohort: our medical school class, our residency partners, our hospital staff—we all crave community. With 36% of US physicians older than age 55 and 240,000 retired doctors in the country, we realized a motivated, previously untapped workforce could be marshaled to form a community to serve the most vulnerable among us.⁵

At the same time, telemedicine had come into its own. Simple technology could enable us to see each other on smartphones and computers and even perform portions of a physical examination from afar.

We realized we could marry opportunity (the workforce), need (underserved populations across the country), and technology. The Harvard Medical School Center Primary Care supported a feasibility study, and the MAVEN Project began “seeing” patients in 2016.

A model of hope

The MAVEN Project matches physician volunteers with safety net clinics serving patients in need and provides malpractice insurance and a Health Information Portability and Accountability Act–compliant technology platform to facilitate remote communication. Our volunteers mentor and educate primary care providers in the field and offer both immediate and asynchronous advisory consults. Clinic providers can group cases for discussion, ask urgent questions, or receive advice and support for the day-to-day challenges facing clinicians today. Clinics choose educational topics, focusing on tools needed for patient care rather than esoteric mechanisms of disease. Patients receive best-in-class care conveniently and locally, and by making volunteering easy, we build partnerships that augment patient and provider satisfaction, support long-term capacity building, and improve service delivery.

Our volunteer physicians now represent more than 30 medical specialties and 25 medical schools, and we have completed more than 2,000 consultations to date. Our clinics are located in 6 states (California, Florida, Massachusetts, New York, South Dakota, and Washington), and thanks to our model, physician state of licensure is not an impediment to volunteering. Several colleagues in our specialty are providing advice in women’s health.

Driving innovative solutions

Elizabeth Kopin, MD, an ObGyn who practiced for 28 years in Worcester, Massachusetts, and volunteers for the MAVEN Project, eloquently described in correspondence with Project coordinators the spirit that embodies the pursuit of medicine and the organization’s mission. As Dr. Kopin stated, “The driving force behind my entering medicine was to help people in an essential and meaningful way. I was especially driven to participate in the care of women. I wanted to gain knowledge and skills to help women with health care throughout their lives.”

Dr. Kopin’s capacity to care for patients in the clinic and hospital was progressively reduced as her multiple sclerosis advanced. As a result, she retired from clinical practice, but her desire to participate and contribute to medicine with the passion with which she entered it remained.

Her father was an internist who started a charitable clinic in Georgia. Like her father, Dr. Kopin began her medical career in academic medicine. Her father felt that his last 15 years in medicine were the most meaningful of his career because of his work with underserved populations. Dr. Kopin is following in his footsteps. For her, “Looking for a telehealth vehicle helping communities in need gives me the opportunity to use my abilities in the best way possible.” Dr. Kopin also stated, “Helping the underserved was something I wanted to devote my time to and The MAVEN Project has given me that possibility.”

We like to think of ourselves as Match. com meets the Peace Corps, with the goal to reach underserved patients in all 50 states in both rural and urban communities. We ask for as little as 4 hours of your time per month, and all you need is a computer or smartphone and a medical license. We welcome volunteers in active or part-time practice, academics, and industry: your years of wisdom are invaluable.

The vast complexities of the US health care system are by no measure easy to address, but standing by and allowing a fractured system to rupture is not an option. Each of us has an expertise and an opportunity to make incremental steps to ensure that those who need health care do not slip through the cracks. Dr. Kopin and I are fortunate to have a skill to help others and, in the MAVEN Project, a robust, dedicated network of individuals who share our vision.

There are many who have and continue to inspire a guiding conscience to serve beyond oneself. George H.W. Bush said it best when explaining why he founded the Points of Light organization nearly 3 decades ago⁶:

I have pursued life itself over many years now and with varying degrees of happiness. Some of my happiness still comes from trying to be in my own small way a true “point of light.” I believe I was right when I said, as President, there can be no definition of a successful life that does not include service to others. So I do that now, and I gain happiness. I do not seek a Pulitzer Prize. I do not want press attention…. I have found happiness. I no longer pursue it, for it is mine.

Please join us on our mission!

How to join

We are actively seeking specialty and primary care physicians to provide advisory consultations, mentorship, and education via telehealth technology. We welcome physician volunteers who:

• are newly retired, semi-retired, in industry, or in clinical practice
• have a minimum of 2 years of clinical practice experience
• have been active in the medical community in the past 3 years
• have an active or volunteer US medical license (any state)
• are able to provide 3 professional references
• are willing to commit a minimum of 4 hours per month for 6 months.

Visit us online to complete our physician volunteer inquiry form (https://www.mavenproject.org/work-with-us/#wwu-volunteer-as-a-physician-lightblue).

Share your thoughts! Send your Letter to the Editor to rbarbieri@mdedge.com. Please include your name and the city and state in which you practice.

Practicing in the field of obstetrics and gynecology affords us a special privilege: we are part of the most important and unforgettable events in our patients’ lives, both in sickness and in health. Along with the great joys we share comes profound responsibility and the recognition that we are only as effective as the team with whom we work. Although we live in a country that is home to some of the best health care systems in the world, the maternal mortality rates and disease burden among women in underserved communities belie this fact. A University of Washington study demonstrated a more than 20-year gap in life expectancy between wealthy and poor communities in the United States from 1980 to 2014.¹ Not surprisingly, access to medical care was a contributing factor.

Poverty only partly explains this disparity. Racial differences are at play as well. In 1992, a seminal study by Schoendorf and colleagues² demonstrated that the death rates of babies born to educated African American parents were higher due to lower birth weights. Concern recently has been amplified, and many lay publications have publicly raised the alarm.³ Several states have started investigating the causes, and the American College of Obstetrics and Gynecology, as well as other organizations, are studying possible solutions.

With nearly 50% of US births financed by Medicaid,⁵ there was great hope that the Patient Protection and Affordable Care Act and expansion of Medicaid would result in improved access and quality of health care for underserved patients; however, it has become apparent that coverage did not confer improved access to quality care, especially for medical specialties.

Urban and rural poor populations generally seek medical services from safety net clinics staffed by midlevel and physician primary care providers whose tight schedules, documentation demands, and low reimbursement rates are coupled with complex medical and socioeconomic patient populations. While these providers may be skilled in basic primary care, their patients often present with conditions outside their scope of practice. Our country’s growing physician shortage, along with patient location and personal logistics, adds to the challenges for patients and providers alike. And who among us is not asked several times a week, even by our well-insured patients, for a primary care or specialist physician recommendation? The barriers for seeking medical care in rural populations are even greater, as local hospitals and clinics are closing at an alarming rate.

Alumni at work

Communities of physicians across the country recognize both the access problem and the potential to create solutions. Organizations such as Project ECHO, launched in 2003 through the University of New Mexico, connect rural providers with university physicians to aid in treatment of hepatitis C and other illnesses.

As the date for implementation of the Patient Protection and Affordable Care Act approached, a group of medical school alumni leaders recognized that we could come together and offer our services to address growing health care disparities. Galvanized by the challenge, the Medical Alumni Volunteer Expert Network, or MAVEN Project, was, in our parlance, “born.”

While the concept of the MAVEN Project was germinating, we interviewed numerous colleagues for advice and input and were struck by their desire—especially among the newly retired—to continue to give back. Medicine is a calling, not just a job, and for many of us the joy of helping—the exhilaration of that first birth that sold us on our specialty—gives us meaning and purpose. Many physicians who had left full-time clinical medicine missed the collegiality of the “doctors’ lounge.” Throughout our careers, we are part of a cohort: our medical school class, our residency partners, our hospital staff—we all crave community. With 36% of US physicians older than age 55 and 240,000 retired doctors in the country, we realized a motivated, previously untapped workforce could be marshaled to form a community to serve the most vulnerable among us.⁵

At the same time, telemedicine had come into its own. Simple technology could enable us to see each other on smartphones and computers and even perform portions of a physical examination from afar.

We realized we could marry opportunity (the workforce), need (underserved populations across the country), and technology. The Harvard Medical School Center Primary Care supported a feasibility study, and the MAVEN Project began “seeing” patients in 2016.

A model of hope

The MAVEN Project matches physician volunteers with safety net clinics serving patients in need and provides malpractice insurance and a Health Information Portability and Accountability Act–compliant technology platform to facilitate remote communication. Our volunteers mentor and educate primary care providers in the field and offer both immediate and asynchronous advisory consults. Clinic providers can group cases for discussion, ask urgent questions, or receive advice and support for the day-to-day challenges facing clinicians today. Clinics choose educational topics, focusing on tools needed for patient care rather than esoteric mechanisms of disease. Patients receive best-in-class care conveniently and locally, and by making volunteering easy, we build partnerships that augment patient and provider satisfaction, support long-term capacity building, and improve service delivery.

Our volunteer physicians now represent more than 30 medical specialties and 25 medical schools, and we have completed more than 2,000 consultations to date. Our clinics are located in 6 states (California, Florida, Massachusetts, New York, South Dakota, and Washington), and thanks to our model, physician state of licensure is not an impediment to volunteering. Several colleagues in our specialty are providing advice in women’s health.

Driving innovative solutions

Elizabeth Kopin, MD, an ObGyn who practiced for 28 years in Worcester, Massachusetts, and volunteers for the MAVEN Project, eloquently described in correspondence with Project coordinators the spirit that embodies the pursuit of medicine and the organization’s mission. As Dr. Kopin stated, “The driving force behind my entering medicine was to help people in an essential and meaningful way. I was especially driven to participate in the care of women. I wanted to gain knowledge and skills to help women with health care throughout their lives.”

Dr. Kopin’s capacity to care for patients in the clinic and hospital was progressively reduced as her multiple sclerosis advanced. As a result, she retired from clinical practice, but her desire to participate and contribute to medicine with the passion with which she entered it remained.

Her father was an internist who started a charitable clinic in Georgia. Like her father, Dr. Kopin began her medical career in academic medicine. Her father felt that his last 15 years in medicine were the most meaningful of his career because of his work with underserved populations. Dr. Kopin is following in his footsteps. For her, “Looking for a telehealth vehicle helping communities in need gives me the opportunity to use my abilities in the best way possible.” Dr. Kopin also stated, “Helping the underserved was something I wanted to devote my time to and The MAVEN Project has given me that possibility.”

We like to think of ourselves as Match. com meets the Peace Corps, with the goal to reach underserved patients in all 50 states in both rural and urban communities. We ask for as little as 4 hours of your time per month, and all you need is a computer or smartphone and a medical license. We welcome volunteers in active or part-time practice, academics, and industry: your years of wisdom are invaluable.

The vast complexities of the US health care system are by no measure easy to address, but standing by and allowing a fractured system to rupture is not an option. Each of us has an expertise and an opportunity to make incremental steps to ensure that those who need health care do not slip through the cracks. Dr. Kopin and I are fortunate to have a skill to help others and, in the MAVEN Project, a robust, dedicated network of individuals who share our vision.

There are many who have and continue to inspire a guiding conscience to serve beyond oneself. George H.W. Bush said it best when explaining why he founded the Points of Light organization nearly 3 decades ago⁶:

I have pursued life itself over many years now and with varying degrees of happiness. Some of my happiness still comes from trying to be in my own small way a true “point of light.” I believe I was right when I said, as President, there can be no definition of a successful life that does not include service to others. So I do that now, and I gain happiness. I do not seek a Pulitzer Prize. I do not want press attention…. I have found happiness. I no longer pursue it, for it is mine.

Please join us on our mission!

How to join

We are actively seeking specialty and primary care physicians to provide advisory consultations, mentorship, and education via telehealth technology. We welcome physician volunteers who:

• are newly retired, semi-retired, in industry, or in clinical practice
• have a minimum of 2 years of clinical practice experience
• have been active in the medical community in the past 3 years
• have an active or volunteer US medical license (any state)
• are able to provide 3 professional references
• are willing to commit a minimum of 4 hours per month for 6 months.

Visit us online to complete our physician volunteer inquiry form (https://www.mavenproject.org/work-with-us/#wwu-volunteer-as-a-physician-lightblue).

Share your thoughts! Send your Letter to the Editor to rbarbieri@mdedge.com. Please include your name and the city and state in which you practice.

The European Commission has approved a new indication for daratumumab (Darzalex), according to the manufacturer.

The drug is now authorized for use in combination with bortezomib, melphalan, and prednisone (VMP) to treat adults with newly diagnosed multiple myeloma (MM) who are ineligible for autologous stem cell transplant, according to a press release published on the Genmab website.

Daratumumab was previously approved by the European Commission (EC) for use in combination with lenalidomide and dexamethasone or bortezomib and dexamethasone to treat adults with MM who have received at least one prior therapy.

In addition, daratumumab is approved by the EC as monotherapy for adults with relapsed and refractory MM whose prior therapy included a proteasome inhibitor and an immunomodulatory agent and who had disease progression on their last therapy.

The EC’s latest approval for daratumumab is based on results from the phase 3 ALCYONE trial. Results from this study were presented at the 2017 annual meeting of the American Society of Hematology and simultaneously published in the New England Journal of Medicine.

ALCYONE enrolled 706 patients with newly diagnosed MM who were not eligible for high-dose chemotherapy with autologous stem cell transplant. Patients were randomized to receive VMP or daratumumab plus VMP (D-VMP).

The overall response rates were 91% in the D-VMP arm and 74% in the VMP arm (P less than.0001), and rates of complete response were 43% and 24%, respectively. Rates of minimal residual disease negativity were 22% and 6%, respectively.

jensmith@mdedge.com

The European Commission has approved a new indication for daratumumab (Darzalex), according to the manufacturer.

The drug is now authorized for use in combination with bortezomib, melphalan, and prednisone (VMP) to treat adults with newly diagnosed multiple myeloma (MM) who are ineligible for autologous stem cell transplant, according to a press release published on the Genmab website.

Daratumumab was previously approved by the European Commission (EC) for use in combination with lenalidomide and dexamethasone or bortezomib and dexamethasone to treat adults with MM who have received at least one prior therapy.

In addition, daratumumab is approved by the EC as monotherapy for adults with relapsed and refractory MM whose prior therapy included a proteasome inhibitor and an immunomodulatory agent and who had disease progression on their last therapy.

The EC’s latest approval for daratumumab is based on results from the phase 3 ALCYONE trial. Results from this study were presented at the 2017 annual meeting of the American Society of Hematology and simultaneously published in the New England Journal of Medicine.

ALCYONE enrolled 706 patients with newly diagnosed MM who were not eligible for high-dose chemotherapy with autologous stem cell transplant. Patients were randomized to receive VMP or daratumumab plus VMP (D-VMP).

The overall response rates were 91% in the D-VMP arm and 74% in the VMP arm (P less than.0001), and rates of complete response were 43% and 24%, respectively. Rates of minimal residual disease negativity were 22% and 6%, respectively.

jensmith@mdedge.com

The European Commission has approved a new indication for daratumumab (Darzalex), according to the manufacturer.

The drug is now authorized for use in combination with bortezomib, melphalan, and prednisone (VMP) to treat adults with newly diagnosed multiple myeloma (MM) who are ineligible for autologous stem cell transplant, according to a press release published on the Genmab website.

Daratumumab was previously approved by the European Commission (EC) for use in combination with lenalidomide and dexamethasone or bortezomib and dexamethasone to treat adults with MM who have received at least one prior therapy.

In addition, daratumumab is approved by the EC as monotherapy for adults with relapsed and refractory MM whose prior therapy included a proteasome inhibitor and an immunomodulatory agent and who had disease progression on their last therapy.

The EC’s latest approval for daratumumab is based on results from the phase 3 ALCYONE trial. Results from this study were presented at the 2017 annual meeting of the American Society of Hematology and simultaneously published in the New England Journal of Medicine.

ALCYONE enrolled 706 patients with newly diagnosed MM who were not eligible for high-dose chemotherapy with autologous stem cell transplant. Patients were randomized to receive VMP or daratumumab plus VMP (D-VMP).

The overall response rates were 91% in the D-VMP arm and 74% in the VMP arm (P less than.0001), and rates of complete response were 43% and 24%, respectively. Rates of minimal residual disease negativity were 22% and 6%, respectively.

jensmith@mdedge.com

Approximately one-third of children seen for head trauma visits in EDs underwent CT scans over a 9-year period in the United States, despite quality improvement initiatives to reduce unnecessary scans, based on a data from a cross-sectional survey published in Pediatrics.

©Thinkstock.com

“Computed tomography (CT) is the reference standard to provide a rapid and definitive diagnosis of intracranial pathology but must be balanced against the risks of radiation-induced malignancy,” wrote Brett Burstein, MD, PhD, of Harvard T.H. Chan School of Public Health, Cambridge, Mass., and his colleagues.

The researchers reviewed data from National Hospital Ambulatory Care Medical Survey database of nationally representative ED visits by children younger than 18 years for head trauma from 2007 to 2015. The median age of the patients was 6 years; 61% were boys. Approximately 88% were seen in nonteaching or nonpediatric hospitals.

During the 9-year period, 32% of 3,054 children underwent head CT scans; the 3,054 represented an estimated 14.3 million children making pediatric ED visits for head trauma. No significant differences were noted from year to year after the researchers controlled for confounding patient and ED factors.

Overall, use of CT was associated with patient’s age 2 years and older (adjusted odds ratio 1.51), white race (aOR 1.43), highest level of triage (aOR 8.24), and treatment at a nonteaching or nonpediatric hospital (aOR 1.47 and 1.53, respectively).

No significant differences in CT use were observed when the researchers compared the periods before (2007-2009) and after (2010-2015) the introduction of the Pediatric Emergency Care Applied Research Network (PECARN) rules – a clinical prediction protocol to assess head injuries in children in an ED setting. The unadjusted proportion of children who underwent CTs during the before PECARN and after PECARN periods was 33% and 31%, respectively.

“The finding of no decrease in CT neuroimaging during the 9-year study period, and particularly after the publication of the PECARN rules in 2009, was counter to the a priori hypothesis of this study,” Dr. Burstein and his associates noted.

The findings were limited by several factors including the lack of data on the severity of the head injuries, data on repeat visits, and potential misclassification of hospitals, they said. However, the results highlight the need for targeted interventions to disseminate the latest clinical decisions into practice.

Dr. Burstein and his associates had no financial conflicts to disclose.

SOURCE: Burstein B al. Pediatrics. 2018 Sept 4. doi: 10.1542/peds.2018-0814.

Approximately one-third of children seen for head trauma visits in EDs underwent CT scans over a 9-year period in the United States, despite quality improvement initiatives to reduce unnecessary scans, based on a data from a cross-sectional survey published in Pediatrics.

©Thinkstock.com

“Computed tomography (CT) is the reference standard to provide a rapid and definitive diagnosis of intracranial pathology but must be balanced against the risks of radiation-induced malignancy,” wrote Brett Burstein, MD, PhD, of Harvard T.H. Chan School of Public Health, Cambridge, Mass., and his colleagues.

The researchers reviewed data from National Hospital Ambulatory Care Medical Survey database of nationally representative ED visits by children younger than 18 years for head trauma from 2007 to 2015. The median age of the patients was 6 years; 61% were boys. Approximately 88% were seen in nonteaching or nonpediatric hospitals.

During the 9-year period, 32% of 3,054 children underwent head CT scans; the 3,054 represented an estimated 14.3 million children making pediatric ED visits for head trauma. No significant differences were noted from year to year after the researchers controlled for confounding patient and ED factors.

Overall, use of CT was associated with patient’s age 2 years and older (adjusted odds ratio 1.51), white race (aOR 1.43), highest level of triage (aOR 8.24), and treatment at a nonteaching or nonpediatric hospital (aOR 1.47 and 1.53, respectively).

No significant differences in CT use were observed when the researchers compared the periods before (2007-2009) and after (2010-2015) the introduction of the Pediatric Emergency Care Applied Research Network (PECARN) rules – a clinical prediction protocol to assess head injuries in children in an ED setting. The unadjusted proportion of children who underwent CTs during the before PECARN and after PECARN periods was 33% and 31%, respectively.

“The finding of no decrease in CT neuroimaging during the 9-year study period, and particularly after the publication of the PECARN rules in 2009, was counter to the a priori hypothesis of this study,” Dr. Burstein and his associates noted.

The findings were limited by several factors including the lack of data on the severity of the head injuries, data on repeat visits, and potential misclassification of hospitals, they said. However, the results highlight the need for targeted interventions to disseminate the latest clinical decisions into practice.

Dr. Burstein and his associates had no financial conflicts to disclose.

SOURCE: Burstein B al. Pediatrics. 2018 Sept 4. doi: 10.1542/peds.2018-0814.

Approximately one-third of children seen for head trauma visits in EDs underwent CT scans over a 9-year period in the United States, despite quality improvement initiatives to reduce unnecessary scans, based on a data from a cross-sectional survey published in Pediatrics.

©Thinkstock.com

“Computed tomography (CT) is the reference standard to provide a rapid and definitive diagnosis of intracranial pathology but must be balanced against the risks of radiation-induced malignancy,” wrote Brett Burstein, MD, PhD, of Harvard T.H. Chan School of Public Health, Cambridge, Mass., and his colleagues.

The researchers reviewed data from National Hospital Ambulatory Care Medical Survey database of nationally representative ED visits by children younger than 18 years for head trauma from 2007 to 2015. The median age of the patients was 6 years; 61% were boys. Approximately 88% were seen in nonteaching or nonpediatric hospitals.

During the 9-year period, 32% of 3,054 children underwent head CT scans; the 3,054 represented an estimated 14.3 million children making pediatric ED visits for head trauma. No significant differences were noted from year to year after the researchers controlled for confounding patient and ED factors.

Overall, use of CT was associated with patient’s age 2 years and older (adjusted odds ratio 1.51), white race (aOR 1.43), highest level of triage (aOR 8.24), and treatment at a nonteaching or nonpediatric hospital (aOR 1.47 and 1.53, respectively).

No significant differences in CT use were observed when the researchers compared the periods before (2007-2009) and after (2010-2015) the introduction of the Pediatric Emergency Care Applied Research Network (PECARN) rules – a clinical prediction protocol to assess head injuries in children in an ED setting. The unadjusted proportion of children who underwent CTs during the before PECARN and after PECARN periods was 33% and 31%, respectively.

“The finding of no decrease in CT neuroimaging during the 9-year study period, and particularly after the publication of the PECARN rules in 2009, was counter to the a priori hypothesis of this study,” Dr. Burstein and his associates noted.

The findings were limited by several factors including the lack of data on the severity of the head injuries, data on repeat visits, and potential misclassification of hospitals, they said. However, the results highlight the need for targeted interventions to disseminate the latest clinical decisions into practice.

Dr. Burstein and his associates had no financial conflicts to disclose.

SOURCE: Burstein B al. Pediatrics. 2018 Sept 4. doi: 10.1542/peds.2018-0814.

Expression of programmed death-1 (PD1) mRNA may predict outcomes after anti-PD1 therapy across cancer types, according to investigators.

High levels of PD1 mRNA were significantly associated with response to anti-PD1 monotherapy, investigators found in an analysis of tumor samples from 117 patients with advanced cancers who had received either nivolumab or pembrolizumab.

Further validation of PD1 mRNA is warranted to help select patients who might benefit from an anti-PD1 treatment strategy, wrote investigator Aleix Prat, MD, PhD, of Hospital Clínic of Barcelona, and his coinvestigators.

“Identification of reproducible biomarkers that can be applied to predict benefit of anti-PD1 monotherapy might be of clinical value,” Dr. Prat and his coinvestigators note. The report is in Annals of Oncology.

Previous studies support use of PDL1 expression by immunohistochemistry as a biomarker for pembrolizumab in non–small-cell lung cancer; however, that biomarker has some technical limitations, and has not been predictive in other cancer types and with other anti-PD1 drugs including nivolumab, Dr. Prat and his coinvestigators said.

The 117 tumor samples evaluated for PD1 mRNA expression comprised 59 advanced melanomas, 32 non–small-cell lung cancers, 14 renal cell cancers, and 12 other tumors, according to the report. Sixty-two of the patients had been treated with pembrolizumab, and 55 received nivolumab.

About one-quarter of the samples (28.2%) were classified as “PD1-high” with a preestablished cutoff value developed by Dr. Prat and his coinvestigators.

The overall response rate was 51.5% for the patients who had PD1-high tumors, versus 23.8% for the remaining tumors (P less than .001). Those non-PD1-high tumors, when grouped as PD1-intermediate and PD1-low, had overall response rates of 26.6% and 15.0%, respectively.

Median progression-free survival was 8.17 months for PD1-high tumors and 3.18 months for the rest of the tumors (P = .011), the report shows. Similarly, overall survival was a median of 23.4 months for PD1-high tumors and 14.9 months for the rest (P = .330).

Dr. Prat and his colleagues detailed earlier investigations validating PD1 mRNA as a biomarker, including an analysis of PD1 and immune-related gene expression in 10,078 samples from 34 cancer types in The Cancer Genome Atlas.

In that analysis, PD1 was strongly correlated with a group of 30 genes that were “significantly enriched” in biological processes including CD8-T-cell activation, the investigators said.

Moreover, high levels of PD1 mRNA expression were strongly correlated with overall response rates reported in the literature for anti-PD1 monotherapy, they added.

They also reported results of an analysis they used to develop the PD1-high cutoff value. That analysis was based on PD1 mRNA expression in 773 tumor samples across 17 tumor types.

“Our results are consistent with the hypothesis that identification of a preexisting and stable adaptive immune response using PD1 mRNA expression predicts outcome across cancer-types following anti-PD1 monotherapy,” the researchers wrote.

The work was partially sponsored by Instituto de Salud Carlos III, Spanish Society of Medical Oncology, Banco Bilbao Vizcaya Argentaria Foundation, Pas a Pas, Save the Mama, and the Breast Cancer Research Foundation. Dr. Prat disclosed an advisory role with Nanostring Technologies.

SOURCE: Paré L et al. Ann Oncol. 2018 Aug 27. doi: 10.1093/annonc/mdy335.

Expression of programmed death-1 (PD1) mRNA may predict outcomes after anti-PD1 therapy across cancer types, according to investigators.

High levels of PD1 mRNA were significantly associated with response to anti-PD1 monotherapy, investigators found in an analysis of tumor samples from 117 patients with advanced cancers who had received either nivolumab or pembrolizumab.

Further validation of PD1 mRNA is warranted to help select patients who might benefit from an anti-PD1 treatment strategy, wrote investigator Aleix Prat, MD, PhD, of Hospital Clínic of Barcelona, and his coinvestigators.

“Identification of reproducible biomarkers that can be applied to predict benefit of anti-PD1 monotherapy might be of clinical value,” Dr. Prat and his coinvestigators note. The report is in Annals of Oncology.

Previous studies support use of PDL1 expression by immunohistochemistry as a biomarker for pembrolizumab in non–small-cell lung cancer; however, that biomarker has some technical limitations, and has not been predictive in other cancer types and with other anti-PD1 drugs including nivolumab, Dr. Prat and his coinvestigators said.

The 117 tumor samples evaluated for PD1 mRNA expression comprised 59 advanced melanomas, 32 non–small-cell lung cancers, 14 renal cell cancers, and 12 other tumors, according to the report. Sixty-two of the patients had been treated with pembrolizumab, and 55 received nivolumab.

About one-quarter of the samples (28.2%) were classified as “PD1-high” with a preestablished cutoff value developed by Dr. Prat and his coinvestigators.

The overall response rate was 51.5% for the patients who had PD1-high tumors, versus 23.8% for the remaining tumors (P less than .001). Those non-PD1-high tumors, when grouped as PD1-intermediate and PD1-low, had overall response rates of 26.6% and 15.0%, respectively.

Median progression-free survival was 8.17 months for PD1-high tumors and 3.18 months for the rest of the tumors (P = .011), the report shows. Similarly, overall survival was a median of 23.4 months for PD1-high tumors and 14.9 months for the rest (P = .330).

Dr. Prat and his colleagues detailed earlier investigations validating PD1 mRNA as a biomarker, including an analysis of PD1 and immune-related gene expression in 10,078 samples from 34 cancer types in The Cancer Genome Atlas.

In that analysis, PD1 was strongly correlated with a group of 30 genes that were “significantly enriched” in biological processes including CD8-T-cell activation, the investigators said.

Moreover, high levels of PD1 mRNA expression were strongly correlated with overall response rates reported in the literature for anti-PD1 monotherapy, they added.

They also reported results of an analysis they used to develop the PD1-high cutoff value. That analysis was based on PD1 mRNA expression in 773 tumor samples across 17 tumor types.

“Our results are consistent with the hypothesis that identification of a preexisting and stable adaptive immune response using PD1 mRNA expression predicts outcome across cancer-types following anti-PD1 monotherapy,” the researchers wrote.

The work was partially sponsored by Instituto de Salud Carlos III, Spanish Society of Medical Oncology, Banco Bilbao Vizcaya Argentaria Foundation, Pas a Pas, Save the Mama, and the Breast Cancer Research Foundation. Dr. Prat disclosed an advisory role with Nanostring Technologies.

SOURCE: Paré L et al. Ann Oncol. 2018 Aug 27. doi: 10.1093/annonc/mdy335.

Expression of programmed death-1 (PD1) mRNA may predict outcomes after anti-PD1 therapy across cancer types, according to investigators.

High levels of PD1 mRNA were significantly associated with response to anti-PD1 monotherapy, investigators found in an analysis of tumor samples from 117 patients with advanced cancers who had received either nivolumab or pembrolizumab.

Further validation of PD1 mRNA is warranted to help select patients who might benefit from an anti-PD1 treatment strategy, wrote investigator Aleix Prat, MD, PhD, of Hospital Clínic of Barcelona, and his coinvestigators.

“Identification of reproducible biomarkers that can be applied to predict benefit of anti-PD1 monotherapy might be of clinical value,” Dr. Prat and his coinvestigators note. The report is in Annals of Oncology.

Previous studies support use of PDL1 expression by immunohistochemistry as a biomarker for pembrolizumab in non–small-cell lung cancer; however, that biomarker has some technical limitations, and has not been predictive in other cancer types and with other anti-PD1 drugs including nivolumab, Dr. Prat and his coinvestigators said.

The 117 tumor samples evaluated for PD1 mRNA expression comprised 59 advanced melanomas, 32 non–small-cell lung cancers, 14 renal cell cancers, and 12 other tumors, according to the report. Sixty-two of the patients had been treated with pembrolizumab, and 55 received nivolumab.

About one-quarter of the samples (28.2%) were classified as “PD1-high” with a preestablished cutoff value developed by Dr. Prat and his coinvestigators.

The overall response rate was 51.5% for the patients who had PD1-high tumors, versus 23.8% for the remaining tumors (P less than .001). Those non-PD1-high tumors, when grouped as PD1-intermediate and PD1-low, had overall response rates of 26.6% and 15.0%, respectively.

Median progression-free survival was 8.17 months for PD1-high tumors and 3.18 months for the rest of the tumors (P = .011), the report shows. Similarly, overall survival was a median of 23.4 months for PD1-high tumors and 14.9 months for the rest (P = .330).

Dr. Prat and his colleagues detailed earlier investigations validating PD1 mRNA as a biomarker, including an analysis of PD1 and immune-related gene expression in 10,078 samples from 34 cancer types in The Cancer Genome Atlas.

In that analysis, PD1 was strongly correlated with a group of 30 genes that were “significantly enriched” in biological processes including CD8-T-cell activation, the investigators said.

Moreover, high levels of PD1 mRNA expression were strongly correlated with overall response rates reported in the literature for anti-PD1 monotherapy, they added.

They also reported results of an analysis they used to develop the PD1-high cutoff value. That analysis was based on PD1 mRNA expression in 773 tumor samples across 17 tumor types.

“Our results are consistent with the hypothesis that identification of a preexisting and stable adaptive immune response using PD1 mRNA expression predicts outcome across cancer-types following anti-PD1 monotherapy,” the researchers wrote.

The work was partially sponsored by Instituto de Salud Carlos III, Spanish Society of Medical Oncology, Banco Bilbao Vizcaya Argentaria Foundation, Pas a Pas, Save the Mama, and the Breast Cancer Research Foundation. Dr. Prat disclosed an advisory role with Nanostring Technologies.

SOURCE: Paré L et al. Ann Oncol. 2018 Aug 27. doi: 10.1093/annonc/mdy335.

Physician groups are expressing concerns regarding a new policy that will allow indication-based formulary design in the Medicare Part D prescription drug benefit.

Kenishirotie/Thinkstock

The Centers for Medicare & Medicaid Services announced the new policy in an Aug. 29 memo to Part D plan sponsors.

According to a fact sheet issued by CMS on the same day, indication-based formulary design “is a formulary management tool that allows health plans to tailor on-formulary coverage of drugs predicated on specific indications.”

Current Part D policy requires plan sponsors to cover all Food and Drug Administration–approved indications for each drug that is on a plan formulary. Sponsors can begin to implement the new indication-based formulary design policy for plans issued in 2020.

The memo notes that if a Part D plan sponsor chooses to opt into this policy, “it must ensure that there is another therapeutically similar drug on formulary for the nonformulary indication. For example, if a tumor necrosis factor (TNF) blocker is FDA-approved for both Crohn’s disease and plaque psoriasis, but the Part D plan will include it on formulary for plaque psoriasis only, the plan must ensure that there is another TNF blocker on formulary that will be covered for Crohn’s disease.”

Beneficiaries can use the exceptions process to get coverage for a drug that has an indication not on the formulary.

“By allowing Medicare’s prescription drug plans to cover the best drug for each patient condition, plans will have more negotiating power with drug companies, which will result in lower prices for Medicare beneficiaries,” CMS Administrator Seema Verma said in a statement.

However, physician groups see this more as something that could create access issues for patients.

The “proposed changes will exacerbate many of the access issues patients currently face with plan usage of existing utilization management practices, such as step therapy,” the American College of Rheumatology said in a statement. “Unlike step therapy, which often delays effective treatments, this proposal would go even further and allow plans to remove therapies from the formulary altogether, leaving patients completely unable to access treatments that doctors and patients choose together. ... We also have concerns on what this would mean for work being done on compendia inclusion to secure off-label drug coverage if plans don’t have to cover all approved FDA-approved indications.”

The ACR called on CMS to clarify the exception process to make sure patients have access to their needed drugs.

The American Medical Association agreed.

“Under the plan, Medicare patients will face increased challenges as they navigate health plans to make sure that their needed drug is on their selected formulary, which can change based on what health conditions they have,” AMA President Barbara McAneny, MD, said in a statement. “While the CMS notice included a statement that plans had to include information addressing indication-based formularies in materials provided to prospective enrollees, that is not much help to patients who are not sophisticated in how formularies work.”

Dr. McAneny added that it will be even more difficult for physicians who are working with patients to get them on the best medicines covered by the patient’s formulary.

“Physicians already lack ready access to accurate formulary information – preferred/tier status, on/off formulary, PA [prior authorization] and step therapy requirements – at the point of care in their EHRs,” she said. “These transparency problems will expand by an order of magnitude by the complications this change introduces.”

She also noted that it could be difficult for patients who have multiple chronic conditions to find a drug plan that covers the range of their medications, although CMS said the move is expected to increase the number of drugs available on a given plan’s formulary.

gtwachtman@mdedge.com

Physician groups are expressing concerns regarding a new policy that will allow indication-based formulary design in the Medicare Part D prescription drug benefit.

Kenishirotie/Thinkstock

The Centers for Medicare & Medicaid Services announced the new policy in an Aug. 29 memo to Part D plan sponsors.

According to a fact sheet issued by CMS on the same day, indication-based formulary design “is a formulary management tool that allows health plans to tailor on-formulary coverage of drugs predicated on specific indications.”

Current Part D policy requires plan sponsors to cover all Food and Drug Administration–approved indications for each drug that is on a plan formulary. Sponsors can begin to implement the new indication-based formulary design policy for plans issued in 2020.

The memo notes that if a Part D plan sponsor chooses to opt into this policy, “it must ensure that there is another therapeutically similar drug on formulary for the nonformulary indication. For example, if a tumor necrosis factor (TNF) blocker is FDA-approved for both Crohn’s disease and plaque psoriasis, but the Part D plan will include it on formulary for plaque psoriasis only, the plan must ensure that there is another TNF blocker on formulary that will be covered for Crohn’s disease.”

Beneficiaries can use the exceptions process to get coverage for a drug that has an indication not on the formulary.

“By allowing Medicare’s prescription drug plans to cover the best drug for each patient condition, plans will have more negotiating power with drug companies, which will result in lower prices for Medicare beneficiaries,” CMS Administrator Seema Verma said in a statement.

However, physician groups see this more as something that could create access issues for patients.

The “proposed changes will exacerbate many of the access issues patients currently face with plan usage of existing utilization management practices, such as step therapy,” the American College of Rheumatology said in a statement. “Unlike step therapy, which often delays effective treatments, this proposal would go even further and allow plans to remove therapies from the formulary altogether, leaving patients completely unable to access treatments that doctors and patients choose together. ... We also have concerns on what this would mean for work being done on compendia inclusion to secure off-label drug coverage if plans don’t have to cover all approved FDA-approved indications.”

The ACR called on CMS to clarify the exception process to make sure patients have access to their needed drugs.

The American Medical Association agreed.

“Under the plan, Medicare patients will face increased challenges as they navigate health plans to make sure that their needed drug is on their selected formulary, which can change based on what health conditions they have,” AMA President Barbara McAneny, MD, said in a statement. “While the CMS notice included a statement that plans had to include information addressing indication-based formularies in materials provided to prospective enrollees, that is not much help to patients who are not sophisticated in how formularies work.”

Dr. McAneny added that it will be even more difficult for physicians who are working with patients to get them on the best medicines covered by the patient’s formulary.

“Physicians already lack ready access to accurate formulary information – preferred/tier status, on/off formulary, PA [prior authorization] and step therapy requirements – at the point of care in their EHRs,” she said. “These transparency problems will expand by an order of magnitude by the complications this change introduces.”

She also noted that it could be difficult for patients who have multiple chronic conditions to find a drug plan that covers the range of their medications, although CMS said the move is expected to increase the number of drugs available on a given plan’s formulary.

gtwachtman@mdedge.com

Physician groups are expressing concerns regarding a new policy that will allow indication-based formulary design in the Medicare Part D prescription drug benefit.

Kenishirotie/Thinkstock

The Centers for Medicare & Medicaid Services announced the new policy in an Aug. 29 memo to Part D plan sponsors.

According to a fact sheet issued by CMS on the same day, indication-based formulary design “is a formulary management tool that allows health plans to tailor on-formulary coverage of drugs predicated on specific indications.”

Current Part D policy requires plan sponsors to cover all Food and Drug Administration–approved indications for each drug that is on a plan formulary. Sponsors can begin to implement the new indication-based formulary design policy for plans issued in 2020.

The memo notes that if a Part D plan sponsor chooses to opt into this policy, “it must ensure that there is another therapeutically similar drug on formulary for the nonformulary indication. For example, if a tumor necrosis factor (TNF) blocker is FDA-approved for both Crohn’s disease and plaque psoriasis, but the Part D plan will include it on formulary for plaque psoriasis only, the plan must ensure that there is another TNF blocker on formulary that will be covered for Crohn’s disease.”

Beneficiaries can use the exceptions process to get coverage for a drug that has an indication not on the formulary.

“By allowing Medicare’s prescription drug plans to cover the best drug for each patient condition, plans will have more negotiating power with drug companies, which will result in lower prices for Medicare beneficiaries,” CMS Administrator Seema Verma said in a statement.

However, physician groups see this more as something that could create access issues for patients.

The “proposed changes will exacerbate many of the access issues patients currently face with plan usage of existing utilization management practices, such as step therapy,” the American College of Rheumatology said in a statement. “Unlike step therapy, which often delays effective treatments, this proposal would go even further and allow plans to remove therapies from the formulary altogether, leaving patients completely unable to access treatments that doctors and patients choose together. ... We also have concerns on what this would mean for work being done on compendia inclusion to secure off-label drug coverage if plans don’t have to cover all approved FDA-approved indications.”

The ACR called on CMS to clarify the exception process to make sure patients have access to their needed drugs.

The American Medical Association agreed.

“Under the plan, Medicare patients will face increased challenges as they navigate health plans to make sure that their needed drug is on their selected formulary, which can change based on what health conditions they have,” AMA President Barbara McAneny, MD, said in a statement. “While the CMS notice included a statement that plans had to include information addressing indication-based formularies in materials provided to prospective enrollees, that is not much help to patients who are not sophisticated in how formularies work.”

Dr. McAneny added that it will be even more difficult for physicians who are working with patients to get them on the best medicines covered by the patient’s formulary.

“Physicians already lack ready access to accurate formulary information – preferred/tier status, on/off formulary, PA [prior authorization] and step therapy requirements – at the point of care in their EHRs,” she said. “These transparency problems will expand by an order of magnitude by the complications this change introduces.”

She also noted that it could be difficult for patients who have multiple chronic conditions to find a drug plan that covers the range of their medications, although CMS said the move is expected to increase the number of drugs available on a given plan’s formulary.

gtwachtman@mdedge.com

The Food and Drug Administration has granted fast-track designation to CX-01 as a treatment for patients older than 60 years receiving induction therapy for newly diagnosed acute myeloid leukemia (AML).

CX-01 also has orphan drug designation from the FDA.

CX-01 is a polysaccharide derived from heparin thought to enhance chemotherapy by disrupting leukemia cell adhesion in bone marrow. Cantex Pharmaceuticals is conducting a randomized, phase 2b study to determine whether CX-01 can improve the efficacy of frontline chemotherapy in patients with AML.

This study builds upon results of a pilot study, which were published in Blood Advances (Blood Adv. 2018 Feb 27;2[4]:381-9). The pilot study enrolled 12 adults with newly diagnosed AML who received CX-01 as a continuous infusion for 7 days, along with standard induction chemotherapy (cytarabine and idarubicin).

The FDA’s fast-track development program is designed to expedite clinical development and submission of applications for products with the potential to treat serious or life-threatening conditions and address unmet medical needs.

jensmith@mdedge.com

The Food and Drug Administration has granted fast-track designation to CX-01 as a treatment for patients older than 60 years receiving induction therapy for newly diagnosed acute myeloid leukemia (AML).

CX-01 also has orphan drug designation from the FDA.

CX-01 is a polysaccharide derived from heparin thought to enhance chemotherapy by disrupting leukemia cell adhesion in bone marrow. Cantex Pharmaceuticals is conducting a randomized, phase 2b study to determine whether CX-01 can improve the efficacy of frontline chemotherapy in patients with AML.

This study builds upon results of a pilot study, which were published in Blood Advances (Blood Adv. 2018 Feb 27;2[4]:381-9). The pilot study enrolled 12 adults with newly diagnosed AML who received CX-01 as a continuous infusion for 7 days, along with standard induction chemotherapy (cytarabine and idarubicin).

The FDA’s fast-track development program is designed to expedite clinical development and submission of applications for products with the potential to treat serious or life-threatening conditions and address unmet medical needs.

jensmith@mdedge.com

The Food and Drug Administration has granted fast-track designation to CX-01 as a treatment for patients older than 60 years receiving induction therapy for newly diagnosed acute myeloid leukemia (AML).

CX-01 also has orphan drug designation from the FDA.

CX-01 is a polysaccharide derived from heparin thought to enhance chemotherapy by disrupting leukemia cell adhesion in bone marrow. Cantex Pharmaceuticals is conducting a randomized, phase 2b study to determine whether CX-01 can improve the efficacy of frontline chemotherapy in patients with AML.

This study builds upon results of a pilot study, which were published in Blood Advances (Blood Adv. 2018 Feb 27;2[4]:381-9). The pilot study enrolled 12 adults with newly diagnosed AML who received CX-01 as a continuous infusion for 7 days, along with standard induction chemotherapy (cytarabine and idarubicin).

The FDA’s fast-track development program is designed to expedite clinical development and submission of applications for products with the potential to treat serious or life-threatening conditions and address unmet medical needs.

jensmith@mdedge.com