Sudhof LS, Shainker SA, Einerson BD. Tranexamic acid in the routine treatment of postpartum hemorrhage in the United States: a cost-effectiveness analysis. Am J Obstet Gynecol. Published online June 18, 2019. doi.org/10.1016/j.ajog.2019.06.030.

EXPERT COMMENTARY

Postpartum hemorrhage is a leading cause of morbidity and mortality in the United States. The World Maternal Antifibrinolytic (WOMAN) trial showed that the use of TXA, an antifibrinolytic agent, for PPH decreases hemorrhage-related mortality and laparotomy. Routine use of TXA for PPH has demonstrated cost-effectiveness in low-resource countries, where hemorrhage-related mortality rates are higher than in the United States. This study aimed to determine if routine use of TXA for PPH in the United States also is cost-effective.

Details of the study

Sudhof and colleagues conducted a decision-tree analysis to compare the cost-effectiveness of 3 strategies regarding routine use of TXA for PPH in the United States: no TXA, TXA given at any time, and TXA given within 3 hours of delivery.

Health care system perspective. In the primary analysis, the 3 strategies were evaluated from the perspective of the health care system. Outcomes included cost, number of laparotomies, and maternal deaths from delivery until 6 weeks postpartum. Rates of hemorrhage and related complications, as well as cost assumptions, were derived from multiple US-based studies. The relative risk reduction in death and laparotomy with TXA in the United States was assumed to be similar to that found in the WOMAN trial (19% and 36%, respectively).

Societal perspective. In the secondary analysis, the 3 TXA strategies were evaluated from the societal perspective, comparing quality-adjusted life-years (QALYs) and cost per QALY. For both the primary and secondary analyses, sensitivity analyses were performed across a range of values for each input.

Main findings. Tranexamic acid use would be cost saving if the relative risk reduction for maternal death with TXA was greater than approximately 5%, which is significantly lower than that seen in the WOMAN trial (19%). The primary analysis demonstrated that—assuming a 3% rate of PPH—giving TXA to women with PPH would save $11.3 million, prevent 334 laparotomies, and avert 9 maternal deaths annually in the United States. This cost saving nearly tripled if TXA was administered within 3 hours of delivery, with 5 additional maternal deaths prevented.

Secondary analysis incorporating QALYs also showed TXA use to be cost-effective. These findings held through various sensitivity analyses.

Continue to: Study strengths and limitations...

Study strengths and limitations

This study is novel in its critical objective to determine the cost-effectiveness of routine use of TXA for PPH in the United States. Robust modeling using Monte Carlo estimation and a variety of sensitivity analyses add reliability to the authors’ findings.

This work is limited, however, by the assumptions put into the authors’ models. For example, outcome data regarding effectiveness of TXA was taken from the WOMAN trial, which was not performed within the United States. In addition, it is difficult to quantify in dollars an event as profound as a maternal death. The authors recognize that they likely underestimate the “cost” of a maternal death, but that this underestimation would only increase the cost-effectiveness of TXA.

Finally, it is important to take into account that such economic analyses are helpful to inform institutional guidelines and hemorrhage protocols, but that patient-specific decision-making should be individualized based on the clinical scenario at hand.

Sudhof LS, Shainker SA, Einerson BD. Tranexamic acid in the routine treatment of postpartum hemorrhage in the United States: a cost-effectiveness analysis. Am J Obstet Gynecol. Published online June 18, 2019. doi.org/10.1016/j.ajog.2019.06.030.

EXPERT COMMENTARY

Postpartum hemorrhage is a leading cause of morbidity and mortality in the United States. The World Maternal Antifibrinolytic (WOMAN) trial showed that the use of TXA, an antifibrinolytic agent, for PPH decreases hemorrhage-related mortality and laparotomy. Routine use of TXA for PPH has demonstrated cost-effectiveness in low-resource countries, where hemorrhage-related mortality rates are higher than in the United States. This study aimed to determine if routine use of TXA for PPH in the United States also is cost-effective.

Details of the study

Sudhof and colleagues conducted a decision-tree analysis to compare the cost-effectiveness of 3 strategies regarding routine use of TXA for PPH in the United States: no TXA, TXA given at any time, and TXA given within 3 hours of delivery.

Health care system perspective. In the primary analysis, the 3 strategies were evaluated from the perspective of the health care system. Outcomes included cost, number of laparotomies, and maternal deaths from delivery until 6 weeks postpartum. Rates of hemorrhage and related complications, as well as cost assumptions, were derived from multiple US-based studies. The relative risk reduction in death and laparotomy with TXA in the United States was assumed to be similar to that found in the WOMAN trial (19% and 36%, respectively).

Societal perspective. In the secondary analysis, the 3 TXA strategies were evaluated from the societal perspective, comparing quality-adjusted life-years (QALYs) and cost per QALY. For both the primary and secondary analyses, sensitivity analyses were performed across a range of values for each input.

Main findings. Tranexamic acid use would be cost saving if the relative risk reduction for maternal death with TXA was greater than approximately 5%, which is significantly lower than that seen in the WOMAN trial (19%). The primary analysis demonstrated that—assuming a 3% rate of PPH—giving TXA to women with PPH would save $11.3 million, prevent 334 laparotomies, and avert 9 maternal deaths annually in the United States. This cost saving nearly tripled if TXA was administered within 3 hours of delivery, with 5 additional maternal deaths prevented.

Secondary analysis incorporating QALYs also showed TXA use to be cost-effective. These findings held through various sensitivity analyses.

Continue to: Study strengths and limitations...

Study strengths and limitations

This study is novel in its critical objective to determine the cost-effectiveness of routine use of TXA for PPH in the United States. Robust modeling using Monte Carlo estimation and a variety of sensitivity analyses add reliability to the authors’ findings.

This work is limited, however, by the assumptions put into the authors’ models. For example, outcome data regarding effectiveness of TXA was taken from the WOMAN trial, which was not performed within the United States. In addition, it is difficult to quantify in dollars an event as profound as a maternal death. The authors recognize that they likely underestimate the “cost” of a maternal death, but that this underestimation would only increase the cost-effectiveness of TXA.

Finally, it is important to take into account that such economic analyses are helpful to inform institutional guidelines and hemorrhage protocols, but that patient-specific decision-making should be individualized based on the clinical scenario at hand.

Sudhof LS, Shainker SA, Einerson BD. Tranexamic acid in the routine treatment of postpartum hemorrhage in the United States: a cost-effectiveness analysis. Am J Obstet Gynecol. Published online June 18, 2019. doi.org/10.1016/j.ajog.2019.06.030.

EXPERT COMMENTARY

Postpartum hemorrhage is a leading cause of morbidity and mortality in the United States. The World Maternal Antifibrinolytic (WOMAN) trial showed that the use of TXA, an antifibrinolytic agent, for PPH decreases hemorrhage-related mortality and laparotomy. Routine use of TXA for PPH has demonstrated cost-effectiveness in low-resource countries, where hemorrhage-related mortality rates are higher than in the United States. This study aimed to determine if routine use of TXA for PPH in the United States also is cost-effective.

Details of the study

Sudhof and colleagues conducted a decision-tree analysis to compare the cost-effectiveness of 3 strategies regarding routine use of TXA for PPH in the United States: no TXA, TXA given at any time, and TXA given within 3 hours of delivery.

Health care system perspective. In the primary analysis, the 3 strategies were evaluated from the perspective of the health care system. Outcomes included cost, number of laparotomies, and maternal deaths from delivery until 6 weeks postpartum. Rates of hemorrhage and related complications, as well as cost assumptions, were derived from multiple US-based studies. The relative risk reduction in death and laparotomy with TXA in the United States was assumed to be similar to that found in the WOMAN trial (19% and 36%, respectively).

Societal perspective. In the secondary analysis, the 3 TXA strategies were evaluated from the societal perspective, comparing quality-adjusted life-years (QALYs) and cost per QALY. For both the primary and secondary analyses, sensitivity analyses were performed across a range of values for each input.

Main findings. Tranexamic acid use would be cost saving if the relative risk reduction for maternal death with TXA was greater than approximately 5%, which is significantly lower than that seen in the WOMAN trial (19%). The primary analysis demonstrated that—assuming a 3% rate of PPH—giving TXA to women with PPH would save $11.3 million, prevent 334 laparotomies, and avert 9 maternal deaths annually in the United States. This cost saving nearly tripled if TXA was administered within 3 hours of delivery, with 5 additional maternal deaths prevented.

Secondary analysis incorporating QALYs also showed TXA use to be cost-effective. These findings held through various sensitivity analyses.

Continue to: Study strengths and limitations...

Study strengths and limitations

This study is novel in its critical objective to determine the cost-effectiveness of routine use of TXA for PPH in the United States. Robust modeling using Monte Carlo estimation and a variety of sensitivity analyses add reliability to the authors’ findings.

This work is limited, however, by the assumptions put into the authors’ models. For example, outcome data regarding effectiveness of TXA was taken from the WOMAN trial, which was not performed within the United States. In addition, it is difficult to quantify in dollars an event as profound as a maternal death. The authors recognize that they likely underestimate the “cost” of a maternal death, but that this underestimation would only increase the cost-effectiveness of TXA.

Finally, it is important to take into account that such economic analyses are helpful to inform institutional guidelines and hemorrhage protocols, but that patient-specific decision-making should be individualized based on the clinical scenario at hand.

Case 1 Induction at 39 weeks in a healthy nulliparous woman

A healthy 35-year-old woman (G1P0) at 39 weeks 0 days and with an uncomplicated pregnancy presents to your office for a routine prenatal visit. She inquires about scheduling an induction of labor, noting that she read a news story about induction at 39 weeks and that it might lower her chance of having a cesarean delivery (CD).

You perform a cervical exam—she is 1 cm dilated, 3 cm long, -2 station, posterior, and firm. You sweep her membranes after obtaining verbal consent. After describing the induction process, you explain that she might be hospitalized for several days before the birth given the need for cervical ripening. “You mean I need to stay in the hospital for the entire process?” she asks incredulously.
 

Over the past 20 years, the percentage of patients undergoing induction of labor (IOL) has increased from 10% to 25%.¹ This percentage likely will rise over time, particularly in the wake of a recent randomized controlled trial suggesting potential maternal benefits, such as reduced CD rate, for nulliparas induced at 39 weeks compared with expectant management.² Although there have not been any changes to guidelines for timing of IOL from such professional societies such as the American College of Obstetricians and Gynecologists (ACOG) or the Society for Maternal-Fetal Medicine, key considerations of rising IOL volume include patient experience, labor and delivery (L&D) units’ capacity and resources, and associated health care costs.

An essential part of successful induction involves patience. Induction can be a lengthy process, particularly for nulliparas with unripe cervices. Cervical ripening is a necessary component of successful labor induction, whether achieved mechanically or pharmacologically with synthetic prostaglandins, and it has been shown to lower the chance of CD.^3,4 However, achieving a ripe cervix is often the lengthiest part of an induction, and not uncommonly consumes 12 to 24 hours or more of inpatient time. Investigators have sought ways to make this process more expeditious. For example, the FOR-MOMI trial demonstrated that the induction-to-delivery time was several hours shorter when cervical ripening combined mechanical and pharmacologic approaches (Foley balloon plus misoprostol), compared with either method alone, without any increase in maternal or fetal complication rates.⁵

Better yet, what if admission to the L&D unit for IOL at term could be deferred until the cervix is ripe? A number of hospitals in the United States have successfully introduced outpatient cervical ripening, and several small observational and randomized controlled trials have reported good results in terms of safety, efficacy and time saved, and patient experience. Here, we will make the case that outpatient cervical ripening should be the standard of care for low-risk pregnancies.

Mechanical cervical ripening

Safety

Although data are limited on the safety, the authors of an ACOG Practice Bulletin suggest that, based on the available evidence of mechanical ripening in an inpatient setting, it is also appropriate in the outpatient setting.⁶ Unlike cervical ripening using prostaglandins, mechanical ripening is not associated with tachysystole, fetal intolerance of labor, or meconium staining.³ A cohort study of nearly 2,000 low-risk patients who underwent Foley catheter placement for cervical ripening using an outpatient protocol but monitored overnight as inpatients and evaluated for adverse outcomes found no CD for fetal distress, vaginal bleeding, placental abruption, or intrapartum stillbirth.⁷ The authors posited that, given this safety profile in the inpatient setting, that mechanical cervical ripening with a Foley catheter would be appropriate for outpatient use in low-risk populations. Other systematic reviews have been reassuring as well, with exceedingly low complication rates during inpatient mechanical cervical ripening.⁸ These data advocate for the evaluation of cervical ripening in the outpatient setting.

The evidence for outpatient mechanical ripening, although again limited, also has demonstrated safety. There does not appear to be an increased rate of maternal or neonatal complications, including infectious morbidity, postpartum hemorrhage, CD, operative vaginal delivery, or fetal distress.^9-12

Continue to: Efficacy and length-of-stay...

Efficacy and length-of-stay

Efficacy also generally has been shown to be similar when mechanical methods are used in the inpatient and outpatient settings. Small randomized trials of outpatient versus inpatient Foley catheter ripening have shown decreased length of stay (by 10 to 13 hours) and similar or less oxytocin use in the outpatient groups, as well as similar Bishop scores after cervical ripening and no difference in maternal or fetal outcomes.^9,11,13,14

One major concern with increasing IOL prevalence is the availability of hospital resources and the associated health care costs, given the known increased length of inpatient stay due to cervical ripening time. Admission to an L&D unit is resource intensive; the costs are similar to admission to an intensive care unit in many hospitals given its level of acuity and high nurse/patient ratio. However, given the safety of outpatient mechanical cervical ripening described above, we argue that routinely admitting low-risk patients for mechanical ripening constitutes a suboptimal use of costly resources.

Indeed, data suggest significant inpatient time savings if cervical ripening can be accomplished prior to admission. A cost-effectiveness analysis in the Netherlands demonstrated a nearly 1,000-euro decrease in cost per induction when Foley catheter induction was done on an outpatient basis.¹⁵ Interestingly, a recent trial confined to multiparas found no differences in hospital time when comparing outpatient ripening with Foley balloon alone with inpatient ripening with Foley balloon plus simultaneous oxytocin.¹⁰ This certainly merits further study, but it may be that the largest time- and cost-savings are among nulliparas.

Patient preferences

Relatively few studies specifically have addressed patient experiences with outpatient versus inpatient mechanical cervical ripening. Outpatient cervical ripening may provide patients with the benefits of being in the comfort of their own homes with their preferred support persons, increased mobility, more bodily autonomy, and satisfaction with their birthing process.

In a pilot trial involving 48 women, inpatient was compared with outpatient cervical ripening using a Foley balloon. Those in the outpatient group reported getting more rest, feeling less isolated, and having enough privacy. However, participants in both groups were equally satisfied and equally likely to recommend their method of induction to others.¹¹ Another study comparing outpatient versus inpatient Foley balloon cervical ripening found that 85% of patients who underwent outpatient ripening were satisfied with the induction method; however, no query or comparison was done with the inpatient group.¹² A trial comparing outpatient mechanical cervical ripening with inpatient misoprostol found that outpatient participants reported several hours more sleep and less pain.¹⁶ And in a discrete choice experiment of British gravidas, participants favored the option of outpatient cervical ripening, even if it meant an extra 1.4 trips to the hospital and over an hour of extra travel time.¹⁷

While these preliminary findings provide some insight that patients may prefer an outpatient approach to cervical ripening, more studies are needed to fully evaluate patient desires.

Continue to: Our approach to mechanical cervical ripening...

Our approach to mechanical cervical ripening

Most patients undergoing scheduled IOL are reasonable candidates for outpatient cervical ripening based on safety and efficacy. By definition, scheduling in advance implies that the provider has determined that outpatient management is reasonable until that date, and the plan for outpatient ripening need not prolong this period.

FIGURES 1 and 2 show protocols for our 2 hospital centers, which regularly allow for outpatient mechanical cervical ripening. In the process of protocol development, we identified absolute and relative contraindications to determine appropriate candidates. We exclude women who require inpatient management of medical or obstetric conditions (for example, women with severe preeclampsia or any condition requiring continuous fetal monitoring). We also do not routinely recommend outpatient cervical ripening to patients who do not have the necessary social conditions to make this process as safe as possible (including stable housing, reliable transportation, and a support person), although this occurs with some exceptions depending on individual patient situations.

Some examples of ideal candidates for outpatient mechanical cervical ripening include those undergoing elective or routine prolonged gestation inductions, or inductions for well-controlled, stable conditions (chronic hypertension and gestational diabetes). At one center, after thorough counseling and assessment, outpatient cervical ripening is also offered to patients with mild risk factors, including twins, prior low transverse CD, stable preeclampsia without severe features, isolated oligohydramnios with otherwise reassuring fetal status, and other similar conditions.

After mechanical cervical ripening placement (either Foley catheter or mechanical dilators), the clinician completes a postprocedure safety checklist and detailed procedure documentation, including number and type of foreign bodies placed. If there are any concerns regarding maternal or fetal well-being, the patient is sent to L&D for evaluation. If the procedure was tolerated well, the patient is discharged home, after a reactive postprocedure nonstress test is done, with detailed instructions for self-care, as well as with a list of symptoms that warrant prompt evaluation prior to scheduled induction time. In a large California hospital group following a similar protocol, only about 5% of women presented in labor before their scheduled induction.¹⁸

Case 2 Cervical ripening for labor preparation in low-risk pregnancy

A 32-year-old woman (G1P0) with an uncomplicated pregnancy at 40 weeks and 3 days presents to your office for a routine prenatal visit. Her vital signs are normal, and her fetus is vertex with an estimated fetal weight of 7.5 lb by Leopald’s maneuvers. You perform a cervical exam and find that her cervix is closed, long, and posterior.

You discuss with her your recommendation for induction of labor by 41 weeks, and she agrees. You also discuss the need for cervical ripening and recommend misoprostol given her closed cervix. You explain that several doses may be needed to get her cervix ready for labor, and she asks, “Do I have to stay in the hospital that whole time?”

Pharmacologic cervical ripening

Efficacy

There are multiple pharmacologic agents that can be used for ripening an unfavorable cervix. The main agents used in the United States are prostaglandins, either PGE1 (oral or vaginal misoprostol) or PGE2 in a gel or sustained-release vaginal insert (dinoprostone).

Outpatient misoprostol to avoid labor induction. Many studies have looked at outpatient misoprostol use as a “prophylactic measure” (to prevent the need for labor induction). For example, Gaffaney and colleagues showed that administering outpatient oral misoprostol (100 µg every 24 hours for up to 3 doses) after 40 weeks’ gestation to women with an unfavorable cervix significantly decreased the time to delivery by a day and a half.¹⁹ Similarly, PonMalar and colleagues demonstrated that administering 25 µg of vaginal misoprostol in a single dose as an outpatient after stripping the membranes significantly reduced time to delivery by 2 days.²⁰ And Stitely and colleagues found a significant reduction in the need for labor induction with the use of outpatient vaginal misoprostol. They administered up to 2 doses of misoprostol 25 µg vaginally every 24 hours for the 48 hours prior to a scheduled postdates induction and found a large reduction in the need for labor induction (11% vs 85%; P<.01).²¹

Continue to: Multiple protocols and regimens...

Multiple protocols and regimens have been studied but, overall, the findings suggest that administering outpatient misoprostol may shorten the time interval to spontaneous labor and decrease the need for a formal labor induction.^19-23

Inpatient compared with outpatient prostaglandin use. These trials of “prophylactic” misoprostol generally have compared outpatient administration of misoprostol with placebo. Prostaglandins are one of the most common methods of inpatient cervical ripening, so what about comparisons of inpatient cervical ripening with outpatient prostaglandin administration? There are a handful of studies that make this comparison.

Chang and colleagues looked retrospectively at inpatient and outpatient misoprostol and found that outpatient administration saved 3 to 5 hours on labor and delivery.²⁴ Biem and colleagues randomly assigned women to either inpatient cervical ripening with PGE2 intravaginal inserts or 1 hour of inpatient monitoring after PGE2 administration and then outpatient discharge until the onset of labor or for a nonstress test at 12 hours. They found that those who underwent outpatient ripening spent 8 hours less on labor and delivery and were more highly satisfied with the initial 12 hours of labor induction experience (56% vs 39%; P<.01).²⁵

The largest randomized controlled trial conducted to study outpatient prostaglandin use was the OPRA study (involving 827 women). Investigators compared inpatient to outpatient PGE2 intravaginal gel.²⁶ The primary outcome was total oxytocin administration, which was not different between groups. The study was underpowered, however, as 50% of women labored spontaneously postrandomization. But in the outpatient arm, less than half of the women required additional inpatient ripening, and nearly 40% returned in spontaneous labor, suggesting that outpatient prostaglandin administration may indeed save women a significant amount of time on labor and delivery.

Safety

The safety of outpatient administration of prostaglandins is the biggest concern, especially since, when prostaglandins are compared to outpatient Foley catheter use, Foleys are overall associated with less tachysystole, fetal intolerance, and meconium-stained fluid.³ Foley catheter use for cervical ripening may not be an appropriate choice for all patients, however. For instance, our case patient has a closed cervix, which could make Foley insertion uncomfortable or even impossible. Misoprostol use also offers the potential for flexibility in cervical ripening protocols as patients need not return for Foley balloon removal and indeed labor induction need not take place immediately after administration of misoprostol.

Patients also may prefer outpatient cervical ripening with misoprostol over a Foley. There are some data to suggest that women, overall, have a preference toward prostaglandins; in the PROBAAT-II trial, which compared inpatient oral misoprostol to Foley catheter for cervical ripening, 12% of women in the Foley arm would have preferred another method of induction (vs 6% in the misoprostol arm; P = .02).²⁷ This preference may be magnified in an outpatient setting.

But, again, is outpatient administration of prostaglandins safe? The published trials thus far have not reported an increase in out-of-hospital deliveries or adverse fetal outcomes. However, studies have been of limited size to see more rare outcomes. Unfortunately, an adequately powered study to demonstrate safety is likely never to be accomplished, given that if used responsibly (in low-risk patients with adequate monitoring after administration) the incidence of adverse fetal outcomes during the at-home portion of cervical ripening is likely to be very low. With responsible use, outpatient administration of prostaglandins should be safe. Women are monitored after misoprostol administration and are not sent home if there are any concerns for fetal distress or if frequent contractions continue. Misoprostol reaches maximum blood concentration 30 minutes after oral administration and 70 to 80 minutes after vaginal administration.²⁸ After this time, if contractions start to intensify it is likely that misoprostol has triggered spontaneous labor. In this setting, women are routinely allowed to spontaneously labor at home. One may even argue that outpatient misoprostol could lead to improved safety, as women essentially have a contraction stress test prior to spontaneous labor, and misoprostol administration as an outpatient, as opposed to as an inpatient, may allow for longer time intervals between doses, which could prevent dose stacking.

Continue to: Our approach to pharmacologic cervical ripening...

Our approach to pharmacologic cervical ripening

Our hospital has been conducting outpatient cervical ripening using vaginal misoprostol for more than 15 years without any known adverse safety concerns (FIGURE 3). Women with a low-risk, singleton pregnancy between 39+0 and 40+6 weeks are potential candidates for outpatient ripening. The majority of outpatient inductions are done electively without any medical indication. Women with stable, minor risk factors (such as diet-controlled gestational diabetes) also may be candidates at their clinician’s discretion. Patients are monitored either in our L&D triage area or in our outpatient antenatal unit; both units are in the same building. One clinician offers outpatient misoprostol in the office, across the street from L&D. We allow for clinician flexibility after administration. Some clinicians do 1 or 2 doses of outpatient cervical ripening in a day prior to a scheduled inpatient induction the next day. Some do multiple daily doses over the course of a week.

Conclusion

While the data continue to be limited, we strongly believe there is sufficient quality evidence from a safety and efficacy perspective to support implementation and evaluation of outpatient cervical ripening protocols for low-risk pregnancies. In the setting of renewed commitments to reducing suboptimal health care costs and utilization as well as increasing patient satisfaction and control in their birthing experiences, we posit it is the responsibility of obstetricians, L&D leadership, and health care institutions to explore the implementation of outpatient cervical ripening for appropriate candidates in their settings.

Case 1 Induction at 39 weeks in a healthy nulliparous woman

A healthy 35-year-old woman (G1P0) at 39 weeks 0 days and with an uncomplicated pregnancy presents to your office for a routine prenatal visit. She inquires about scheduling an induction of labor, noting that she read a news story about induction at 39 weeks and that it might lower her chance of having a cesarean delivery (CD).

You perform a cervical exam—she is 1 cm dilated, 3 cm long, -2 station, posterior, and firm. You sweep her membranes after obtaining verbal consent. After describing the induction process, you explain that she might be hospitalized for several days before the birth given the need for cervical ripening. “You mean I need to stay in the hospital for the entire process?” she asks incredulously.
 

Over the past 20 years, the percentage of patients undergoing induction of labor (IOL) has increased from 10% to 25%.¹ This percentage likely will rise over time, particularly in the wake of a recent randomized controlled trial suggesting potential maternal benefits, such as reduced CD rate, for nulliparas induced at 39 weeks compared with expectant management.² Although there have not been any changes to guidelines for timing of IOL from such professional societies such as the American College of Obstetricians and Gynecologists (ACOG) or the Society for Maternal-Fetal Medicine, key considerations of rising IOL volume include patient experience, labor and delivery (L&D) units’ capacity and resources, and associated health care costs.

An essential part of successful induction involves patience. Induction can be a lengthy process, particularly for nulliparas with unripe cervices. Cervical ripening is a necessary component of successful labor induction, whether achieved mechanically or pharmacologically with synthetic prostaglandins, and it has been shown to lower the chance of CD.^3,4 However, achieving a ripe cervix is often the lengthiest part of an induction, and not uncommonly consumes 12 to 24 hours or more of inpatient time. Investigators have sought ways to make this process more expeditious. For example, the FOR-MOMI trial demonstrated that the induction-to-delivery time was several hours shorter when cervical ripening combined mechanical and pharmacologic approaches (Foley balloon plus misoprostol), compared with either method alone, without any increase in maternal or fetal complication rates.⁵

Better yet, what if admission to the L&D unit for IOL at term could be deferred until the cervix is ripe? A number of hospitals in the United States have successfully introduced outpatient cervical ripening, and several small observational and randomized controlled trials have reported good results in terms of safety, efficacy and time saved, and patient experience. Here, we will make the case that outpatient cervical ripening should be the standard of care for low-risk pregnancies.

Mechanical cervical ripening

Safety

Although data are limited on the safety, the authors of an ACOG Practice Bulletin suggest that, based on the available evidence of mechanical ripening in an inpatient setting, it is also appropriate in the outpatient setting.⁶ Unlike cervical ripening using prostaglandins, mechanical ripening is not associated with tachysystole, fetal intolerance of labor, or meconium staining.³ A cohort study of nearly 2,000 low-risk patients who underwent Foley catheter placement for cervical ripening using an outpatient protocol but monitored overnight as inpatients and evaluated for adverse outcomes found no CD for fetal distress, vaginal bleeding, placental abruption, or intrapartum stillbirth.⁷ The authors posited that, given this safety profile in the inpatient setting, that mechanical cervical ripening with a Foley catheter would be appropriate for outpatient use in low-risk populations. Other systematic reviews have been reassuring as well, with exceedingly low complication rates during inpatient mechanical cervical ripening.⁸ These data advocate for the evaluation of cervical ripening in the outpatient setting.

The evidence for outpatient mechanical ripening, although again limited, also has demonstrated safety. There does not appear to be an increased rate of maternal or neonatal complications, including infectious morbidity, postpartum hemorrhage, CD, operative vaginal delivery, or fetal distress.^9-12

Continue to: Efficacy and length-of-stay...

Efficacy and length-of-stay

Efficacy also generally has been shown to be similar when mechanical methods are used in the inpatient and outpatient settings. Small randomized trials of outpatient versus inpatient Foley catheter ripening have shown decreased length of stay (by 10 to 13 hours) and similar or less oxytocin use in the outpatient groups, as well as similar Bishop scores after cervical ripening and no difference in maternal or fetal outcomes.^9,11,13,14

One major concern with increasing IOL prevalence is the availability of hospital resources and the associated health care costs, given the known increased length of inpatient stay due to cervical ripening time. Admission to an L&D unit is resource intensive; the costs are similar to admission to an intensive care unit in many hospitals given its level of acuity and high nurse/patient ratio. However, given the safety of outpatient mechanical cervical ripening described above, we argue that routinely admitting low-risk patients for mechanical ripening constitutes a suboptimal use of costly resources.

Indeed, data suggest significant inpatient time savings if cervical ripening can be accomplished prior to admission. A cost-effectiveness analysis in the Netherlands demonstrated a nearly 1,000-euro decrease in cost per induction when Foley catheter induction was done on an outpatient basis.¹⁵ Interestingly, a recent trial confined to multiparas found no differences in hospital time when comparing outpatient ripening with Foley balloon alone with inpatient ripening with Foley balloon plus simultaneous oxytocin.¹⁰ This certainly merits further study, but it may be that the largest time- and cost-savings are among nulliparas.

Patient preferences

Relatively few studies specifically have addressed patient experiences with outpatient versus inpatient mechanical cervical ripening. Outpatient cervical ripening may provide patients with the benefits of being in the comfort of their own homes with their preferred support persons, increased mobility, more bodily autonomy, and satisfaction with their birthing process.

In a pilot trial involving 48 women, inpatient was compared with outpatient cervical ripening using a Foley balloon. Those in the outpatient group reported getting more rest, feeling less isolated, and having enough privacy. However, participants in both groups were equally satisfied and equally likely to recommend their method of induction to others.¹¹ Another study comparing outpatient versus inpatient Foley balloon cervical ripening found that 85% of patients who underwent outpatient ripening were satisfied with the induction method; however, no query or comparison was done with the inpatient group.¹² A trial comparing outpatient mechanical cervical ripening with inpatient misoprostol found that outpatient participants reported several hours more sleep and less pain.¹⁶ And in a discrete choice experiment of British gravidas, participants favored the option of outpatient cervical ripening, even if it meant an extra 1.4 trips to the hospital and over an hour of extra travel time.¹⁷

While these preliminary findings provide some insight that patients may prefer an outpatient approach to cervical ripening, more studies are needed to fully evaluate patient desires.

Continue to: Our approach to mechanical cervical ripening...

Our approach to mechanical cervical ripening

Most patients undergoing scheduled IOL are reasonable candidates for outpatient cervical ripening based on safety and efficacy. By definition, scheduling in advance implies that the provider has determined that outpatient management is reasonable until that date, and the plan for outpatient ripening need not prolong this period.

FIGURES 1 and 2 show protocols for our 2 hospital centers, which regularly allow for outpatient mechanical cervical ripening. In the process of protocol development, we identified absolute and relative contraindications to determine appropriate candidates. We exclude women who require inpatient management of medical or obstetric conditions (for example, women with severe preeclampsia or any condition requiring continuous fetal monitoring). We also do not routinely recommend outpatient cervical ripening to patients who do not have the necessary social conditions to make this process as safe as possible (including stable housing, reliable transportation, and a support person), although this occurs with some exceptions depending on individual patient situations.

Some examples of ideal candidates for outpatient mechanical cervical ripening include those undergoing elective or routine prolonged gestation inductions, or inductions for well-controlled, stable conditions (chronic hypertension and gestational diabetes). At one center, after thorough counseling and assessment, outpatient cervical ripening is also offered to patients with mild risk factors, including twins, prior low transverse CD, stable preeclampsia without severe features, isolated oligohydramnios with otherwise reassuring fetal status, and other similar conditions.

After mechanical cervical ripening placement (either Foley catheter or mechanical dilators), the clinician completes a postprocedure safety checklist and detailed procedure documentation, including number and type of foreign bodies placed. If there are any concerns regarding maternal or fetal well-being, the patient is sent to L&D for evaluation. If the procedure was tolerated well, the patient is discharged home, after a reactive postprocedure nonstress test is done, with detailed instructions for self-care, as well as with a list of symptoms that warrant prompt evaluation prior to scheduled induction time. In a large California hospital group following a similar protocol, only about 5% of women presented in labor before their scheduled induction.¹⁸

Case 2 Cervical ripening for labor preparation in low-risk pregnancy

A 32-year-old woman (G1P0) with an uncomplicated pregnancy at 40 weeks and 3 days presents to your office for a routine prenatal visit. Her vital signs are normal, and her fetus is vertex with an estimated fetal weight of 7.5 lb by Leopald’s maneuvers. You perform a cervical exam and find that her cervix is closed, long, and posterior.

You discuss with her your recommendation for induction of labor by 41 weeks, and she agrees. You also discuss the need for cervical ripening and recommend misoprostol given her closed cervix. You explain that several doses may be needed to get her cervix ready for labor, and she asks, “Do I have to stay in the hospital that whole time?”

Pharmacologic cervical ripening

Efficacy

There are multiple pharmacologic agents that can be used for ripening an unfavorable cervix. The main agents used in the United States are prostaglandins, either PGE1 (oral or vaginal misoprostol) or PGE2 in a gel or sustained-release vaginal insert (dinoprostone).

Outpatient misoprostol to avoid labor induction. Many studies have looked at outpatient misoprostol use as a “prophylactic measure” (to prevent the need for labor induction). For example, Gaffaney and colleagues showed that administering outpatient oral misoprostol (100 µg every 24 hours for up to 3 doses) after 40 weeks’ gestation to women with an unfavorable cervix significantly decreased the time to delivery by a day and a half.¹⁹ Similarly, PonMalar and colleagues demonstrated that administering 25 µg of vaginal misoprostol in a single dose as an outpatient after stripping the membranes significantly reduced time to delivery by 2 days.²⁰ And Stitely and colleagues found a significant reduction in the need for labor induction with the use of outpatient vaginal misoprostol. They administered up to 2 doses of misoprostol 25 µg vaginally every 24 hours for the 48 hours prior to a scheduled postdates induction and found a large reduction in the need for labor induction (11% vs 85%; P<.01).²¹

Continue to: Multiple protocols and regimens...

Multiple protocols and regimens have been studied but, overall, the findings suggest that administering outpatient misoprostol may shorten the time interval to spontaneous labor and decrease the need for a formal labor induction.^19-23

Inpatient compared with outpatient prostaglandin use. These trials of “prophylactic” misoprostol generally have compared outpatient administration of misoprostol with placebo. Prostaglandins are one of the most common methods of inpatient cervical ripening, so what about comparisons of inpatient cervical ripening with outpatient prostaglandin administration? There are a handful of studies that make this comparison.

Chang and colleagues looked retrospectively at inpatient and outpatient misoprostol and found that outpatient administration saved 3 to 5 hours on labor and delivery.²⁴ Biem and colleagues randomly assigned women to either inpatient cervical ripening with PGE2 intravaginal inserts or 1 hour of inpatient monitoring after PGE2 administration and then outpatient discharge until the onset of labor or for a nonstress test at 12 hours. They found that those who underwent outpatient ripening spent 8 hours less on labor and delivery and were more highly satisfied with the initial 12 hours of labor induction experience (56% vs 39%; P<.01).²⁵

The largest randomized controlled trial conducted to study outpatient prostaglandin use was the OPRA study (involving 827 women). Investigators compared inpatient to outpatient PGE2 intravaginal gel.²⁶ The primary outcome was total oxytocin administration, which was not different between groups. The study was underpowered, however, as 50% of women labored spontaneously postrandomization. But in the outpatient arm, less than half of the women required additional inpatient ripening, and nearly 40% returned in spontaneous labor, suggesting that outpatient prostaglandin administration may indeed save women a significant amount of time on labor and delivery.

Safety

The safety of outpatient administration of prostaglandins is the biggest concern, especially since, when prostaglandins are compared to outpatient Foley catheter use, Foleys are overall associated with less tachysystole, fetal intolerance, and meconium-stained fluid.³ Foley catheter use for cervical ripening may not be an appropriate choice for all patients, however. For instance, our case patient has a closed cervix, which could make Foley insertion uncomfortable or even impossible. Misoprostol use also offers the potential for flexibility in cervical ripening protocols as patients need not return for Foley balloon removal and indeed labor induction need not take place immediately after administration of misoprostol.

Patients also may prefer outpatient cervical ripening with misoprostol over a Foley. There are some data to suggest that women, overall, have a preference toward prostaglandins; in the PROBAAT-II trial, which compared inpatient oral misoprostol to Foley catheter for cervical ripening, 12% of women in the Foley arm would have preferred another method of induction (vs 6% in the misoprostol arm; P = .02).²⁷ This preference may be magnified in an outpatient setting.

But, again, is outpatient administration of prostaglandins safe? The published trials thus far have not reported an increase in out-of-hospital deliveries or adverse fetal outcomes. However, studies have been of limited size to see more rare outcomes. Unfortunately, an adequately powered study to demonstrate safety is likely never to be accomplished, given that if used responsibly (in low-risk patients with adequate monitoring after administration) the incidence of adverse fetal outcomes during the at-home portion of cervical ripening is likely to be very low. With responsible use, outpatient administration of prostaglandins should be safe. Women are monitored after misoprostol administration and are not sent home if there are any concerns for fetal distress or if frequent contractions continue. Misoprostol reaches maximum blood concentration 30 minutes after oral administration and 70 to 80 minutes after vaginal administration.²⁸ After this time, if contractions start to intensify it is likely that misoprostol has triggered spontaneous labor. In this setting, women are routinely allowed to spontaneously labor at home. One may even argue that outpatient misoprostol could lead to improved safety, as women essentially have a contraction stress test prior to spontaneous labor, and misoprostol administration as an outpatient, as opposed to as an inpatient, may allow for longer time intervals between doses, which could prevent dose stacking.

Continue to: Our approach to pharmacologic cervical ripening...

Our approach to pharmacologic cervical ripening

Our hospital has been conducting outpatient cervical ripening using vaginal misoprostol for more than 15 years without any known adverse safety concerns (FIGURE 3). Women with a low-risk, singleton pregnancy between 39+0 and 40+6 weeks are potential candidates for outpatient ripening. The majority of outpatient inductions are done electively without any medical indication. Women with stable, minor risk factors (such as diet-controlled gestational diabetes) also may be candidates at their clinician’s discretion. Patients are monitored either in our L&D triage area or in our outpatient antenatal unit; both units are in the same building. One clinician offers outpatient misoprostol in the office, across the street from L&D. We allow for clinician flexibility after administration. Some clinicians do 1 or 2 doses of outpatient cervical ripening in a day prior to a scheduled inpatient induction the next day. Some do multiple daily doses over the course of a week.

Conclusion

While the data continue to be limited, we strongly believe there is sufficient quality evidence from a safety and efficacy perspective to support implementation and evaluation of outpatient cervical ripening protocols for low-risk pregnancies. In the setting of renewed commitments to reducing suboptimal health care costs and utilization as well as increasing patient satisfaction and control in their birthing experiences, we posit it is the responsibility of obstetricians, L&D leadership, and health care institutions to explore the implementation of outpatient cervical ripening for appropriate candidates in their settings.

Case 1 Induction at 39 weeks in a healthy nulliparous woman

A healthy 35-year-old woman (G1P0) at 39 weeks 0 days and with an uncomplicated pregnancy presents to your office for a routine prenatal visit. She inquires about scheduling an induction of labor, noting that she read a news story about induction at 39 weeks and that it might lower her chance of having a cesarean delivery (CD).

You perform a cervical exam—she is 1 cm dilated, 3 cm long, -2 station, posterior, and firm. You sweep her membranes after obtaining verbal consent. After describing the induction process, you explain that she might be hospitalized for several days before the birth given the need for cervical ripening. “You mean I need to stay in the hospital for the entire process?” she asks incredulously.
 

Over the past 20 years, the percentage of patients undergoing induction of labor (IOL) has increased from 10% to 25%.¹ This percentage likely will rise over time, particularly in the wake of a recent randomized controlled trial suggesting potential maternal benefits, such as reduced CD rate, for nulliparas induced at 39 weeks compared with expectant management.² Although there have not been any changes to guidelines for timing of IOL from such professional societies such as the American College of Obstetricians and Gynecologists (ACOG) or the Society for Maternal-Fetal Medicine, key considerations of rising IOL volume include patient experience, labor and delivery (L&D) units’ capacity and resources, and associated health care costs.

An essential part of successful induction involves patience. Induction can be a lengthy process, particularly for nulliparas with unripe cervices. Cervical ripening is a necessary component of successful labor induction, whether achieved mechanically or pharmacologically with synthetic prostaglandins, and it has been shown to lower the chance of CD.^3,4 However, achieving a ripe cervix is often the lengthiest part of an induction, and not uncommonly consumes 12 to 24 hours or more of inpatient time. Investigators have sought ways to make this process more expeditious. For example, the FOR-MOMI trial demonstrated that the induction-to-delivery time was several hours shorter when cervical ripening combined mechanical and pharmacologic approaches (Foley balloon plus misoprostol), compared with either method alone, without any increase in maternal or fetal complication rates.⁵

Better yet, what if admission to the L&D unit for IOL at term could be deferred until the cervix is ripe? A number of hospitals in the United States have successfully introduced outpatient cervical ripening, and several small observational and randomized controlled trials have reported good results in terms of safety, efficacy and time saved, and patient experience. Here, we will make the case that outpatient cervical ripening should be the standard of care for low-risk pregnancies.

Mechanical cervical ripening

Safety

Although data are limited on the safety, the authors of an ACOG Practice Bulletin suggest that, based on the available evidence of mechanical ripening in an inpatient setting, it is also appropriate in the outpatient setting.⁶ Unlike cervical ripening using prostaglandins, mechanical ripening is not associated with tachysystole, fetal intolerance of labor, or meconium staining.³ A cohort study of nearly 2,000 low-risk patients who underwent Foley catheter placement for cervical ripening using an outpatient protocol but monitored overnight as inpatients and evaluated for adverse outcomes found no CD for fetal distress, vaginal bleeding, placental abruption, or intrapartum stillbirth.⁷ The authors posited that, given this safety profile in the inpatient setting, that mechanical cervical ripening with a Foley catheter would be appropriate for outpatient use in low-risk populations. Other systematic reviews have been reassuring as well, with exceedingly low complication rates during inpatient mechanical cervical ripening.⁸ These data advocate for the evaluation of cervical ripening in the outpatient setting.

The evidence for outpatient mechanical ripening, although again limited, also has demonstrated safety. There does not appear to be an increased rate of maternal or neonatal complications, including infectious morbidity, postpartum hemorrhage, CD, operative vaginal delivery, or fetal distress.^9-12

Continue to: Efficacy and length-of-stay...

Efficacy and length-of-stay

Efficacy also generally has been shown to be similar when mechanical methods are used in the inpatient and outpatient settings. Small randomized trials of outpatient versus inpatient Foley catheter ripening have shown decreased length of stay (by 10 to 13 hours) and similar or less oxytocin use in the outpatient groups, as well as similar Bishop scores after cervical ripening and no difference in maternal or fetal outcomes.^9,11,13,14

One major concern with increasing IOL prevalence is the availability of hospital resources and the associated health care costs, given the known increased length of inpatient stay due to cervical ripening time. Admission to an L&D unit is resource intensive; the costs are similar to admission to an intensive care unit in many hospitals given its level of acuity and high nurse/patient ratio. However, given the safety of outpatient mechanical cervical ripening described above, we argue that routinely admitting low-risk patients for mechanical ripening constitutes a suboptimal use of costly resources.

Indeed, data suggest significant inpatient time savings if cervical ripening can be accomplished prior to admission. A cost-effectiveness analysis in the Netherlands demonstrated a nearly 1,000-euro decrease in cost per induction when Foley catheter induction was done on an outpatient basis.¹⁵ Interestingly, a recent trial confined to multiparas found no differences in hospital time when comparing outpatient ripening with Foley balloon alone with inpatient ripening with Foley balloon plus simultaneous oxytocin.¹⁰ This certainly merits further study, but it may be that the largest time- and cost-savings are among nulliparas.

Patient preferences

Relatively few studies specifically have addressed patient experiences with outpatient versus inpatient mechanical cervical ripening. Outpatient cervical ripening may provide patients with the benefits of being in the comfort of their own homes with their preferred support persons, increased mobility, more bodily autonomy, and satisfaction with their birthing process.

In a pilot trial involving 48 women, inpatient was compared with outpatient cervical ripening using a Foley balloon. Those in the outpatient group reported getting more rest, feeling less isolated, and having enough privacy. However, participants in both groups were equally satisfied and equally likely to recommend their method of induction to others.¹¹ Another study comparing outpatient versus inpatient Foley balloon cervical ripening found that 85% of patients who underwent outpatient ripening were satisfied with the induction method; however, no query or comparison was done with the inpatient group.¹² A trial comparing outpatient mechanical cervical ripening with inpatient misoprostol found that outpatient participants reported several hours more sleep and less pain.¹⁶ And in a discrete choice experiment of British gravidas, participants favored the option of outpatient cervical ripening, even if it meant an extra 1.4 trips to the hospital and over an hour of extra travel time.¹⁷

While these preliminary findings provide some insight that patients may prefer an outpatient approach to cervical ripening, more studies are needed to fully evaluate patient desires.

Continue to: Our approach to mechanical cervical ripening...

Our approach to mechanical cervical ripening

Most patients undergoing scheduled IOL are reasonable candidates for outpatient cervical ripening based on safety and efficacy. By definition, scheduling in advance implies that the provider has determined that outpatient management is reasonable until that date, and the plan for outpatient ripening need not prolong this period.

FIGURES 1 and 2 show protocols for our 2 hospital centers, which regularly allow for outpatient mechanical cervical ripening. In the process of protocol development, we identified absolute and relative contraindications to determine appropriate candidates. We exclude women who require inpatient management of medical or obstetric conditions (for example, women with severe preeclampsia or any condition requiring continuous fetal monitoring). We also do not routinely recommend outpatient cervical ripening to patients who do not have the necessary social conditions to make this process as safe as possible (including stable housing, reliable transportation, and a support person), although this occurs with some exceptions depending on individual patient situations.

Some examples of ideal candidates for outpatient mechanical cervical ripening include those undergoing elective or routine prolonged gestation inductions, or inductions for well-controlled, stable conditions (chronic hypertension and gestational diabetes). At one center, after thorough counseling and assessment, outpatient cervical ripening is also offered to patients with mild risk factors, including twins, prior low transverse CD, stable preeclampsia without severe features, isolated oligohydramnios with otherwise reassuring fetal status, and other similar conditions.

After mechanical cervical ripening placement (either Foley catheter or mechanical dilators), the clinician completes a postprocedure safety checklist and detailed procedure documentation, including number and type of foreign bodies placed. If there are any concerns regarding maternal or fetal well-being, the patient is sent to L&D for evaluation. If the procedure was tolerated well, the patient is discharged home, after a reactive postprocedure nonstress test is done, with detailed instructions for self-care, as well as with a list of symptoms that warrant prompt evaluation prior to scheduled induction time. In a large California hospital group following a similar protocol, only about 5% of women presented in labor before their scheduled induction.¹⁸

Case 2 Cervical ripening for labor preparation in low-risk pregnancy

A 32-year-old woman (G1P0) with an uncomplicated pregnancy at 40 weeks and 3 days presents to your office for a routine prenatal visit. Her vital signs are normal, and her fetus is vertex with an estimated fetal weight of 7.5 lb by Leopald’s maneuvers. You perform a cervical exam and find that her cervix is closed, long, and posterior.

You discuss with her your recommendation for induction of labor by 41 weeks, and she agrees. You also discuss the need for cervical ripening and recommend misoprostol given her closed cervix. You explain that several doses may be needed to get her cervix ready for labor, and she asks, “Do I have to stay in the hospital that whole time?”

Pharmacologic cervical ripening

Efficacy

There are multiple pharmacologic agents that can be used for ripening an unfavorable cervix. The main agents used in the United States are prostaglandins, either PGE1 (oral or vaginal misoprostol) or PGE2 in a gel or sustained-release vaginal insert (dinoprostone).

Outpatient misoprostol to avoid labor induction. Many studies have looked at outpatient misoprostol use as a “prophylactic measure” (to prevent the need for labor induction). For example, Gaffaney and colleagues showed that administering outpatient oral misoprostol (100 µg every 24 hours for up to 3 doses) after 40 weeks’ gestation to women with an unfavorable cervix significantly decreased the time to delivery by a day and a half.¹⁹ Similarly, PonMalar and colleagues demonstrated that administering 25 µg of vaginal misoprostol in a single dose as an outpatient after stripping the membranes significantly reduced time to delivery by 2 days.²⁰ And Stitely and colleagues found a significant reduction in the need for labor induction with the use of outpatient vaginal misoprostol. They administered up to 2 doses of misoprostol 25 µg vaginally every 24 hours for the 48 hours prior to a scheduled postdates induction and found a large reduction in the need for labor induction (11% vs 85%; P<.01).²¹

Continue to: Multiple protocols and regimens...

Multiple protocols and regimens have been studied but, overall, the findings suggest that administering outpatient misoprostol may shorten the time interval to spontaneous labor and decrease the need for a formal labor induction.^19-23

Inpatient compared with outpatient prostaglandin use. These trials of “prophylactic” misoprostol generally have compared outpatient administration of misoprostol with placebo. Prostaglandins are one of the most common methods of inpatient cervical ripening, so what about comparisons of inpatient cervical ripening with outpatient prostaglandin administration? There are a handful of studies that make this comparison.

Chang and colleagues looked retrospectively at inpatient and outpatient misoprostol and found that outpatient administration saved 3 to 5 hours on labor and delivery.²⁴ Biem and colleagues randomly assigned women to either inpatient cervical ripening with PGE2 intravaginal inserts or 1 hour of inpatient monitoring after PGE2 administration and then outpatient discharge until the onset of labor or for a nonstress test at 12 hours. They found that those who underwent outpatient ripening spent 8 hours less on labor and delivery and were more highly satisfied with the initial 12 hours of labor induction experience (56% vs 39%; P<.01).²⁵

The largest randomized controlled trial conducted to study outpatient prostaglandin use was the OPRA study (involving 827 women). Investigators compared inpatient to outpatient PGE2 intravaginal gel.²⁶ The primary outcome was total oxytocin administration, which was not different between groups. The study was underpowered, however, as 50% of women labored spontaneously postrandomization. But in the outpatient arm, less than half of the women required additional inpatient ripening, and nearly 40% returned in spontaneous labor, suggesting that outpatient prostaglandin administration may indeed save women a significant amount of time on labor and delivery.

Safety

The safety of outpatient administration of prostaglandins is the biggest concern, especially since, when prostaglandins are compared to outpatient Foley catheter use, Foleys are overall associated with less tachysystole, fetal intolerance, and meconium-stained fluid.³ Foley catheter use for cervical ripening may not be an appropriate choice for all patients, however. For instance, our case patient has a closed cervix, which could make Foley insertion uncomfortable or even impossible. Misoprostol use also offers the potential for flexibility in cervical ripening protocols as patients need not return for Foley balloon removal and indeed labor induction need not take place immediately after administration of misoprostol.

Patients also may prefer outpatient cervical ripening with misoprostol over a Foley. There are some data to suggest that women, overall, have a preference toward prostaglandins; in the PROBAAT-II trial, which compared inpatient oral misoprostol to Foley catheter for cervical ripening, 12% of women in the Foley arm would have preferred another method of induction (vs 6% in the misoprostol arm; P = .02).²⁷ This preference may be magnified in an outpatient setting.

But, again, is outpatient administration of prostaglandins safe? The published trials thus far have not reported an increase in out-of-hospital deliveries or adverse fetal outcomes. However, studies have been of limited size to see more rare outcomes. Unfortunately, an adequately powered study to demonstrate safety is likely never to be accomplished, given that if used responsibly (in low-risk patients with adequate monitoring after administration) the incidence of adverse fetal outcomes during the at-home portion of cervical ripening is likely to be very low. With responsible use, outpatient administration of prostaglandins should be safe. Women are monitored after misoprostol administration and are not sent home if there are any concerns for fetal distress or if frequent contractions continue. Misoprostol reaches maximum blood concentration 30 minutes after oral administration and 70 to 80 minutes after vaginal administration.²⁸ After this time, if contractions start to intensify it is likely that misoprostol has triggered spontaneous labor. In this setting, women are routinely allowed to spontaneously labor at home. One may even argue that outpatient misoprostol could lead to improved safety, as women essentially have a contraction stress test prior to spontaneous labor, and misoprostol administration as an outpatient, as opposed to as an inpatient, may allow for longer time intervals between doses, which could prevent dose stacking.

Continue to: Our approach to pharmacologic cervical ripening...

Our approach to pharmacologic cervical ripening

Our hospital has been conducting outpatient cervical ripening using vaginal misoprostol for more than 15 years without any known adverse safety concerns (FIGURE 3). Women with a low-risk, singleton pregnancy between 39+0 and 40+6 weeks are potential candidates for outpatient ripening. The majority of outpatient inductions are done electively without any medical indication. Women with stable, minor risk factors (such as diet-controlled gestational diabetes) also may be candidates at their clinician’s discretion. Patients are monitored either in our L&D triage area or in our outpatient antenatal unit; both units are in the same building. One clinician offers outpatient misoprostol in the office, across the street from L&D. We allow for clinician flexibility after administration. Some clinicians do 1 or 2 doses of outpatient cervical ripening in a day prior to a scheduled inpatient induction the next day. Some do multiple daily doses over the course of a week.

Conclusion

While the data continue to be limited, we strongly believe there is sufficient quality evidence from a safety and efficacy perspective to support implementation and evaluation of outpatient cervical ripening protocols for low-risk pregnancies. In the setting of renewed commitments to reducing suboptimal health care costs and utilization as well as increasing patient satisfaction and control in their birthing experiences, we posit it is the responsibility of obstetricians, L&D leadership, and health care institutions to explore the implementation of outpatient cervical ripening for appropriate candidates in their settings.

The Diagnosis: Nipple Adenoma (Florid Papillomatosis of the Nipple) 

Biopsy of the nodule showed florid papillary hyperplasia of the ductal epithelium within the dermis that was sharply demarcated from the background stroma (Figure, A and B). Neither cytological nor architectural atypia were evident. There was no notable necrosis (Figure C). There was a background of fibrosis whereby the glandular ductal structures assumed a somewhat irregular growth pattern within the dermis with attendant hemorrhage. The patient underwent complete excision of the lesion. No evidence of carcinoma was seen on the final pathology, and the final margins were negative. 

First described in 1923 and fully characterized in 1955, nipple adenoma (also known as florid papillomatosis of the nipple) is a benign proliferative neoplasm that originates in the lactiferous ducts of the nipple.^1,2 It most commonly affects women aged 40 to 50 years (range, 0-89 years); less than 5% of cases are reported in men.^3,4 It predominantly is unilateral, with only rare cases of bilateral papillomatosis reported. Patients often present with serous or serosanguineous discharge and an itching or burning sensation. Symptoms may worsen with the menstrual cycle.⁴ On physical examination, it presents as an ill-defined red nodule on the nipple with crusting, erosion, or erythema of the nipple surface. Although imaging generally is not used to confirm the diagnosis, mammography should be performed prior to biopsy to rule out underlying breast pathology. Dermoscopy may show linear cherry red structures or red serpiginous and annular structures.^5,6 The differential diagnosis of nipple adenoma includes Paget disease of the breast, adenomyoepithelioma, subareolar subsclerosing duct hyperplasia, syringomatous adenoma, adenosis tumor, low-grade adenosquamous carcinoma, low-grade ductal carcinoma in situ, tubular carcinoma, and sweat gland tumors.³  

Microscopic features of nipple adenoma have been categorized into 4 subtypes: sclerosing papillomatosis, papillomatosis, adenosis, and a mixed pattern.^3,7 The tumors may have keratin cysts and focal necrosis but no atypia, and the myoepithelial cell layer is retained. Nipple adenomas show a glandular proliferation in the dermis that is relatively well circumscribed with glands that vary in appearance between a simple adenosislike pattern of growth to a papillary hyperplasia and/or usual ductal hyperplasia growth pattern. A pseudoinfiltrative pattern can occur when the glandular epithelium is entrapped within stromal fibrosis; however, the myoepithelial layer is retained. Occasionally, the glandular epithelium can grow in continuity with the surface squamous epithelium of the nipple, clinically simulating Paget disease of the breast.⁸ Immunohistochemical stains, specifically p63, p40, calponin 1, h-caldesmon, cytokeratin 5/6, CD10, and α; smooth muscle actin, highlight the myoepithelial cells, while cytokeratin 7 identifies the ductal epithelium, supporting the diagnosis.⁶ In addition to biopsy and microscopic tissue examination, touch preparation cytology, curettage cytology, and fine needle aspiration techniques have been used to perform cytologic examination of the lesions, aiding in identification of the benign or malignant nature of the neoplasm.⁶ Nipple adenoma also is referred to as florid papillomatosis of the nipple, papillary adenoma, erosive adenomatosis, and subareolar duct papillomatosis.⁷ 

Although nipple adenoma is a benign tumor, up to 16.5% of affected patients had an ipsilateral or contralateral mammary carcinoma.⁹ The majority arose coincidentally but separately in the same breast, and carcinoma arose directly from the nipple adenoma in 8 cases; 3 cases were carcinomas that arose in men.¹⁰ A definitive association or causal relationship between nipple adenoma and subsequent development of breast cancer has not been identified, and the incidence of nipple adenoma in patients with a positive family history of breast cancer has not been examined. Therefore, although various treatments including cryosurgery, nipple splitting enucleation, and Mohs micrographic surgery have been proposed, complete excision remains the gold standard of therapy. Regular breast examinations and digital mammography are necessary to screen for local recurrences.  

The Diagnosis: Nipple Adenoma (Florid Papillomatosis of the Nipple) 

Biopsy of the nodule showed florid papillary hyperplasia of the ductal epithelium within the dermis that was sharply demarcated from the background stroma (Figure, A and B). Neither cytological nor architectural atypia were evident. There was no notable necrosis (Figure C). There was a background of fibrosis whereby the glandular ductal structures assumed a somewhat irregular growth pattern within the dermis with attendant hemorrhage. The patient underwent complete excision of the lesion. No evidence of carcinoma was seen on the final pathology, and the final margins were negative. 

First described in 1923 and fully characterized in 1955, nipple adenoma (also known as florid papillomatosis of the nipple) is a benign proliferative neoplasm that originates in the lactiferous ducts of the nipple.^1,2 It most commonly affects women aged 40 to 50 years (range, 0-89 years); less than 5% of cases are reported in men.^3,4 It predominantly is unilateral, with only rare cases of bilateral papillomatosis reported. Patients often present with serous or serosanguineous discharge and an itching or burning sensation. Symptoms may worsen with the menstrual cycle.⁴ On physical examination, it presents as an ill-defined red nodule on the nipple with crusting, erosion, or erythema of the nipple surface. Although imaging generally is not used to confirm the diagnosis, mammography should be performed prior to biopsy to rule out underlying breast pathology. Dermoscopy may show linear cherry red structures or red serpiginous and annular structures.^5,6 The differential diagnosis of nipple adenoma includes Paget disease of the breast, adenomyoepithelioma, subareolar subsclerosing duct hyperplasia, syringomatous adenoma, adenosis tumor, low-grade adenosquamous carcinoma, low-grade ductal carcinoma in situ, tubular carcinoma, and sweat gland tumors.³  

Microscopic features of nipple adenoma have been categorized into 4 subtypes: sclerosing papillomatosis, papillomatosis, adenosis, and a mixed pattern.^3,7 The tumors may have keratin cysts and focal necrosis but no atypia, and the myoepithelial cell layer is retained. Nipple adenomas show a glandular proliferation in the dermis that is relatively well circumscribed with glands that vary in appearance between a simple adenosislike pattern of growth to a papillary hyperplasia and/or usual ductal hyperplasia growth pattern. A pseudoinfiltrative pattern can occur when the glandular epithelium is entrapped within stromal fibrosis; however, the myoepithelial layer is retained. Occasionally, the glandular epithelium can grow in continuity with the surface squamous epithelium of the nipple, clinically simulating Paget disease of the breast.⁸ Immunohistochemical stains, specifically p63, p40, calponin 1, h-caldesmon, cytokeratin 5/6, CD10, and α; smooth muscle actin, highlight the myoepithelial cells, while cytokeratin 7 identifies the ductal epithelium, supporting the diagnosis.⁶ In addition to biopsy and microscopic tissue examination, touch preparation cytology, curettage cytology, and fine needle aspiration techniques have been used to perform cytologic examination of the lesions, aiding in identification of the benign or malignant nature of the neoplasm.⁶ Nipple adenoma also is referred to as florid papillomatosis of the nipple, papillary adenoma, erosive adenomatosis, and subareolar duct papillomatosis.⁷ 

Although nipple adenoma is a benign tumor, up to 16.5% of affected patients had an ipsilateral or contralateral mammary carcinoma.⁹ The majority arose coincidentally but separately in the same breast, and carcinoma arose directly from the nipple adenoma in 8 cases; 3 cases were carcinomas that arose in men.¹⁰ A definitive association or causal relationship between nipple adenoma and subsequent development of breast cancer has not been identified, and the incidence of nipple adenoma in patients with a positive family history of breast cancer has not been examined. Therefore, although various treatments including cryosurgery, nipple splitting enucleation, and Mohs micrographic surgery have been proposed, complete excision remains the gold standard of therapy. Regular breast examinations and digital mammography are necessary to screen for local recurrences.  

The Diagnosis: Nipple Adenoma (Florid Papillomatosis of the Nipple) 

Biopsy of the nodule showed florid papillary hyperplasia of the ductal epithelium within the dermis that was sharply demarcated from the background stroma (Figure, A and B). Neither cytological nor architectural atypia were evident. There was no notable necrosis (Figure C). There was a background of fibrosis whereby the glandular ductal structures assumed a somewhat irregular growth pattern within the dermis with attendant hemorrhage. The patient underwent complete excision of the lesion. No evidence of carcinoma was seen on the final pathology, and the final margins were negative. 

First described in 1923 and fully characterized in 1955, nipple adenoma (also known as florid papillomatosis of the nipple) is a benign proliferative neoplasm that originates in the lactiferous ducts of the nipple.^1,2 It most commonly affects women aged 40 to 50 years (range, 0-89 years); less than 5% of cases are reported in men.^3,4 It predominantly is unilateral, with only rare cases of bilateral papillomatosis reported. Patients often present with serous or serosanguineous discharge and an itching or burning sensation. Symptoms may worsen with the menstrual cycle.⁴ On physical examination, it presents as an ill-defined red nodule on the nipple with crusting, erosion, or erythema of the nipple surface. Although imaging generally is not used to confirm the diagnosis, mammography should be performed prior to biopsy to rule out underlying breast pathology. Dermoscopy may show linear cherry red structures or red serpiginous and annular structures.^5,6 The differential diagnosis of nipple adenoma includes Paget disease of the breast, adenomyoepithelioma, subareolar subsclerosing duct hyperplasia, syringomatous adenoma, adenosis tumor, low-grade adenosquamous carcinoma, low-grade ductal carcinoma in situ, tubular carcinoma, and sweat gland tumors.³  

Microscopic features of nipple adenoma have been categorized into 4 subtypes: sclerosing papillomatosis, papillomatosis, adenosis, and a mixed pattern.^3,7 The tumors may have keratin cysts and focal necrosis but no atypia, and the myoepithelial cell layer is retained. Nipple adenomas show a glandular proliferation in the dermis that is relatively well circumscribed with glands that vary in appearance between a simple adenosislike pattern of growth to a papillary hyperplasia and/or usual ductal hyperplasia growth pattern. A pseudoinfiltrative pattern can occur when the glandular epithelium is entrapped within stromal fibrosis; however, the myoepithelial layer is retained. Occasionally, the glandular epithelium can grow in continuity with the surface squamous epithelium of the nipple, clinically simulating Paget disease of the breast.⁸ Immunohistochemical stains, specifically p63, p40, calponin 1, h-caldesmon, cytokeratin 5/6, CD10, and α; smooth muscle actin, highlight the myoepithelial cells, while cytokeratin 7 identifies the ductal epithelium, supporting the diagnosis.⁶ In addition to biopsy and microscopic tissue examination, touch preparation cytology, curettage cytology, and fine needle aspiration techniques have been used to perform cytologic examination of the lesions, aiding in identification of the benign or malignant nature of the neoplasm.⁶ Nipple adenoma also is referred to as florid papillomatosis of the nipple, papillary adenoma, erosive adenomatosis, and subareolar duct papillomatosis.⁷ 

Although nipple adenoma is a benign tumor, up to 16.5% of affected patients had an ipsilateral or contralateral mammary carcinoma.⁹ The majority arose coincidentally but separately in the same breast, and carcinoma arose directly from the nipple adenoma in 8 cases; 3 cases were carcinomas that arose in men.¹⁰ A definitive association or causal relationship between nipple adenoma and subsequent development of breast cancer has not been identified, and the incidence of nipple adenoma in patients with a positive family history of breast cancer has not been examined. Therefore, although various treatments including cryosurgery, nipple splitting enucleation, and Mohs micrographic surgery have been proposed, complete excision remains the gold standard of therapy. Regular breast examinations and digital mammography are necessary to screen for local recurrences.  

Choose your answer in the poll below. To check the accuracy of your answer, see Endocrine Consult: 10 (Safe) Ways to Reduce Patients’ Insulin Costs.

[polldaddy:10400221]

Click on page 2 below to find out what the correct answer is...

The correct answer is d.) 500%

To learn more, see this month's Endocrine Consult: 10 (Safe) Ways to Reduce Patients’ Insulin Costs.

Choose your answer in the poll below. To check the accuracy of your answer, see Endocrine Consult: 10 (Safe) Ways to Reduce Patients’ Insulin Costs.

[polldaddy:10400221]

Click on page 2 below to find out what the correct answer is...

The correct answer is d.) 500%

To learn more, see this month's Endocrine Consult: 10 (Safe) Ways to Reduce Patients’ Insulin Costs.

Choose your answer in the poll below. To check the accuracy of your answer, see Endocrine Consult: 10 (Safe) Ways to Reduce Patients’ Insulin Costs.

[polldaddy:10400221]

Click on page 2 below to find out what the correct answer is...

The correct answer is d.) 500%

To learn more, see this month's Endocrine Consult: 10 (Safe) Ways to Reduce Patients’ Insulin Costs.

Medication to help prevent breast cancer is not recommended for women without increased risk, but could benefit women at increased risk for the disease, according to an update from the U.S. Preventive Services Task Force.

Dr. Cecil Fox/National Cancer Institute

SOURCEs: Owens DK et al. JAMA. 2019 Sept 3. doi: 10.1001/jama.2019.11885; Nelson HD et al. JAMA. 2019 Sept 3. doi: 10.1001/jama.2019.5780.

Medication to help prevent breast cancer is not recommended for women without increased risk, but could benefit women at increased risk for the disease, according to an update from the U.S. Preventive Services Task Force.

Dr. Cecil Fox/National Cancer Institute

SOURCEs: Owens DK et al. JAMA. 2019 Sept 3. doi: 10.1001/jama.2019.11885; Nelson HD et al. JAMA. 2019 Sept 3. doi: 10.1001/jama.2019.5780.

Medication to help prevent breast cancer is not recommended for women without increased risk, but could benefit women at increased risk for the disease, according to an update from the U.S. Preventive Services Task Force.

Dr. Cecil Fox/National Cancer Institute

SOURCEs: Owens DK et al. JAMA. 2019 Sept 3. doi: 10.1001/jama.2019.11885; Nelson HD et al. JAMA. 2019 Sept 3. doi: 10.1001/jama.2019.5780.

Almost a century after its discovery, insulin remains a life-saving yet costly medication: In the past 15 years, prices have risen more than 500%.¹ Patients may ask you why the insulin you prescribe is so expensive, and the complex process for determining drug costs makes it difficult to answer. But the bottom line is, patients need their insulin—and they want it without breaking the bank.

Thankfully, there are several strategies for reducing the cost of insulin. First and foremost, patients must be advised that not taking their prescribed insulin, or taking less insulin than prescribed, is not a safe alternative. An individualized cost-benefit analysis between patient and provider can help to determine the best option for each patient. After working in endocrinology for 5 years, I have learned the following 10 ways to help patients whose financial situations limit their access to insulin.

1 Try older insulins, including mixed insulin 70/30 or 50/50, insulin NPH, or regular insulin. Because the beneficial effects may not be as long lasting with these as with newer insulins on the market, your patient may need to test glucose levels more frequently. Also, insulin NPH and any mixed insulins are suspensions, not solutions, so patients will need to gently roll older insulins prior to use. Those in pen form may also have a shorter shelf life.

2 Switch to a syringe and vial. Although dosing can be less precise, this could be a viable option for patients with good vision and dexterity. This method helps patients save in 3 ways: (1) the insulin is less expensive; (2) syringes generally cost less (about $30 for 100) than pen needle tips (about $50 for 100); and (3) vials of NPH are longer-lasting suspensions that are stable for about 28 days once opened, compared to 14 days for pens.^2-4

3 Switch from a 30- to a 90-day supply of refills. This helps to lower copays. For example, a mail-order program (eg, Express Scripts) that ships from a warehouse typically offers lower pricing than a brick-and-mortar pharmacy with greater overhead. Many of these programs provide 2-pharmacist verification for accuracy and free home delivery of medications at a 10% discount, as well as 24-hour pharmacist access.⁵ The ease of obtaining prescriptions by this method also can help with medication adherence.

4 Patient assistance programs (PAPs) offered by insulin manufacturers can help lower costs for patients who find it difficult to afford their medication. Information on these programs is available on the respective company’s websites, usually in multiple languages (although some are limited to English and Spanish). Patients applying for a PAP must provide a proof of income and adhere to the program’s specific criteria. Renewal is typically required each year.^6-8

5 Copay cards are available to many patients with private insurance and may help make insulin more affordable. Patients may be able to receive a $25 monthly supply of insulin for up to 1 year (specific terms vary). Maximum contributions and contributions toward deductibles also vary by program, so patients need to familiarize themselves with what their particular copay card allows. Generally, copay cards are not a sustainable long-term solution; for one thing, they expire, and for another, emphasis should be placed on affordable medications rather than affording expensive medications.

[polldaddy:10400221]

Continue to: 6 External PAPs for patients on Medicare...

6 External PAPs for patients on Medicare can help lower the costs of prescription medications.⁹ A database of pharmaceutical PAPs is available on the Medicare website.¹⁰ Some PAPs may help patients on Medicare pay through the $5,100 coverage gap or “donut hole”—a term referring to a gap in prescription drug coverage once patients have met their prescription limit (all Medicare part D plans have a donut hole).^11,12 Patients and providers will need to read the fine print when applying for an external PAP, because some have a monthly or one-time start-up fee for processing the paperwork (and note, there is often paperwork for the relief program in addition to the PAP paperwork through the pharmaceutical company).

7 A Program of All-Inclusive Care for the Elderly (PACE) is available in many states; check medicare.gov to see if your state is eligible. For patients 55 and older on Medicare or Medicaid who do not opt for care at a nursing home facility, PACE may be able to provide care and coverage in the patient’s home or at a PACE facility. Services include primary care, hospital care, laboratory and x-ray services, medical specialty services, and prescription drugs. To be eligible for PACE services, the patient must live in the service area of a PACE organization and have a requirement for a nursing home-level of care (as certified by your state).

8 Shop around for the best deal. Encourage your patients to comparison shop for the best prices rather than accepting the first or only option at their usual pharmacy. Different pharmacies offer drugs at lower prices than competitors. Also, continually compare prices at GoodRx or HealthWarehouse.com. The latter—a fully licensed Internet-based pharmacy—sells FDA-approved medications at affordable prices in all 50 states, without the requirement for insurance coverage.

9 Use of a patch pump may be less expensive for patients with type 2 diabetes who are taking basal-bolus regimens. Patches slowly deliver single short-acting insulin (usually insulin aspart or lispro) that acts as a basal insulin, with an additional reservoir for prandial insulin at mealtime and for snacks. As there is a catheter in the patch, patients would not require the use of needles.¹³

10 Try removing mealtime insulin for patients with type 2 diabetes who need minimal mealtime insulin. Clinicians can initiate a safe trial of this removal by encouraging the patient to consume a low-carbohydrate diet, increase exercise, and/or use other noninsulin medications that are more affordable.

Continue to: The affordability of insulins...

The affordability of insulins is a potentially uncomfortable but necessary conversation to have with your patient. Providers are one of the best resources for patients who seek relief from financial difficulties. The recommendations discussed here can help providers and patients design a cost-conscious plan for insulin treatment. Although each recommendation is viable, the pros and cons must be weighed on a case-by-case basis. Providers and patients should also pay attention to the Senate Finance Committee’s ongoing discussions and possible resolutions that could result in lower insulin costs. Until legislation that lowers the prices of insulin comes to fruition, however, providers should continue to plan with their patients on how to best get their insulin at the lowest cost.

Test yourself with the poll here.

Almost a century after its discovery, insulin remains a life-saving yet costly medication: In the past 15 years, prices have risen more than 500%.¹ Patients may ask you why the insulin you prescribe is so expensive, and the complex process for determining drug costs makes it difficult to answer. But the bottom line is, patients need their insulin—and they want it without breaking the bank.

Thankfully, there are several strategies for reducing the cost of insulin. First and foremost, patients must be advised that not taking their prescribed insulin, or taking less insulin than prescribed, is not a safe alternative. An individualized cost-benefit analysis between patient and provider can help to determine the best option for each patient. After working in endocrinology for 5 years, I have learned the following 10 ways to help patients whose financial situations limit their access to insulin.

1 Try older insulins, including mixed insulin 70/30 or 50/50, insulin NPH, or regular insulin. Because the beneficial effects may not be as long lasting with these as with newer insulins on the market, your patient may need to test glucose levels more frequently. Also, insulin NPH and any mixed insulins are suspensions, not solutions, so patients will need to gently roll older insulins prior to use. Those in pen form may also have a shorter shelf life.

2 Switch to a syringe and vial. Although dosing can be less precise, this could be a viable option for patients with good vision and dexterity. This method helps patients save in 3 ways: (1) the insulin is less expensive; (2) syringes generally cost less (about $30 for 100) than pen needle tips (about $50 for 100); and (3) vials of NPH are longer-lasting suspensions that are stable for about 28 days once opened, compared to 14 days for pens.^2-4

3 Switch from a 30- to a 90-day supply of refills. This helps to lower copays. For example, a mail-order program (eg, Express Scripts) that ships from a warehouse typically offers lower pricing than a brick-and-mortar pharmacy with greater overhead. Many of these programs provide 2-pharmacist verification for accuracy and free home delivery of medications at a 10% discount, as well as 24-hour pharmacist access.⁵ The ease of obtaining prescriptions by this method also can help with medication adherence.

4 Patient assistance programs (PAPs) offered by insulin manufacturers can help lower costs for patients who find it difficult to afford their medication. Information on these programs is available on the respective company’s websites, usually in multiple languages (although some are limited to English and Spanish). Patients applying for a PAP must provide a proof of income and adhere to the program’s specific criteria. Renewal is typically required each year.^6-8

5 Copay cards are available to many patients with private insurance and may help make insulin more affordable. Patients may be able to receive a $25 monthly supply of insulin for up to 1 year (specific terms vary). Maximum contributions and contributions toward deductibles also vary by program, so patients need to familiarize themselves with what their particular copay card allows. Generally, copay cards are not a sustainable long-term solution; for one thing, they expire, and for another, emphasis should be placed on affordable medications rather than affording expensive medications.

[polldaddy:10400221]

Continue to: 6 External PAPs for patients on Medicare...

6 External PAPs for patients on Medicare can help lower the costs of prescription medications.⁹ A database of pharmaceutical PAPs is available on the Medicare website.¹⁰ Some PAPs may help patients on Medicare pay through the $5,100 coverage gap or “donut hole”—a term referring to a gap in prescription drug coverage once patients have met their prescription limit (all Medicare part D plans have a donut hole).^11,12 Patients and providers will need to read the fine print when applying for an external PAP, because some have a monthly or one-time start-up fee for processing the paperwork (and note, there is often paperwork for the relief program in addition to the PAP paperwork through the pharmaceutical company).

7 A Program of All-Inclusive Care for the Elderly (PACE) is available in many states; check medicare.gov to see if your state is eligible. For patients 55 and older on Medicare or Medicaid who do not opt for care at a nursing home facility, PACE may be able to provide care and coverage in the patient’s home or at a PACE facility. Services include primary care, hospital care, laboratory and x-ray services, medical specialty services, and prescription drugs. To be eligible for PACE services, the patient must live in the service area of a PACE organization and have a requirement for a nursing home-level of care (as certified by your state).

8 Shop around for the best deal. Encourage your patients to comparison shop for the best prices rather than accepting the first or only option at their usual pharmacy. Different pharmacies offer drugs at lower prices than competitors. Also, continually compare prices at GoodRx or HealthWarehouse.com. The latter—a fully licensed Internet-based pharmacy—sells FDA-approved medications at affordable prices in all 50 states, without the requirement for insurance coverage.

9 Use of a patch pump may be less expensive for patients with type 2 diabetes who are taking basal-bolus regimens. Patches slowly deliver single short-acting insulin (usually insulin aspart or lispro) that acts as a basal insulin, with an additional reservoir for prandial insulin at mealtime and for snacks. As there is a catheter in the patch, patients would not require the use of needles.¹³

10 Try removing mealtime insulin for patients with type 2 diabetes who need minimal mealtime insulin. Clinicians can initiate a safe trial of this removal by encouraging the patient to consume a low-carbohydrate diet, increase exercise, and/or use other noninsulin medications that are more affordable.

Continue to: The affordability of insulins...

The affordability of insulins is a potentially uncomfortable but necessary conversation to have with your patient. Providers are one of the best resources for patients who seek relief from financial difficulties. The recommendations discussed here can help providers and patients design a cost-conscious plan for insulin treatment. Although each recommendation is viable, the pros and cons must be weighed on a case-by-case basis. Providers and patients should also pay attention to the Senate Finance Committee’s ongoing discussions and possible resolutions that could result in lower insulin costs. Until legislation that lowers the prices of insulin comes to fruition, however, providers should continue to plan with their patients on how to best get their insulin at the lowest cost.

Test yourself with the poll here.

Almost a century after its discovery, insulin remains a life-saving yet costly medication: In the past 15 years, prices have risen more than 500%.¹ Patients may ask you why the insulin you prescribe is so expensive, and the complex process for determining drug costs makes it difficult to answer. But the bottom line is, patients need their insulin—and they want it without breaking the bank.

Thankfully, there are several strategies for reducing the cost of insulin. First and foremost, patients must be advised that not taking their prescribed insulin, or taking less insulin than prescribed, is not a safe alternative. An individualized cost-benefit analysis between patient and provider can help to determine the best option for each patient. After working in endocrinology for 5 years, I have learned the following 10 ways to help patients whose financial situations limit their access to insulin.

1 Try older insulins, including mixed insulin 70/30 or 50/50, insulin NPH, or regular insulin. Because the beneficial effects may not be as long lasting with these as with newer insulins on the market, your patient may need to test glucose levels more frequently. Also, insulin NPH and any mixed insulins are suspensions, not solutions, so patients will need to gently roll older insulins prior to use. Those in pen form may also have a shorter shelf life.

2 Switch to a syringe and vial. Although dosing can be less precise, this could be a viable option for patients with good vision and dexterity. This method helps patients save in 3 ways: (1) the insulin is less expensive; (2) syringes generally cost less (about $30 for 100) than pen needle tips (about $50 for 100); and (3) vials of NPH are longer-lasting suspensions that are stable for about 28 days once opened, compared to 14 days for pens.^2-4

3 Switch from a 30- to a 90-day supply of refills. This helps to lower copays. For example, a mail-order program (eg, Express Scripts) that ships from a warehouse typically offers lower pricing than a brick-and-mortar pharmacy with greater overhead. Many of these programs provide 2-pharmacist verification for accuracy and free home delivery of medications at a 10% discount, as well as 24-hour pharmacist access.⁵ The ease of obtaining prescriptions by this method also can help with medication adherence.

4 Patient assistance programs (PAPs) offered by insulin manufacturers can help lower costs for patients who find it difficult to afford their medication. Information on these programs is available on the respective company’s websites, usually in multiple languages (although some are limited to English and Spanish). Patients applying for a PAP must provide a proof of income and adhere to the program’s specific criteria. Renewal is typically required each year.^6-8

5 Copay cards are available to many patients with private insurance and may help make insulin more affordable. Patients may be able to receive a $25 monthly supply of insulin for up to 1 year (specific terms vary). Maximum contributions and contributions toward deductibles also vary by program, so patients need to familiarize themselves with what their particular copay card allows. Generally, copay cards are not a sustainable long-term solution; for one thing, they expire, and for another, emphasis should be placed on affordable medications rather than affording expensive medications.

[polldaddy:10400221]

Continue to: 6 External PAPs for patients on Medicare...

6 External PAPs for patients on Medicare can help lower the costs of prescription medications.⁹ A database of pharmaceutical PAPs is available on the Medicare website.¹⁰ Some PAPs may help patients on Medicare pay through the $5,100 coverage gap or “donut hole”—a term referring to a gap in prescription drug coverage once patients have met their prescription limit (all Medicare part D plans have a donut hole).^11,12 Patients and providers will need to read the fine print when applying for an external PAP, because some have a monthly or one-time start-up fee for processing the paperwork (and note, there is often paperwork for the relief program in addition to the PAP paperwork through the pharmaceutical company).

7 A Program of All-Inclusive Care for the Elderly (PACE) is available in many states; check medicare.gov to see if your state is eligible. For patients 55 and older on Medicare or Medicaid who do not opt for care at a nursing home facility, PACE may be able to provide care and coverage in the patient’s home or at a PACE facility. Services include primary care, hospital care, laboratory and x-ray services, medical specialty services, and prescription drugs. To be eligible for PACE services, the patient must live in the service area of a PACE organization and have a requirement for a nursing home-level of care (as certified by your state).

8 Shop around for the best deal. Encourage your patients to comparison shop for the best prices rather than accepting the first or only option at their usual pharmacy. Different pharmacies offer drugs at lower prices than competitors. Also, continually compare prices at GoodRx or HealthWarehouse.com. The latter—a fully licensed Internet-based pharmacy—sells FDA-approved medications at affordable prices in all 50 states, without the requirement for insurance coverage.

9 Use of a patch pump may be less expensive for patients with type 2 diabetes who are taking basal-bolus regimens. Patches slowly deliver single short-acting insulin (usually insulin aspart or lispro) that acts as a basal insulin, with an additional reservoir for prandial insulin at mealtime and for snacks. As there is a catheter in the patch, patients would not require the use of needles.¹³

10 Try removing mealtime insulin for patients with type 2 diabetes who need minimal mealtime insulin. Clinicians can initiate a safe trial of this removal by encouraging the patient to consume a low-carbohydrate diet, increase exercise, and/or use other noninsulin medications that are more affordable.

Continue to: The affordability of insulins...

The affordability of insulins is a potentially uncomfortable but necessary conversation to have with your patient. Providers are one of the best resources for patients who seek relief from financial difficulties. The recommendations discussed here can help providers and patients design a cost-conscious plan for insulin treatment. Although each recommendation is viable, the pros and cons must be weighed on a case-by-case basis. Providers and patients should also pay attention to the Senate Finance Committee’s ongoing discussions and possible resolutions that could result in lower insulin costs. Until legislation that lowers the prices of insulin comes to fruition, however, providers should continue to plan with their patients on how to best get their insulin at the lowest cost.

Test yourself with the poll here.

Genotype-guided selection of oral P2Y ₁₂ inhibitors for patients having percutaneous coronary intervention with stent implantation derives no clinical benefits overall when compared to standard treatment, according to results of the large, randomized POPular Genetics trial, although genotype guidance did result in lower rates of primary minor bleeding.

The study was presented at the annual congress of the European Society of Cardiology Study in Paris and published simultaneously in the New England Journal of Medicine.

CDC/Janice Carr

POPular Genetics (CYP2C19 Genotype-Guided Antiplatelet Therapy in ST-Segment Elevation Myocardial Infarction Patients – Patient Outcome After Primary PCI) randomized 2,488 patients who had PCI to either P2Y₁₂ inhibitor on the basis of early genetic testing for the CYP2C19 gene (1,242 patients) or standard treatment with either ticagrelor or prasugrel (1,246 patients) for 12 months. In the genotype-guided group, patients were assigned to one of two arms depending on results; carriers of CYP2C19*2 or CYP2C19*3 loss-of-function alleles received ticagrelor or prasugrel, and non-carriers receive clopidogrel. The study was conducted from Jun. 2011 to Apr. 2018.

Net adverse clinical events, which included any-cause death, myocardial infarction, stent thrombosis, stroke or major bleeding based on the Platelet Inhibition and Patient Outcomes (PLATO) criteria at 12 months were similar between both groups: 5.1% in the genotype-guided patients and 5.9% in the standard-treatment group (P less than .001), but rates of PLATO major or minor bleeding were 9.8% and 12.5%, respectively (P = .04).

When secondary outcomes were evaluated, no significant differences emerged between the two groups. Secondary outcomes included combined thrombotic outcomes (death from vascular causes, myocardial infarction, stent thrombosis or stroke; 2.7% for the genotype-guided group vs. 3.3% in the standard-treatment group), and PLATO major bleeding (2.3% in both groups). The difference in the primary bleeding outcomes between the groups was driven by a lower incidence of PLATO minor bleeding in the genotype-guided group, 7.6% vs. 10.5%.

The two takeaways from POPular Genetics, said Daniel M.F. Claassens, MD, and coauthors, are that giving clopidogrel to patients without a CYP2C19 loss-of-function allele did not elevate their risk of combined any-cause death and other adverse cardiac outcomes, including major bleeding, 12 months after PCI; and that giving clopidogrel to the genotype-guided group lowered the risk of minor bleeding.

Dr. Claassens and coauthors noted that since the Netherlands trial was designed in 2011, the development of newer-generation stents has considerably lowered rates of thrombotic events after acute coronary syndromes. “With the lower-than-anticipated incidence of the primary combined outcome in our trial, the prespecified noninferiority margin was wider relative to the incidence than originally expected,” they said. While the primary combined outcome was 21% higher than the incidence in the standard-treatment group at the upper end of the 95% confidence interval, the incidence was 11% higher in the standard-treatment group at the observed upper end of the 95% CI. This “gives stronger support to the conclusion that genotype-guided P2Y₁₂ treatment is noninferior to standard treatment for the occurrence of thrombotic events,” Dr. Claassens and coauthors said.

The study report noted a number of limitations, including that more polymorphisms of the CyP2C19 gene may be linked to increased thrombotic or bleeding risk. “Therefore, our strategy based solely on the CYP2C19 genotype may not be the most useful strategy for some patients,” Dr. Claassens and coauthors said.

POPular Genetics received funding from the Netherlands Organization for Health Research and Development (ZonMw). Dr. Claassens receives grants from ZonMw and non-financial support from Spartan Biosciences.

SOURCE: Claassens DMF, et al. N Engl J. Med. Published online September 3, doi.org/10.1016/S0140-6736(19)31996-8.

Genotype-guided selection of oral P2Y ₁₂ inhibitors for patients having percutaneous coronary intervention with stent implantation derives no clinical benefits overall when compared to standard treatment, according to results of the large, randomized POPular Genetics trial, although genotype guidance did result in lower rates of primary minor bleeding.

The study was presented at the annual congress of the European Society of Cardiology Study in Paris and published simultaneously in the New England Journal of Medicine.

CDC/Janice Carr

POPular Genetics (CYP2C19 Genotype-Guided Antiplatelet Therapy in ST-Segment Elevation Myocardial Infarction Patients – Patient Outcome After Primary PCI) randomized 2,488 patients who had PCI to either P2Y₁₂ inhibitor on the basis of early genetic testing for the CYP2C19 gene (1,242 patients) or standard treatment with either ticagrelor or prasugrel (1,246 patients) for 12 months. In the genotype-guided group, patients were assigned to one of two arms depending on results; carriers of CYP2C19*2 or CYP2C19*3 loss-of-function alleles received ticagrelor or prasugrel, and non-carriers receive clopidogrel. The study was conducted from Jun. 2011 to Apr. 2018.

Net adverse clinical events, which included any-cause death, myocardial infarction, stent thrombosis, stroke or major bleeding based on the Platelet Inhibition and Patient Outcomes (PLATO) criteria at 12 months were similar between both groups: 5.1% in the genotype-guided patients and 5.9% in the standard-treatment group (P less than .001), but rates of PLATO major or minor bleeding were 9.8% and 12.5%, respectively (P = .04).

When secondary outcomes were evaluated, no significant differences emerged between the two groups. Secondary outcomes included combined thrombotic outcomes (death from vascular causes, myocardial infarction, stent thrombosis or stroke; 2.7% for the genotype-guided group vs. 3.3% in the standard-treatment group), and PLATO major bleeding (2.3% in both groups). The difference in the primary bleeding outcomes between the groups was driven by a lower incidence of PLATO minor bleeding in the genotype-guided group, 7.6% vs. 10.5%.

The two takeaways from POPular Genetics, said Daniel M.F. Claassens, MD, and coauthors, are that giving clopidogrel to patients without a CYP2C19 loss-of-function allele did not elevate their risk of combined any-cause death and other adverse cardiac outcomes, including major bleeding, 12 months after PCI; and that giving clopidogrel to the genotype-guided group lowered the risk of minor bleeding.

Dr. Claassens and coauthors noted that since the Netherlands trial was designed in 2011, the development of newer-generation stents has considerably lowered rates of thrombotic events after acute coronary syndromes. “With the lower-than-anticipated incidence of the primary combined outcome in our trial, the prespecified noninferiority margin was wider relative to the incidence than originally expected,” they said. While the primary combined outcome was 21% higher than the incidence in the standard-treatment group at the upper end of the 95% confidence interval, the incidence was 11% higher in the standard-treatment group at the observed upper end of the 95% CI. This “gives stronger support to the conclusion that genotype-guided P2Y₁₂ treatment is noninferior to standard treatment for the occurrence of thrombotic events,” Dr. Claassens and coauthors said.

The study report noted a number of limitations, including that more polymorphisms of the CyP2C19 gene may be linked to increased thrombotic or bleeding risk. “Therefore, our strategy based solely on the CYP2C19 genotype may not be the most useful strategy for some patients,” Dr. Claassens and coauthors said.

POPular Genetics received funding from the Netherlands Organization for Health Research and Development (ZonMw). Dr. Claassens receives grants from ZonMw and non-financial support from Spartan Biosciences.

SOURCE: Claassens DMF, et al. N Engl J. Med. Published online September 3, doi.org/10.1016/S0140-6736(19)31996-8.

Genotype-guided selection of oral P2Y ₁₂ inhibitors for patients having percutaneous coronary intervention with stent implantation derives no clinical benefits overall when compared to standard treatment, according to results of the large, randomized POPular Genetics trial, although genotype guidance did result in lower rates of primary minor bleeding.

The study was presented at the annual congress of the European Society of Cardiology Study in Paris and published simultaneously in the New England Journal of Medicine.

CDC/Janice Carr

POPular Genetics (CYP2C19 Genotype-Guided Antiplatelet Therapy in ST-Segment Elevation Myocardial Infarction Patients – Patient Outcome After Primary PCI) randomized 2,488 patients who had PCI to either P2Y₁₂ inhibitor on the basis of early genetic testing for the CYP2C19 gene (1,242 patients) or standard treatment with either ticagrelor or prasugrel (1,246 patients) for 12 months. In the genotype-guided group, patients were assigned to one of two arms depending on results; carriers of CYP2C19*2 or CYP2C19*3 loss-of-function alleles received ticagrelor or prasugrel, and non-carriers receive clopidogrel. The study was conducted from Jun. 2011 to Apr. 2018.

Net adverse clinical events, which included any-cause death, myocardial infarction, stent thrombosis, stroke or major bleeding based on the Platelet Inhibition and Patient Outcomes (PLATO) criteria at 12 months were similar between both groups: 5.1% in the genotype-guided patients and 5.9% in the standard-treatment group (P less than .001), but rates of PLATO major or minor bleeding were 9.8% and 12.5%, respectively (P = .04).

When secondary outcomes were evaluated, no significant differences emerged between the two groups. Secondary outcomes included combined thrombotic outcomes (death from vascular causes, myocardial infarction, stent thrombosis or stroke; 2.7% for the genotype-guided group vs. 3.3% in the standard-treatment group), and PLATO major bleeding (2.3% in both groups). The difference in the primary bleeding outcomes between the groups was driven by a lower incidence of PLATO minor bleeding in the genotype-guided group, 7.6% vs. 10.5%.

The two takeaways from POPular Genetics, said Daniel M.F. Claassens, MD, and coauthors, are that giving clopidogrel to patients without a CYP2C19 loss-of-function allele did not elevate their risk of combined any-cause death and other adverse cardiac outcomes, including major bleeding, 12 months after PCI; and that giving clopidogrel to the genotype-guided group lowered the risk of minor bleeding.

Dr. Claassens and coauthors noted that since the Netherlands trial was designed in 2011, the development of newer-generation stents has considerably lowered rates of thrombotic events after acute coronary syndromes. “With the lower-than-anticipated incidence of the primary combined outcome in our trial, the prespecified noninferiority margin was wider relative to the incidence than originally expected,” they said. While the primary combined outcome was 21% higher than the incidence in the standard-treatment group at the upper end of the 95% confidence interval, the incidence was 11% higher in the standard-treatment group at the observed upper end of the 95% CI. This “gives stronger support to the conclusion that genotype-guided P2Y₁₂ treatment is noninferior to standard treatment for the occurrence of thrombotic events,” Dr. Claassens and coauthors said.

The study report noted a number of limitations, including that more polymorphisms of the CyP2C19 gene may be linked to increased thrombotic or bleeding risk. “Therefore, our strategy based solely on the CYP2C19 genotype may not be the most useful strategy for some patients,” Dr. Claassens and coauthors said.

POPular Genetics received funding from the Netherlands Organization for Health Research and Development (ZonMw). Dr. Claassens receives grants from ZonMw and non-financial support from Spartan Biosciences.

SOURCE: Claassens DMF, et al. N Engl J. Med. Published online September 3, doi.org/10.1016/S0140-6736(19)31996-8.

A number of medications commonly prescribed by rheumatologists may interact with cannabidiol oil, investigators at the Imperial College Healthcare NHS Trust, London, reported.

“Patients are increasingly requesting information concerning the safety of CBD oil,” Taryn Youngstein, MD, and associates said in letter to the editor in Rheumatology, but current guidelines on the use of medical cannabis do “not address the potential interactions between CBD oil and medicines frequently used in the rheumatology clinic.”

The most important potential CBD interaction, they suggested, may be with corticosteroids. Hydrocortisone and prednisolone both inhibit the cytochrome P450 enzyme CYP3A, but CBD is a potent inhibitor of CYP3A, so “concomitant use may decrease glucocorticoid clearance and increase risk of systemic [corticosteroid] side effects,” the investigators wrote.

CBD also is known to inhibit the cytochrome P450 isozymes CYP2C9, CYP2D6, CYP2C19, CYP3A4, and CYP1A2, which, alone or in combination, are involved in the metabolization of naproxen, tramadol, amitriptyline, and tofacitinib (Xeljanz), according to a literature search done via the college’s medicine information department that also used the British National Formulary and the Natural Medicines online interaction checker.

The Janus kinase inhibitor tofacitinib is included among the possible interactions, but the other Food and Drug Administration–approved JAK inhibitor, baricitinib (Olumiant), is primarily metabolized by the kidneys and should not have significant interaction with CBD, Dr. Youngstein and associates said. Most of the conventional synthetic and biologic disease-modifying antirheumatic drugs, including methotrexate, hydroxychloroquine, adalimumab (Humira), and abatacept (Orencia), also are expected to be relatively free from CBD interactions.

This first published report on interactions between CBD oil and common rheumatology medications “highlights the importance of taking comprehensive drug histories, by asking directly about drugs considered alternative medicines and food supplements,” they said.

The investigators declared no conflicts of interest, and there was no specific funding for the study.

[email protected]

SOURCE: Wilson-Morkeh H et al. Rheumatology. 2019 July 29. doi: 10.1093/rheumatology/kez304.

A number of medications commonly prescribed by rheumatologists may interact with cannabidiol oil, investigators at the Imperial College Healthcare NHS Trust, London, reported.

“Patients are increasingly requesting information concerning the safety of CBD oil,” Taryn Youngstein, MD, and associates said in letter to the editor in Rheumatology, but current guidelines on the use of medical cannabis do “not address the potential interactions between CBD oil and medicines frequently used in the rheumatology clinic.”

The most important potential CBD interaction, they suggested, may be with corticosteroids. Hydrocortisone and prednisolone both inhibit the cytochrome P450 enzyme CYP3A, but CBD is a potent inhibitor of CYP3A, so “concomitant use may decrease glucocorticoid clearance and increase risk of systemic [corticosteroid] side effects,” the investigators wrote.

CBD also is known to inhibit the cytochrome P450 isozymes CYP2C9, CYP2D6, CYP2C19, CYP3A4, and CYP1A2, which, alone or in combination, are involved in the metabolization of naproxen, tramadol, amitriptyline, and tofacitinib (Xeljanz), according to a literature search done via the college’s medicine information department that also used the British National Formulary and the Natural Medicines online interaction checker.

The Janus kinase inhibitor tofacitinib is included among the possible interactions, but the other Food and Drug Administration–approved JAK inhibitor, baricitinib (Olumiant), is primarily metabolized by the kidneys and should not have significant interaction with CBD, Dr. Youngstein and associates said. Most of the conventional synthetic and biologic disease-modifying antirheumatic drugs, including methotrexate, hydroxychloroquine, adalimumab (Humira), and abatacept (Orencia), also are expected to be relatively free from CBD interactions.

This first published report on interactions between CBD oil and common rheumatology medications “highlights the importance of taking comprehensive drug histories, by asking directly about drugs considered alternative medicines and food supplements,” they said.

The investigators declared no conflicts of interest, and there was no specific funding for the study.

[email protected]

SOURCE: Wilson-Morkeh H et al. Rheumatology. 2019 July 29. doi: 10.1093/rheumatology/kez304.

A number of medications commonly prescribed by rheumatologists may interact with cannabidiol oil, investigators at the Imperial College Healthcare NHS Trust, London, reported.

“Patients are increasingly requesting information concerning the safety of CBD oil,” Taryn Youngstein, MD, and associates said in letter to the editor in Rheumatology, but current guidelines on the use of medical cannabis do “not address the potential interactions between CBD oil and medicines frequently used in the rheumatology clinic.”

The most important potential CBD interaction, they suggested, may be with corticosteroids. Hydrocortisone and prednisolone both inhibit the cytochrome P450 enzyme CYP3A, but CBD is a potent inhibitor of CYP3A, so “concomitant use may decrease glucocorticoid clearance and increase risk of systemic [corticosteroid] side effects,” the investigators wrote.

CBD also is known to inhibit the cytochrome P450 isozymes CYP2C9, CYP2D6, CYP2C19, CYP3A4, and CYP1A2, which, alone or in combination, are involved in the metabolization of naproxen, tramadol, amitriptyline, and tofacitinib (Xeljanz), according to a literature search done via the college’s medicine information department that also used the British National Formulary and the Natural Medicines online interaction checker.

The Janus kinase inhibitor tofacitinib is included among the possible interactions, but the other Food and Drug Administration–approved JAK inhibitor, baricitinib (Olumiant), is primarily metabolized by the kidneys and should not have significant interaction with CBD, Dr. Youngstein and associates said. Most of the conventional synthetic and biologic disease-modifying antirheumatic drugs, including methotrexate, hydroxychloroquine, adalimumab (Humira), and abatacept (Orencia), also are expected to be relatively free from CBD interactions.

This first published report on interactions between CBD oil and common rheumatology medications “highlights the importance of taking comprehensive drug histories, by asking directly about drugs considered alternative medicines and food supplements,” they said.

The investigators declared no conflicts of interest, and there was no specific funding for the study.

[email protected]

SOURCE: Wilson-Morkeh H et al. Rheumatology. 2019 July 29. doi: 10.1093/rheumatology/kez304.

For too many of us, a good night’s sleep is a rare occurrence. Lack of quality sleep has profound negative effects on our health, safety, and wellbeing. An estimated 50 to 70 million Americans have sleep disturbances, including 10% to 17% of men and 3% to 9% of women with moderate to severe obstructive sleep apnea (OSA).¹ Not only is OSA highly prevalent, 82% to 93% of individuals with moderate to severe OSA are unaware they have it, and it remains undiagnosed.²

OSA is a potentially serious medical disorder affecting the heart, brain, and metabolism. These physiological changes negatively impact public safety, occupational and academic achievement, and even mortality.

This Cleveland Clinic Journal of Medicine supplement presents a state-of-the-art review of OSA, including the health and societal consequences of OSA and current treatment options. The goal of this publication is to inform and educate healthcare providers from all backgrounds and levels of care who are interested in improving patient outcomes through attention to sleep medicine.

Because OSA is prevalent and underdiagnosed, Jessica Vensel Rundo, MD, MS, reviews the symptoms of OSA, clinical presentation, and the readily available, effective screening tools for detecting sleep apnea. Greater awareness and screening for sleep disturbances informs the need for further diagnostic tests such as laboratory polysomnography and home sleep apnea testing.

The link between OSA and the heart is presented by Reena Mehra, MD, MS, with an overview of the physiology of sleep-heart interactions and the association of OSA and cardiovascular health. Dr. Mehra also reviews central sleep apnea and discusses 2 newer therapies for it: adaptive servoventilation and phrenic nerve stimulation.

Beyond heart health, OSA also adversely affects quality of life, safety, and other important health factors. Harneet Walia, MD, discusses consequences of sleep apnea such as daytime sleepiness, fatigue, drowsy driving, depression, metabolic diseases, and cognitive impairment.

Several treatment options exist for patients diagnosed with OSA. Positive airway pressure (PAP) therapy is the gold standard for treatment of OSA. Colleen G. Lance, MD, reviews and presents case scenarios about the efficacy of PAP therapy, features of continuous PAP therapy, and innovative strategies to improve adherence to therapy.

In addition to PAP therapy, there are alternative treatments for OSA that may benefit some patients.  Tina Waters, MD, considers alternatives to PAP therapy, such as lifestyle changes, expiratory PAP therapy, oral appliances, upper airway surgery, and hypoglossal nerve stimulation.

I hope you enjoy this supplement and find it useful to improving the health and quality-of-life outcomes of patients in your care.

For too many of us, a good night’s sleep is a rare occurrence. Lack of quality sleep has profound negative effects on our health, safety, and wellbeing. An estimated 50 to 70 million Americans have sleep disturbances, including 10% to 17% of men and 3% to 9% of women with moderate to severe obstructive sleep apnea (OSA).¹ Not only is OSA highly prevalent, 82% to 93% of individuals with moderate to severe OSA are unaware they have it, and it remains undiagnosed.²

OSA is a potentially serious medical disorder affecting the heart, brain, and metabolism. These physiological changes negatively impact public safety, occupational and academic achievement, and even mortality.

This Cleveland Clinic Journal of Medicine supplement presents a state-of-the-art review of OSA, including the health and societal consequences of OSA and current treatment options. The goal of this publication is to inform and educate healthcare providers from all backgrounds and levels of care who are interested in improving patient outcomes through attention to sleep medicine.

Because OSA is prevalent and underdiagnosed, Jessica Vensel Rundo, MD, MS, reviews the symptoms of OSA, clinical presentation, and the readily available, effective screening tools for detecting sleep apnea. Greater awareness and screening for sleep disturbances informs the need for further diagnostic tests such as laboratory polysomnography and home sleep apnea testing.

The link between OSA and the heart is presented by Reena Mehra, MD, MS, with an overview of the physiology of sleep-heart interactions and the association of OSA and cardiovascular health. Dr. Mehra also reviews central sleep apnea and discusses 2 newer therapies for it: adaptive servoventilation and phrenic nerve stimulation.

Beyond heart health, OSA also adversely affects quality of life, safety, and other important health factors. Harneet Walia, MD, discusses consequences of sleep apnea such as daytime sleepiness, fatigue, drowsy driving, depression, metabolic diseases, and cognitive impairment.

Several treatment options exist for patients diagnosed with OSA. Positive airway pressure (PAP) therapy is the gold standard for treatment of OSA. Colleen G. Lance, MD, reviews and presents case scenarios about the efficacy of PAP therapy, features of continuous PAP therapy, and innovative strategies to improve adherence to therapy.

In addition to PAP therapy, there are alternative treatments for OSA that may benefit some patients.  Tina Waters, MD, considers alternatives to PAP therapy, such as lifestyle changes, expiratory PAP therapy, oral appliances, upper airway surgery, and hypoglossal nerve stimulation.

I hope you enjoy this supplement and find it useful to improving the health and quality-of-life outcomes of patients in your care.

For too many of us, a good night’s sleep is a rare occurrence. Lack of quality sleep has profound negative effects on our health, safety, and wellbeing. An estimated 50 to 70 million Americans have sleep disturbances, including 10% to 17% of men and 3% to 9% of women with moderate to severe obstructive sleep apnea (OSA).¹ Not only is OSA highly prevalent, 82% to 93% of individuals with moderate to severe OSA are unaware they have it, and it remains undiagnosed.²

OSA is a potentially serious medical disorder affecting the heart, brain, and metabolism. These physiological changes negatively impact public safety, occupational and academic achievement, and even mortality.

This Cleveland Clinic Journal of Medicine supplement presents a state-of-the-art review of OSA, including the health and societal consequences of OSA and current treatment options. The goal of this publication is to inform and educate healthcare providers from all backgrounds and levels of care who are interested in improving patient outcomes through attention to sleep medicine.

Because OSA is prevalent and underdiagnosed, Jessica Vensel Rundo, MD, MS, reviews the symptoms of OSA, clinical presentation, and the readily available, effective screening tools for detecting sleep apnea. Greater awareness and screening for sleep disturbances informs the need for further diagnostic tests such as laboratory polysomnography and home sleep apnea testing.

The link between OSA and the heart is presented by Reena Mehra, MD, MS, with an overview of the physiology of sleep-heart interactions and the association of OSA and cardiovascular health. Dr. Mehra also reviews central sleep apnea and discusses 2 newer therapies for it: adaptive servoventilation and phrenic nerve stimulation.

Beyond heart health, OSA also adversely affects quality of life, safety, and other important health factors. Harneet Walia, MD, discusses consequences of sleep apnea such as daytime sleepiness, fatigue, drowsy driving, depression, metabolic diseases, and cognitive impairment.

Several treatment options exist for patients diagnosed with OSA. Positive airway pressure (PAP) therapy is the gold standard for treatment of OSA. Colleen G. Lance, MD, reviews and presents case scenarios about the efficacy of PAP therapy, features of continuous PAP therapy, and innovative strategies to improve adherence to therapy.

In addition to PAP therapy, there are alternative treatments for OSA that may benefit some patients.  Tina Waters, MD, considers alternatives to PAP therapy, such as lifestyle changes, expiratory PAP therapy, oral appliances, upper airway surgery, and hypoglossal nerve stimulation.

I hope you enjoy this supplement and find it useful to improving the health and quality-of-life outcomes of patients in your care.

Multiple sclerosis (MS) is one of the leading causes of disability and many efforts have been implemented to help expediate diagnosis and initiate early, effective treatment. With rapidly changing guidelines and treatment indications, it can be difficult discerning when to start a disease-modifying therapy in the early spectrum of MS, such as clinically and radiologically isolated syndrome; how to discuss MS management in women of childbearing age; or how to use the new guidelines to confirm an MS diagnosis. 

Click here to read the supplement and earn 1 AMA Category 1 Credit ^TM by learning about these topics.

Click here to read the supplement. 

Multiple sclerosis (MS) is one of the leading causes of disability and many efforts have been implemented to help expediate diagnosis and initiate early, effective treatment. With rapidly changing guidelines and treatment indications, it can be difficult discerning when to start a disease-modifying therapy in the early spectrum of MS, such as clinically and radiologically isolated syndrome; how to discuss MS management in women of childbearing age; or how to use the new guidelines to confirm an MS diagnosis. 

Click here to read the supplement and earn 1 AMA Category 1 Credit ^TM by learning about these topics.

Click here to read the supplement. 

Multiple sclerosis (MS) is one of the leading causes of disability and many efforts have been implemented to help expediate diagnosis and initiate early, effective treatment. With rapidly changing guidelines and treatment indications, it can be difficult discerning when to start a disease-modifying therapy in the early spectrum of MS, such as clinically and radiologically isolated syndrome; how to discuss MS management in women of childbearing age; or how to use the new guidelines to confirm an MS diagnosis. 

Click here to read the supplement and earn 1 AMA Category 1 Credit ^TM by learning about these topics.

Click here to read the supplement.