Boosting Female Sexual Response by RECONNECTing the Dots No abstract available

Bremelanotide for the Treatment of Hypoactive Sexual Desire Disorder: Two Randomized Phase 3 Trials OBJECTIVE: To evaluate the safety and efficacy of bremelanotide for the treatment of premenopausal women with hypoactive sexual desire disorder. METHODS: Two identical phase 3, randomized, double-blind, placebo-controlled, multicenter clinical trials (RECONNECT) evaluated the safety and efficacy of bremelanotide 1.75 mg administered subcutaneously as needed in premenopausal women with hypoactive sexual desire disorder. Patients were randomized 1:1 to 24 weeks of treatment with bremelanotide or placebo. Sample size was estimated based on simulations from key endpoints in patients with hypoactive sexual desire disorder from a prior trial. Coprimary efficacy endpoints were change from baseline to end-of-study in the Female Sexual Function Index–desire domain score and Female Sexual Distress Scale–Desire/Arousal/Orgasm item 13. RESULTS: Study 301 began on January 7, 2015, and concluded on July 26, 2016. Study 302 began on January 28, 2015, and concluded on August 4, 2016. Of the 1,267 women randomized, 1,247 and 1,202 were in the safety and efficacy (modified intent-to-treat) populations, respectively. Most participants were white (85.6%), from U.S. sites (96.6%), and had a mean age of 39 years. From baseline to end-of-study, women taking bremelanotide had statistically significant increases in sexual desire (study 301: 0.30, P<.001; study 302: 0.42, P<.001; integrated studies 0.35, P<.001) and statistically significant reductions in distress related to low sexual desire (study 301: −0.37, P<.001; study 302: −0.29, P=.005; integrated studies −0.33, P<.001) compared with placebo. Patients taking bremelanotide experienced more nausea, flushing, and headache (10% or more in both studies) compared with placebo. CONCLUSIONS: Both studies demonstrated that bremelanotide significantly improved sexual desire and related distress in premenopausal women with hypoactive sexual desire disorder. The safety profile was favorable. Most treatment-emergent adverse events were related to tolerability and the majority were mild or moderate in intensity. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT02333071 (study 301) and NCT02338960 (study 302). FUNDING SOURCE: Palatin Technologies, Inc., and AMAG Pharmaceuticals, Inc.

Long-Term Safety and Efficacy of Bremelanotide for Hypoactive Sexual Desire Disorder OBJECTIVE: To evaluate the long-term safety and efficacy of bremelanotide as treatment for hypoactive sexual desire disorder in premenopausal women. METHODS: Women who completed the 24-week double-blind core phase of RECONNECT, composed of two parallel phase 3 trials (301 and 302) examining the safety and efficacy of bremelanotide compared with placebo in premenopausal women with hypoactive sexual desire disorder, could enroll in the 52-week open-label extension, provided they had not experienced serious adverse events during the core phase. Efficacy was assessed using the coprimary endpoints from the core phase, and all adverse events were collected during the open-label extension. All statistical analyses were descriptive. RESULTS: The study 301 open-label extension began on July 17, 2015, and concluded on July 13, 2017; the study 302 open-label extension began on October 5, 2015, and concluded on June 29, 2017. Of the 856 eligible patients who completed the core phase, 684 elected to participate in the open-label extension, and 272 completed it. The most common treatment-emergent adverse events considered related to study drug were nausea (40.4%), flushing (20.6%), and headache (12.0%), and the only severe treatment-emergent adverse event experienced by more than one participant in both studies was nausea during the open-label extension. The change in Female Sexual Function Index–desire domain score and Female Sexual Distress Scale–Desire/Arousal/Orgasm item 13 from baseline to end of the open-label extension ranged from 1.25 to 1.30 and −1.4 to −1.7, respectively, for patients who received bremelanotide during the core phase, and 0.70–0.77 and −0.9, respectively, for patients who received placebo during the core phase. CONCLUSION: During the 52-week open-label extension of RECONNECT, no new safety signals were observed, and premenopausal women treated with bremelanotide exhibited sustained improvements in hypoactive sexual desire disorder symptoms. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT02333071 (study 301) and NCT02338960 (study 302). FUNDING SOURCE: Palatin Technologies, Inc., and AMAG Pharmaceuticals, Inc.

Fertility Fraud, Legal Firsts, and Medical Ethics No abstract available

Methadone, Buprenorphine, or Detoxification for Management of Perinatal Opioid Use Disorder: A Cost-Effectiveness Analysis OBJECTIVE: To estimate whether methadone, buprenorphine, or detoxification treatment is the most cost-effective approach to the management of opioid use disorder (OUD) during pregnancy. METHODS: We created a decision analytic model that compared the cost effectiveness (eg, the marginal cost of the strategy in U.S. dollars divided by the marginal effectiveness of the strategy, measured in quality-adjusted life-years [QALYs]) of initiation of methadone, buprenorphine, or detoxification in treatment of OUD during pregnancy. Probabilities, costs, and utilities were estimated from the existing literature. Incremental cost-effective ratios for each strategy were calculated, and a ratio of $100,000 per QALY was used to define cost effectiveness. One-way sensitivity analyses and a Monte Carlo probabilistic sensitivity analysis were performed. RESULTS: Under base assumptions, initiation of buprenorphine was more effective at a lower cost than either methadone or detoxification and thus was the dominant strategy. Buprenorphine was no longer cost effective if the cost of methadone was 8% less than the base-case estimate ($1,646/month) or if the overall costs of detoxification were 121% less than the base-case estimate for the detoxification cost multiplier, which was used to increase the values of both inpatient and outpatient management of detoxification by a factor of 2. Monte Carlo analyses revealed that buprenorphine was the cost-effective strategy in 70.5% of the simulations. Direct comparison of buprenorphine with methadone demonstrated that buprenorphine was below the incremental cost-effective ratio in 95.1% of simulations; direct comparison between buprenorphine and detoxification demonstrated that buprenorphine was below the incremental cost-effective ratio in 45% of simulations. CONCLUSION: Under most circumstances, we estimate that buprenorphine is the cost-effective strategy when compared with either methadone or detoxification as treatment for OUD during pregnancy. Nonetheless, the fact that buprenorphine was not the cost-effective strategy in almost one out of three of simulations suggests that the robustness of our model may be limited and that further evaluation of the cost-effective approach to the management of OUD during pregnancy is needed.

Decreasing Opioid Use Postpartum: A Quality Improvement Initiative OBJECTIVE: To estimate the effects of an inpatient initiative to decrease opioid use among women admitted to labor and delivery. METHODS: We created a multimodal pain power plan with standard therapeutic postpartum activity goals rather than pain goals, tiered order sets with scheduled administration of nonsteroidal antiinflammatory drugs (NSAIDs), and embedded changes into the electronic health record. Before the multimodal pain power plan launch, pain was assessed on a 10-point scale; women received NSAIDs for pain levels of 3 or less and opioids for pain levels higher than 3. For this analysis, we included women who delivered at 5 hospitals in the 10 months before and 12 months after the multimodal pain power plan launch. Women with prior substance use disorder or complicated deliveries were excluded and we stratified analyses into women who delivered vaginally compared with by cesarean. Opioid use was converted to morphine milligram equivalent (MME). Women rated pain control in 24-hour blocks using individually ascertained cutoffs. A multivariable regression analysis was performed, and adjusted odds ratios are reported. RESULTS: We compared the 6,892 women who delivered 10 months before the pain power plan launch to the 7,527 who delivered in the 12 months after the launch. The mean cohort age was 29.6±6.0 years; the majority (75%) were white. Risk of opioid use decreased by 26% among women who delivered vaginally (risk ratio [RR] 0.74; 95% CI [0.68, 0.81]) and 18% among women who delivered by cesarean (RR 0.82; 95% CI [0.72, 0.92]). Among women who received opioids, mean MME use decreased 21% (RR 0.79; 95% CI [0.70, 0.88]) and 54% (RR 0.46; 95% CI [0.35, 0.61]) in the vaginal and cesarean delivery groups, respectively. Fewer women reported acceptable pain levels, with decreases of 82–69% (P<.01) and 82–74% (P<.01) in the vaginal and cesarean delivery groups, respectively. Within the postlaunch cesarean delivery group, women also reported that they were less likely to have their pain well controlled on the Hospital Consumer Assessment of Healthcare Providers and Systems questionnaires (82% vs 62%, P <.01). CONCLUSION: A standardized multimodal pain power plan reduced opioid use among a large cohort of women admitted to labor and delivery in Central Texas. Despite meeting functional goals, some women reported increased pain during their hospital stay.

Telemedicine Companies Providing Prescription-Only Medications: Pros, Cons, and Proposed Guidelines In the past few years, there has been a significant increase in the number of direct-to-consumer telehealth companies offering prescription medications to women. Leveraging technology, these companies have the potential to improve access to care and ensure that women have access to prescription-only medications in a convenient fashion. However, it is important to ensure that they are doing so in a safe, patient-centered way that observes evidence-based prescribing guidelines. In this article, we discuss the pros and cons of direct-to-consumer telehealth companies offering prescription medicine and suggest several guidelines to ensure that women are being cared for in an appropriate way.

Development and Validation of a Machine Learning Algorithm for Predicting Response to Anticholinergic Medications for Overactive Bladder Syndrome OBJECTIVE: To develop and externally validate a prediction model for anticholinergic response in patients with overactive bladder (OAB). METHODS: A machine learning model to predict the likelihood of anticholinergic treatment failure was constructed using a retrospective data set (n=559) of female patients with OAB who were treated with anticholinergic medications between January 2010 and December 2017. Treatment failure was defined as less than 50% improvement in frequency, urgency, incontinence episodes, and nocturia, and the patient's subjective impression of symptomatic relief. Patients were stratified by age (younger than 40 years, 40–60 years, and older than 60 years), and number of previously failed medications. K-fold stratified cross-validation was performed on each stratum using machine learning algorithms. Of these, the random forest model was the most accurate. This model was refined using internal cross validation within each stratum. The area under the curve (AUC) was calculated for each stratum and used to identify the optimal operating points for prediction of treatment failure. The random forest model was then externally validated using a prospectively collected data set (n=82) of women treated with anticholinergic medications at a different clinical site between January 2018 and December 2018. RESULTS: The global accuracy of the final model was 80.3% (95% CI 79.1–81.3), and the AUC was 0.77 (95% CI 0.74–0.79). Using the external validation data set, the model's sensitivity and specificity was 80.4% (95% CI 66.5–89.7%) and 77.4% (95% CI 58.6–89.7%), respectively. The model performed best in women aged younger than 40 years (AUC 0.84, 95% CI 0.81–0.84) and worst in women aged older than 60 years who had previously failed medication (AUC 0.71, 95% CI 0.67–0.75). CONCLUSION: Our externally validated machine learning prediction model can predict anticholinergic treatment failure during the standard 3-month treatment trial period with greater than 80% accuracy. The model can be accessed at https://oabweb.herokuapp.com/app/pre/.

Providing Patient-Centered Perinatal Care for Transgender Men and Gender-Diverse Individuals: A Collaborative Multidisciplinary Team Approach BACKGROUND: Little is documented about the experiences of pregnancy for transgender and gender-diverse individuals. There is scant clinical guidance for providing prepregnancy, prenatal, intrapartum, and postpartum care to transgender and gender-diverse people who desire pregnancy. CASE: Our team provided perinatal care to a 20-year-old transgender man, which prompted collaborative advocacy for health care systems change to create gender-affirming patient experiences in the perinatal health care setting. CONCLUSION: Systems-level and interpersonal-level interventions were adopted to create gender-affirming and inclusive care in and around pregnancy. Basic practices to mitigate stigma and promote gender-affirming care include staff trainings and query and use of appropriate name and pronouns in patient interactions and medical documentation. Various factors are important to consider regarding testosterone therapy for transgender individuals desiring pregnancy.

Association Between Stillbirth at 23 Weeks of Gestation or Greater and Severe Maternal Morbidity OBJECTIVE: To estimate whether stillbirth at 23 weeks of gestation or more is associated with increased risk of severe maternal morbidity compared with live birth, when stratified by maternal comorbidities. METHODS: This retrospective cohort study used International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) diagnosis and procedure codes within the Healthcare Cost and Utilization Project's Florida State Inpatient Database. The first delivery of female Florida residents aged 13–54 years old from 2005 to 2014 was included. The exposure was an ICD-9-CM code of stillbirth at 23 weeks of gestation or more; the control was an ICD-9-CM code of singleton live birth. Deliveries were stratified by the presence of 1 or more conditions within a well-validated maternal morbidity composite using ICD-9-CM codes during delivery hospitalization. The primary outcome was an ICD-9-CM diagnosis or procedure code during delivery hospitalization of any indices within the Centers for Disease Control and Prevention's severe maternal morbidity composite. Multivariable analyses adjusted for maternal sociodemographic factors and delivery mode to compare outcomes after stillbirth with live-birth delivery. RESULTS: Nine thousand five hundred twenty-three women who delivered stillborn fetuses and 1,353,044 with liveborn neonates were included. Among 6,590 stillbirths and 935,913 live births without maternal comorbidities, severe maternal morbidity was significantly more common during stillbirth delivery (n=345 [5.2%]), corresponding to a seven-fold increased risk compared with live birth (n=8,318 [0.9]; adjusted odds ratio [aOR] 7.05 [95% CI 6.27–7.93]). Among 2,933 stillbirths and 417,131 live births with maternal comorbidities, severe maternal morbidity was significantly more common during stillbirth delivery (n=390 [13.3%]): the risk was more than six-fold higher comparatively (n=11,122 [2.7%]; aOR 6.21 [95% CI 5.54–6.96]). Most maternal comorbidities were individually associated with higher risk of severe maternal morbidity during stillbirth compared with live-birth delivery. CONCLUSION: Though severe maternal morbidity is overall uncommon, delivering a stillborn fetus 23 weeks of gestation or greater is associated with increased likelihood of severe maternal morbidity, particularly among women with comorbidities, suggesting health care providers must be vigilant about severe maternal morbidity during stillbirth delivery.