bluuebunny/crossref_metadata_2025 huggingface dataset:
Safety of AG200-15, an Investigational Transdermal Patch, in Three Phase 3 Studies [1J]
Authors: Nelson Anita L. , Kaunitz Andrew M. , Kroll Robin , Simon James A. , Castano Paula M. , Garner Elizabeth I. O.
Published: May 2019

INTRODUCTION:

AG200-15 (Twirla®) is an investigational transdermal contraceptive delivery system (TCDS), which delivers daily exposure of approximately 120 µg of levonorgestrel and 30Î1/4 g of ethinyl estradiol. We report the safety from three Phase 3 studies - the SECURE (ATI-CL23) study, ATI-CL12, and ATI-CL-13.

METHODS:

SECURE was a single-arm, 13-cycle, open-label study conducted in 2014-2016. ATI-CL12 (13-cycles) and ATI-CL13 (6-cycles) were conducted in 2010-2011 and were open-label, randomized, active-controlled (an approved oral contraceptive (OC)) safety and efficacy studies. Subjects reported all treatment emergent adverse events (TEAEs) and serious adverse events (SAEs). TEAEs were defined as adverse events with an onset date on or after the first patch application through Day 28 of the subject's final treatment cycle. The results reported represent combined safety data.

RESULTS:

For AG200-15 in all studies combined, 54% of 3,481 subjects had at least one TEAE, 26% had at least one study drug-related TEAE, 5% had TEAEs of severe intensity, and 11% had TEAEs resulting in study drug discontinuation. Fewer than 2 percent of subjects (n=56) had SAEs, and 0.5% (n=18) had study drug-related SAEs. The SAEs occurring in >2 subjects were cholelithiasis (n=4), deep vein thrombosis (3), pulmonary embolism (3), and depression (3). No deaths were reported. The most common TEAEs (≥-2%) included nasopharyngitis (5.7%), upper respiratory tract infection (4.5%), nausea (4.3%), headache (3.6%), and urinary tract infections (3.5%).

CONCLUSION:

The percentages of TEAEs and SAEs were generally similar across the Phase 3 studies. The adverse event profile of AG200-15 appears to be similar to approved OCs.
Early Postpartum Perineal Repair or C-Section Suture Removal Reduces Pain Without Wound Complications [7J]
Authors: Chan Anthony K.
Published: May 2019

INTRODUCTION:

To describe postpartum sutures or staples related pain resolution and wound healing in patients with perineal repair or C-section who underwent early sutures or staples removal.

METHODS:

All patients in an outpatient obstetric clinic who delivered between June 1, 2016 to June 30, 2017 and received sutures or staples in wound closure were invited to participate in this prospective observational study of early sutures or staples removal by day four to seven postpartum. Pain scores were recorded for activities of standing, walking, and sitting from a preset scale of zero to five before and after sutures or staples removal. With six weeks postpartum visit, wound healing was evaluated. Pictures were taken from those who consented.

RESULTS:

A total of 68 participants were included in this prospective observational study. 52 participants underwent vaginal deliveries with perineal repair and 16 participants underwent C-sections prior to inclusion of this study. When pain scores were three or above, there was reduction of pain scores of two or more. Excellent wound healing was observed at six-week postpartum visits.

CONCLUSION:

Early sutures or staples removal in postpartum patients reduced pain without compromising wound healing. This suggests the utility of early sutures or staples removal in postpartum patients can reduce analgesic use and improve quality of life.
Elagolix Treatment in Women With Uterine Fibroids: Secondary, 6-Month, Phase 3 Efficacy Results [11J]
Authors: Bradley Linda D. , Feinberg Eve C. , Liu Ran , Owens Charlotte D. , Rodriguez-Ginorio Henry , Simon James A.
Published: May 2019

INTRODUCTION:

Objective was to evaluate the effect of elagolix with add-back, as compared with placebo, on menstrual blood loss (MBL), suppression of bleeding, and hemoglobin concentration in women with heavy menstrual bleeding (HMB, >80mL/cycle MBL) associated with uterine fibroids (UF).

METHODS:

These were two replicate, investigational, double-blind, randomized, placebo-controlled, 6-month (M), phase 3 studies (Elaris UF-1/Elaris UF-2) where patients were randomized 1:1:2 to placebo, elagolix 300mg twice daily (BID) alone and elagolix 300mg BID in combination with 1mg estradiol (E2)/0.5 mg norethindrone acetate (NETA) once daily add-back. Patients were premenopausal, 18-51 year-old women. Secondary efficacy endpoints included change from baseline in MBL volume at M1, M3, M6 and Final Month, suppression of bleeding (no bleeding days, spotting allowed) at Final Month, and M6 hematological improvement. Endometrial biopsies were performed at baseline and M6. IRB approval obtained.

RESULTS:

In Elaris UF-1, 412 women were randomized/treated and 328 completed treatment. For Elaris UF-1, elagolix+E2/NETA reduced MBL volume from baseline at M1, M3, M6 and Final Month (Final Month mean [SE] MBL change from baseline: elagolix+E2/NETA=-176.7 mL [10.4], P<0.001; placebo=0.8 [14.9]). A greater percentage of elagolix+E2/NETA-treated women had suppression of bleeding at Final Month compared with placebo (elagolix+E2/NETA=56.8%, P<0.001; placebo=4.4%). The percentage of women with a baseline ≤10.5 g/dL and increase from baseline >2 g/dL at M6 in hemoglobin concentration was significantly greater for elagolix+E2/NETA compared with placebo (elagolix+E2/NETA=61.5%, P<0.001; placebo=16.1%). There was no endometrial hyperplasia or malignancy among elagolix-treated women. Elaris UF-2 results were similar.

CONCLUSION:

Elagolix+E2/NETA treatment met all ranked secondary endpoints including reduced MBL volume, suppression of bleeding, and increased hematologic parameters in women with HMB associated with UF.
Elagolix Versus Laparoscopic Surgery for Treatment of Pain Due to Endometriosis: A Cost-Effectiveness Analysis [12J]
Authors: Movilla Peter
Published: May 2019

INTRODUCTION:

The objective was to assess the cost-effectiveness Elagolix versus laparoscopic conservative surgery as the primary treatment of moderate to severe pain due to endometriosis.

METHODS:

A Markov model was developed comparing primary treatment with Elagolix to primary laparoscopic conservative surgery for patients with moderate to severe pain due to endometriosis. Clinical and surgical data were obtained from published literature. Medical costs were obtained utilizing contemporary charges for standard treatments. The medical and financial outcomes were evaluated from time of patient presentation with moderate to severe pain, until time of patient death. A sensitivity analysis was performed to evaluate the significance of various medical and financial parameters designated within the model on disease specific outcomes. Main outcome was measured in quality-adjusted life years (QALYs) and costs from a national healthcare perspective.

RESULTS:

Laparoscopic conservative surgery was a strongly dominant treatment strategy when compared to Elagolix for the purpose of primary treatment for moderate to severe pain from endometriosis based on our Monte-Carlo microsimulation cost-effectiveness analysis. A second order probabilistic sensitivity analysis demonstrated that laparoscopic conservative surgery for endometriosis is cost-effective when compared to Elagolix for primary treatment of moderate to severe pain from endometriosis, with a willingness to pay threshold of $410.35 per QALY over all ranges of varying utilities and costs utilized.

CONCLUSION:

From a national healthcare perspective, laparoscopic conservative surgery for endometriosis is more cost-effective than Elagolix for the primary treatment of moderate to severe pain from endometriosis that has been refractory to standard medical care.
Impact of Elagolix on Quality of Life Among Endometriosis Patients: A Pooled Analysis of 2 Phase III Clinical Trials [13J]
Authors: Taylor Hugh S. , Soliman Ahmed M. , Palac Hannah , Surrey Eric S.
Published: May 2019

INTRODUCTION:

Endometriosis-associated symptoms are associated with reduction in health-related quality of life (HRQL). This analysis evaluated the impact of Elagolix, an oral gonadotrophin releasing-hormone antagonist, on the HRQL of women with moderate to severe pain associated with endometriosis.

METHODS:

Data were pooled from two phase III randomized, placebo-controlled trials of elagolix (150mg once daily “Elagolix QD” or 200 mg twice daily “Elagolix BID”) in premenopausal women with moderate-to-severe endometriosis-associated pain. The Endometriosis Health profile (EHP-30), HRQL questionnaire was administered at baseline and months 1, 3 and 6 of treatment. Changes in the 5 core scales (pain, control and powerlessness, social support, emotional well-being, and self-image) and sexual intercourse modular scale scores of EHP-30 from baseline to month 3 and 6 were compared between each Elagolix dose and placebo using ANCOVA models that controlled for baseline scores.

RESULTS:

Final sample included 1686 patients. Both doses of elagolix exhibited a significantly greater reduction in all 6 scale scores than placebo (lower scores indicate better HRQL) at Month 3 in a dose-dependent fashion (pain: -18.49, -26.79, -35.59; control and powerlessness:-24.86, -32.81, -42.28; emotional well-being:-13.67, -17.75, -21.15; social support: -12.54, -18.0, -24.14; self-image:-11.16, -16.54, -21.08 and sexual intercourse: -13.54, -17.22 and -25.85 for placebo, Elagolix QD and Elagolix BID respectively; P <0.05 for all Elagolix group comparisons to placebo). Larger reductions were also observed for Elagolix groups at month 6 which were statistically significant for all scales except for self-image and sexual intercourse.

CONCLUSION:

Elagolix significantly improves HRQL among women with moderate to severe pain associated with endometriosis.
Intrauterine Device Perforation and Adhesion Formation [14J]
Authors: Narayanamoorthy Sujatha , Christensen Ashley Rachelle , Apostol Radu
Published: May 2019

INTRODUCTION:

The intrauterine device (IUD) is one of the most popular methods of contraception used globally. There are 2 classes of IUDs available worldwide: metal containing and levonorgestrel releasing. Limited data exists on complications associated with IUD. However, to date there is no data available on the risk of adhesion formation and associated morbidities, if a perforation occurs with metal containing versus levonorgestrel releasing IUD. The primary purpose of this systematic review was to compare the potential for adhesion formation between metal containing and levonorgestrel releasing IUD.

METHODS:

A PubMed electronic search with key words and subject heading “intrauterine device” and “perforation” was performed. Patient demographics, class of IUD, site of adhesion formation and the description of these adhesions were tabulated. The adhesions were classified into 3 groups: Group I, II and III based on the degree of the adhesions (dense/severe to filmy). The degree of intra-peritoneal adhesion formation and the class of IUD was analyzed.

RESULTS:

Seventy five articles describing 85 cases were included in the study. Metal containing devices were found to have a statistically higher number of dense adhesions compared to levonorgestrel releasing IUD (P=.000056). The sigmoid colon (22%) was found to be the most common site of adhesions formation following perforation of IUD. Laparotomy was performed in 59% of cases in which a metal containing IUD had perforated.

CONCLUSION:

The degree of intra peritoneal adhesions following IUD perforation depends on whether the IUD is metal containing. Further studies are warranted to establish the significance of this in patient selection criteria.
Novel Use of Viable Cryopreserved Umbilical Tissue in Posterior Colporrhaphy in High Risk Patients [16J]
Authors: Karon Magdalene , Trimpe Darcy M.
Published: May 2019

INTRODUCTION:

Rectocele is a common finding in parous women. While mild to moderate cases are asymptomatic, once a rectocele becomes symptomatic it carries a high risk of recurrence following surgical correction. The prolonged and inefficient healing in this region may be due to the constant bacterial exposure and pressure from straining. This risk is increased in patients who are smokers, diabetic, or immune compromised. An ideal adjunct would promote endogenous regeneration of the tissue defect, minimize inflammatory scar tissue formation, have antimicrobial factors, growth factors, and improve neovascularization. We present a novel use of viable cryopreserved umbilical tissue (vCUT) in posterior colporrhaphy. vCUT is a human tissue allograft regulated by the FDA under 21 CFR part 1271 part 361 human cells, tissue and cellular/tissue based products. It can be utilized for acute and chronic wounds of various etiologies at any location in the body.

METHODS:

Ten patients were followed for up to a year following posterior colporrhaphy with vCUT incorporated into the closure.

RESULTS:

Our data showed patient satisfaction with healing. Patient satisfaction included post-operative complaints, such as pain, discharge, and symptomatic relief of rectocele symptoms. Physical examination showed minimal symptomatic granulation tissue that caused bleeding or discharge. There were no break downs of sutures or infection complications requiring antibiotics.

CONCLUSION:

vCUT is a commercially available product that shows promise in improving rectocele healing. Our small study showed no recurrence for up to a year post surgery and no complications to date have been reported that are attributed to the use of vCUT.
Predictors of Chronic Opioid Use Among Women With Endometriosis [18J]
Authors: Chiuve Stephanie E. , Kilpatrick Ryan D. , Petruski-Ivleva Natalia , Wegrzyn Lani R. , Snabes Michael C. , Bateman Brian T.
Published: May 2019

INTRODUCTION:

Women with endometriosis are prescribed opioids for pain relief but may have other risk factors for chronic opioid use. The identification of predictors of chronic use in this population may provide clinical guidance for treatment selection.

METHODS:

Women with an initial claim for endometriosis (N=39,513) aged 18-50 years were identified from a US commercial insurance claims database and followed for 2 years. Chronic opioid use was defined as ≥10 fills or ≥120 days covered in 365 days. Multivariable logistic regression models were used to identify potential predictors of chronic opioid use.

RESULTS:

Over 2 years, 4.4% of women with endometriosis became chronic opioid users. Risk factors for chronic use included fibromyalgia (OR 1.54; 95% CI 1.12-2.10), back pain (OR 1.42; 95% CI 1.15-1.75), migraines (OR 1.39; 95% CI 1.07-1.81), tobacco use (OR 1.56; 95% CI 1.22-2.00), antidepressants (OR 1.69; 95% CI 1.39-2.05), antipsychotics (OR 2.03; 95% CI 1.41-2.91), benzodiazepine (OR 1.57; 95% CI 1.27-1.94) and prior use of opioids (OR 4.83; 95% CI 4.02-5.81). These characteristics were more frequent in women with than without endometriosis: fibromyalgia (4% vs 2%), back pain (14% vs 8%), migraines (6% vs 2%), tobacco use (4% vs 2%), antidepressants (19% vs 13%), antipsychotics (2% vs 1%), benzodiazepine (11% vs 5%) and prior use of opioids (34% vs 13%) (p<0.01).

CONCLUSION:

Women with endometriosis who are exposed to opioids and are at high-risk for chronic opioid use may be identified based on comorbidities and concomitant medication use. Opioid prescribing should be carefully considered among high-risk women.
Effects of TX-001HR in Women With Menopause [19J]
Authors: Kagan Risa , Constantine Ginger , Graham Shelli , Bernick Brian , Mirkin Sebastian
Published: May 2019

INTRODUCTION:

In the REPLENISH trial, women with ≥50 moderate to severe hot flushes (HF)/week (VMS substudy [efficacy population; consistent with FDA guidance]) treated with TX-001HR (17β-estradiol [E2]/progesterone [P4]) had significant improvements in HF frequency and severity compared with placebo at weeks 4 and 12. This post hoc analysis evaluated HFs with TX-001HR in women with <50 moderate to severe HF/week.

METHODS:

REPLENISH (NCT01942668) was a phase 3, randomized-controlled trial of postmenopausal women (40–65 years; intact uterus). Women not in the VMS substudy (with <50 moderate to severe HF/week) were randomized 1:1:1:1 to daily E2/P4 (mg/mg) of 1/100 (n=275), 0.5/100 (n=273), 0.5/50 (n=274), 0.25/50 (n=269). Changes and percent changes from baseline in frequency and severity of HF at weeks 4 and 12 were determined.

RESULTS:

The mean number was 24.4–27.6 HF/week and mean severity score was 2.28–2.36 (ie, moderate to severe) at baseline. Women treated with E2/P4 doses had improvements from baseline in frequency of 11.8–16.2 HFs at week 4 and 16.6–19.5 HFs at week 12, corresponding to percent changes of 48%–66% and 67%–80%, respectively. Improvements from baseline in severity were 0.64–0.88 points at week 4 and 0.97–1.37 points at week 12, corresponding to percent changes of 28%–38% and 43%–60%, respectively.

CONCLUSION:

The magnitude of improvements in frequency and severity observed with TX-001HR in women with <50 HF/week was similar to the significant improvements observed in women with ≥50 HF/week for frequency (67%–75%) and severity (30%–44%) at week 12. The benefits of TX-001HR may extend to women who have less frequent HF.
Sustained Improvements in Anemia and Fatigue of AUB after a Single Course of Ferumoxytol: 6-Month Follow-up [20J]
Authors: Dahl Naomi V. , Moore Anne , Jiang John , Strauss William E.
Published: May 2019

INTRODUCTION:

Iron deficiency anemia (IDA) associated with abnormal uterine bleeding (AUB) negatively impacts patients' health-related quality of life (HRQOL). A Phase 3 double-blind, placebo-controlled trial (NCT01114139) previously found that patients unsuccessfully treated with oral iron had very poor baseline HRQOL scores associated with fatigue, and that IV iron treatment resulted in significant, clinically meaningful improvement. This subgroup analysis reports the impact of a single course of IV iron in women with AUB during the following 6-month extension study (NCT01114217).

METHODS:

Patients with persistent or recurrent IDA (Hgb <11.0 g/dL and TSAT <20%) at any time during the extension study received ferumoxytol (2x510 mg IV, 3 to 8 days apart). Functional Assessment of Chronic Illness Therapy-Fatigue Scale (FACIT-Fatigue), and Linear Analogue Scale Assessment (LASA) -Energy, -Activities of Daily Living (ADL) and -HRQOL were administered at each monthly visit. The study was IRB-approved.

RESULTS:

Most patients in the extension study did not require further doses, including 56% (119/212) of those with AUB. At Baseline of the double-blind trial (Hgb 9.0±0.9 g/dL) their FACIT-Fatigue scores were lower (23.6±11.85) than general (non-anemic) US population norms (40.1-43.6), and comparable to scores of anemic cancer patients receiving chemotherapy (23.9). By Week 5 FACIT-Fatigue increased significantly (37.4±10.84), and was sustained over 6 months (Month 7 score 40.7±11.53, Hgb 11.9±1.23). Significant improvements in all the LASA domains were also maintained.

CONCLUSION:

This study found that for the majority of patients, significant improvements in fatigue and quality of life domains were achieved and sustained for 6 months following a single treatment of ferumoxytol.
Brexanolone Injection Administration to Lactating Women: Breast Milk Allopregnanolone Levels [30J]
Authors: Hoffmann Ethan , Wald Jeffrey , Dray Danielle , Colquhoun Helen
Published: May 2019

INTRODUCTION:

Brexanolone injection (BRX), an investigational, intravenous formulation of the GABAA receptor positive allosteric modulator allopregnanolone is in development for postpartum depression (PPD) pharmacotherapy. Allopregnanolone levels were evaluated in breast milk and plasma from healthy lactating women administered BRX.

METHODS:

IRB approval was obtained. Informed consent was required for enrollment. Subjects (n=12) received a 60-hour inpatient BRX infusion (titration to 90 µg/kg/h followed by a taper phase) and were followed through Day 7 as outpatients. Breast milk and plasma allopregnanolone were quantified using liquid chromatography-mass spectrometry (limits of quantitation: milk = 5 ng/mL, plasma = 1 ng/mL). Subjects pumped breast milk as needed. All breast milk was collected. PopPK model structures were considered to account for milk sample frequency and the lack of strict alignment between pumping and plasma collection. The most parsimonious model was used to describe milk concentrations as the product of a constant partition coefficient and plasma allopregnanolone concentration. Modeling accounted for milk and plasma values below the limit of quantitation.

RESULTS:

The model characterized milk and plasma data well; allopregnanolone concentrations increased during titration and declined during taper for plasma and milk, in parallel. Milk concentrations were 1.36 times higher than plasma. Modeling predicts that 95% of patients with 90 µg/kg/h dosing will have milk allopregnanolone levels <10 ng/mL 36 hours after treatment cessation. The calculated relative infant dose (RID) was 1.3%.

CONCLUSION:

Following BRX dosing, PopPK modeling characterized allopregnanolone concentrations in milk and plasma and suggests that the RID for BRX is associated with low risk to breastfed infants.
Clinical Experience for Noninvasive Prenatal Screen in Assisted Reproductive Technology Pregnancies [34J]
Authors: Hancock Susan , Ben-Shachar Rotem , Adusei Christa , Haverty Carrie , Goldberg Jim
Published: May 2019

INTRODUCTION:

Describe clinical performance of a whole genome sequencing-based noninvasive prenatal screen (NIPS) in pregnancies achieved via assisted reproductive technology (ART).

METHODS:

After securing IRB-exempt status, we retrospectively analyzed results from 58,105 patients who underwent NIPS during a nine-month period to assess clinical performance of Trisomy 21, 18, and 13 in singleton pregnancies. Four percent (2,435 pregnancies) reported being conceived via ART. Fetal fraction (FF) was measured for all patients but was not used as a stand-alone reason for test failure. We sought pregnancy outcomes for all patients who screened positive and for 10% of those who screened negative. Voluntarily reported outcomes were also accepted. Concordance of results was determined with respect to pregnancy outcome. Clinical sensitivities and specificities were calculated, adjusting cohort size for ascertainment bias.

RESULTS:

The total patient cohort included average-risk (43%, n=24,751) and high-risk patients (57%, n=33,354). For the ART population, median maternal age was 36 years and median gestational age was 12.0 weeks. The screen yielded a result for 99.7% of ART patients; no result was issued for the remaining 0.3% of samples (n=7). Screen positive rate was 0.7%. Informative outcomes were received for 50% of positive results in the ART cohort; nine true positives and one false positive. Observed sensitivities for Trisomy 21 and Trisomy 18 were 100% and 100%, respectively, in ART pregnancies. No patients screened positive for Trisomy 13. No false negatives were reported.

CONCLUSION:

Results demonstrate that NIPS in our laboratory achieves high accuracy while maintaining a low test-failure rate in pregnancies conceived via ART.
Effect of Smoking History on Inpatient Postpartum Opioid Use [2K]
Authors: Blitz Matthew J. , Prasannan Lakha , Greenberg Meir , Marchbein Harvey , Rochelson Burton L.
Published: May 2019

INTRODUCTION:

To determine if inpatient postpartum opioid utilization is affected by smoking history.

METHODS:

Retrospective cohort of singleton deliveries at ≥37 weeks of gestation in which smoking status was documented on admission at a tertiary hospital from 2013-2016. Patients were excluded for NSAID or opioid allergies, drug abuse history, positive urine toxicology, general anesthesia for delivery, and incomplete records. Outcomes evaluated were mode of delivery, medications administered for postpartum analgesia, and total doses received.

RESULTS:

A total of 17,280 pregnancies were included: 83 current, 890 former and 16,307 non-smokers. The cesarean delivery rate was higher among current or former smokers compared to non-smokers (45.9% vs. 34.3%, P<0.0001). After cesarean delivery, current or former smokers were more likely to receive oxycodone (82.3% vs. 75.8%, P<0.002), to have it administered at higher total amounts (98 vs. 84 grams, P<0.001), and to exceed the 90th percentile for consumption (12.5% vs. 8.3%, P<0.009). After vaginal delivery, current or former smokers were also more likely to receive oxycodone (41.8% vs. 31.3%, P<0.0001), to have it administered at higher total amounts (54 vs. 42 grams, P<0.0001), and to exceed the 90th percentile for consumption (15.9% vs. 9.2%, P<0.003). There was no difference in the rate of additional breakthrough opioid medications based on smoking history.

CONCLUSION:

Women who are current or former smokers are more likely to receive oxycodone for postpartum analgesia compared to non-smokers, and at increased amounts. A precision medicine approach using personalized treatment algorithms may improve pain management in this population.
Effects of Methadone and Buprenorphine Use During Pregnancy on Neonatal and Maternal Outcomes [4K]
Authors: Moustafa Ahmed S. Z. , Kumar Navin , Masten Megan , Bruder Adrienne , Rocha Frederico , Adekola Henry
Published: May 2019

INTRODUCTION:

The opioid epidemic in continues to be a major public health concern. Opioid use during pregnancy increases risks of adverse neonatal and maternal outcomes, including neonatal abstinence syndrome (NAS). Methadone and Buprenorphine are used as maintenance therapy for opioid dependence during pregnancy. Our objective is to compare effects of Methadone and Buprenorphine on maternal and neonatal outcomes.

METHODS:

This is a retrospective cohort study that included patients with a singleton pregnancy who received opioid maintenance therapy and delivered at Hurley Medical Center from 2012 - 2017. IRB approval was obtained. Primary outcome was length of neonatal stay. Demographic characteristics, illicit drug use, and tobacco smoking were among variables analyzed in the Methadone and Buprenorphine groups.

RESULTS:

The study included 228 participants. 47 were on Buprenorphine and 181 on Methadone. Of the neonates, 71% required treatment for NAS. The median length of treatment in days was significantly less in Buprenorphine group (p= 0.001; 10 vs 16), along with median length of stay (p= 0.000001; 12 vs 20). There was no association between Buprenorphine dose and NAS treatment. In the Methadone group, the median dose increased with the level of treatment (p=0.004). After correcting for potential confounders, we noted that gestational age, dose of methadone, and illicit drug use, were associated with higher risk of requiring NAS treatment.

CONCLUSION:

Neonates exposed to Buprenorphine had significantly lower rates of NAS and shorter NICU stay compared to Methadone. Gestational age at delivery, Methadone dose, and illicit drug use seem to be associated with increased NAS treatment.
Establishing a Lower Cutoff Value for Early Gestational Diabetes Screening [6K]
Authors: Loehr Frederick W. , Mackeen Awathif D. , Paglia Michael J. , Nordberg Cara
Published: May 2019

INTRODUCTION:

Women who are not diagnosed with gestational diabetes mellitus (GDM) on early screening prior to 20 weeks go on to complete routine screening at 24-28 weeks. The aim of this study was to establish a low cutoff value for the early one-hour, 50-g glucose test (Glucola) under which no subsequent testing would be necessary.

METHODS:

This was an IRB-approved retrospective cohort study whereby electronic medical records in the Geisinger system between 1/1/2010 and 12/31/2016 were searched for all women who had an early Glucola and completed all subsequent indicated testing for GDM. For women with a result on the early Glucola less than 130 mg/dL, the risk of developing GDM for a given value was examined to identify a level below which further testing for GDM in the pregnancy may not be necessary. The primary outcome was percentage of women diagnosed with GDM at any point in the pregnancy for a given result on the early Glucola.

RESULTS:

There were 3040 women identified as having completed an early Glucola and 2405 women had a result less than 130 mg/dL. 174 of these women were subsequently diagnosed with GDM at some point in the pregnancy. The negative predictive value (NPV) for not developing GDM was greater than 90% for any one-hour glucose result less than 130 mg/dl. A result less than 114 mg/dL was shown to have a 95% NPV for not developing GDM.

CONCLUSION:

Forgoing routine screening in women with an early one-hour Glucola result below 114 mg/dL may be a viable option.
Healthcare Resource Utilization and Costs Among Young Children of Women With Postpartum Depression (PPD) [4O]
Authors: Huang Ming-Yi , Packnett Elizabeth , Zimmerman Nicole M. , Moynihan Meghan , Eldar-Lissai Adi , Simas Tiffany Moore
Published: May 2019

INTRODUCTION:

A retrospective cohort analysis was conducted using claims-based data from IBM MarketScan® Research Databases to assess healthcare resource utilization and costs (HRUC) in children of mothers with presence or absence of postpartum depression (PPD).

METHODS:

Women with live births from January 1, 2010 to September 30, 2015 (index date=delivery date) were identified and linked to their newborns. The mother-child pairs were divided into PPD and non-PPD cohorts based on medical and pharmacy claims for depression, mood or adjustment disorders, or anxiety identified in the mother between 15 to 365 days after delivery. Children were required to have 24 months of continuous enrollment following delivery. Propensity score matching (1:3) was used to adjust for underlying differences in the PPD and non-PPD cohorts.

RESULTS:

135,678 matched mother-child pairs (PPD: 33,314; non-PPD: 102,364), were analyzed. In the first 24 months of life, children of mothers with PPD had significantly higher healthcare resource utilization across most service categories compared to those without PPD. Among outpatient services, the percentage of children with a physician specialist service, early-intervention screening, and an emergency room visit were 3-7% greater in children of mothers with PPD (p<0.001). In the first 24 months of life, children of mothers with PPD incurred a 12% higher total healthcare costs compared to children of mothers without PPD ($24,572 versus $21,946; p<0.001).

CONCLUSION:

In children of mothers with claims-based evidence of PPD in the first postpartum year, healthcare resource utilization and costs in the first 24 months of life exceeded that of children of mothers without evidence of PPD.
Is the Shirodkar a Better Technique for Ultrasound Indicated Cerclages? [9O]
Authors: McColm Jordan , Lindsay Kathryn , Brooks Jennifer , Hwang Joseph , Ta-Chung Lee Gene
Published: May 2019

INTRODUCTION:

Studies comparing the Shirodkar vs McDonald technique for an ultrasound indicated cerclage are limited, but suggest improved outcomes with Shirodkar. We sought to compare our real-world experiences using either technique with reported outcomes from clinical trials. We specifically compared these 2 techniques in the context of a ultrasound indicated cerclage for short cervix.

METHODS:

A retrospective study at 2 hospitals was conducted. IRB approval was obtained. A query for patients with a short cervix (<25 mm) diagnosed by TVUS before 24w0d was conducted. (KUMC between 1/1/2008 - 6/1/2016, and VMC-UW Medicine between 1/2016 - 5/2018). Patients who underwent an ultrasound-indicated cerclage were then analyzed and grouped by surgical technique. Primary outcome was length of time from cerclage until delivery (days). Data was analyzed by T-tests.

RESULTS:

A total of 51 patients were analyzed. There were demographic and clinical differences between the groups. The Shirodkar group was white and Asian, and did not include Hispanic or African American ethnicity. The gestational age at diagnosis was later (154 vs 139 days), and the TVCL was longer (11.4 vs 7.7 mm). The Shirodkar group had better outcomes. The length of time from cerclage until delivery was longer (109 vs 90 days), the gestational age at delivery was older (263 vs 228 days), and the newborn birthweight was larger (2990 vs 2155 gm).

CONCLUSION:

The Shirodkar group had better outcomes, but they also appeared to be a fundamentally lower risk pregnancy. The benefit of Shirodkar technique remains unclear. Analysis by multiple regression is pending.
Patient Perceptions of Medications That Reduce the Risk of Preterm Delivery and Preeclampsia [12O]
Authors: Bradley Danielle , Cobb Christina , Landau Erin , Wolfberg Adam
Published: May 2019

INTRODUCTION:

The objective of this study was to understand patient perceptions of the safety and efficacy of medications (progesterone and low-dose aspirin) for the purpose of avoiding a preterm delivery and preeclampsia.

METHODS:

A survey about perceptions of progesterone and a survey about low-dose aspirin use and safety during pregnancy were sent to users of a pregnancy mobile app. Respondents were age 18 or older and pregnant.

RESULTS:

Among respondents who were not prescribed progesterone (n=4,421), but indicated a history of preterm delivery (n=115, 3%) or a short cervix (n=20, 0.05%), barriers cited for obtaining a progesterone prescription were disbelief in the efficacy of the medication, concerns about cost, and discomfort discussing with their provider. Prior to reading information about progesterone efficacy, 35% agreed that progesterone can help prevent preterm delivery, compared to 60% agreement after reading the information. The results of the low-dose aspirin survey showed that 200 women (19%) agreed that taking low-dose aspirin during pregnancy was safe, while 435 women (43%) had concerns about taking it during pregnancy. When asked the extent to which they agreed that taking low-dose aspirin during pregnancy can reduce the risk of delivering preterm and developing preeclampsia, 10% and 13% agreed, respectively. Nearly half (48%) reported that they would take a medication recommended by their provider without hesitation.

CONCLUSION:

Patients are skeptical of the efficacy and safety of low-dose aspirin and progesterone during pregnancy. Results indicate that more can be done to educate patients about medications that have demonstrably shown to reduce risk of obstetric complications.
PLGF Predicts Latency to Delivery for Patients Undergoing Evaluation for Hypertension [14O]
Authors: Martinez-King Lorena Carolina , Adami Rebecca Recker , Roeder Hilary Alpert , Ballas Jerasimos , Woelkers Douglas Andrew , Laurent Louise
Published: May 2019

INTRODUCTION:

Preeclampsia (PE) is a pregnancy-specific syndrome of vascular dysfunction characterized by hypertension and end-organ injury. The traditional evaluation of PE requires time-consuming assessment of nonspecific findings which can lead to prolonged, and possibly unnecessary, hospitalization. Placental growth factor (PLGF) has shown promise as a novel biomarker for PE. We hypothesize that levels of PLGF will correlate with latency to delivery and that PLGF levels will differ between women who received a short (0-8 hours) triage evaluation and those who received a long (>8 hours) evaluation or were admitted to the hospital.

METHODS:

Women undergoing evaluation for signs or symptoms of PE at UCSD OB Triage who were between 20 0/7-37 0/7 weeks gestation were prospectively recruited. Maternal plasma was collected at the time of evaluation and stored. PLGF was quantified using an ELISA assay (Alere). The pregnancy outcome diagnosis for each subject was adjudicated.

RESULTS:

132 study subjects undergoing evaluation for hypertension at UCSD between 8/2015 and 3/2018 were enrolled. Subjects with a positive PLGF were significantly more likely to have a 1 week latency to delivery (77.0% vs 37.5%; p<0.01), yielding an odds ratio of 3.2 (1.2 - 8.5); p<0.05).

CONCLUSION:

When evaluating a patient for preeclampsia, the presence of PLGF in the maternal plasma is reassuring and indicative of at least a 1 week latency to delivery. The use of PLGF to aid in decision-making may lead to decreased time spent during triage evaluation, decreased days of hospitalization, and optimal use of antenatal steroids in patients presenting for evaluation for preeclampsia.
The Effect of Prophylactic Intravascular Balloon Catheterization on Surgical Outcomes in Morbid Adherent Placenta [18O]
Authors: Abdelrahman Hisham , Babarinsa Isaac , Raughley Moune Jabre
Published: May 2019

INTRODUCTION:

The target was to determine the effect of using internal iliac artery balloon catheterization (IIABC) in morbidly adherent placenta previa on surgical outcomes during cesarean section.

METHODS:

A retrospective comparative study was conducted from January 2013 till Oct 2016. From 67 women with morbidly adherent placenta during this time period- 33 underwent IIBAC before cesarean section (study group) and 34 underwent cesarean section without (control group). The outcomes measured were intra-operative blood loss, units of blood transfusion, loss in hemoglobin and hematocrit, total operative time, hemostatic medications and surgical procedures used, and the duration of hospital stay.

RESULTS:

The demographics were comparable, with no difference in maternal age (P=1), nationality (P=.86), BMI (P=.8), parity (P=.26), gestation (P=.31), pre-op hemoglobin (P=.736) and maternal co-morbidities like anemia (P=.7), diabetes (P=.5) and hypertension (P=.08). No significant difference was noted in the mean intra-operative blood loss (3115±1745 vs. 3447±2352, P=.515), transfusion ≥-6 units (30.3% vs. 41.17%, P=.357), duration of hospital stay (6.18±3.32 vs. 5.61±3.48, P=.495), loss in hemoglobin (2.158±1.758 vs. 1.68±1.69, P=.26) and the use of medications and surgical procedures. The use of general anesthesia was more in the study group (P=.049), with no difference in the neonatal factors.

CONCLUSION:

The use of IIABC as a means to reduce the intra-operative maternal morbidity is questionable, since the evidence proving the benefit is limited. In this case series, there were no statistical difference in the hemorrhagic outcome between women in whom it was used.
Uterine Bioelectrical Activity in Pregnant Women With a Short Cervix in the Mid-Trimester [19O]
Authors: Marinescu Ponnila S. , Miller Lauren Anne , Young Roger C. , Hern Braxton , Pressman Eva K. , Seligman Neil Stuart
Published: May 2019

INTRODUCTION:

Mechanisms of mid-trimester cervical shortening (<2.5cm) are unclear, and it is unknown if subclinical uterine activity plays a causative role. The purpose of this study is to characterize uterine bioelectrical activity by uEMG in women with a short cervix in the mid-trimester.

METHODS:

This is an observational cohort study of pregnant women at an urban academic medical center from November 2017 to June 2018. Women with short cervical length (CL) <2.5 cm were compared to women with normal CL (≥3 cm). Primary outcome was pattern of bioelectrical activity in both groups. Secondary outcomes were characteristics of identified signals. All subjects had a singleton pregnancy between 16w0d and 22w6d. Up to 4 proprietary uEMG electrode pads (PreTel, Inc., Chattanooga, TN), 4 commercially available ECG pads, a ground electrode, and a tocometer were placed on the lower abdomen. EMG recordings were obtained for 60 minutes using a Porti amplifier (TMSi, Oldenzaal, Netherlands) and analyzed between 0.15 and 1.2 Hz.

RESULTS:

Seven subjects were included, 4 with short CL and 3 with normal CL. Isolated spike and burst signals were identified during recordings. Spikes were observed in both groups, but burst-type signals were observed only in the short CL group. In women with short CL, 3 bursts in 4 subject hours of monitoring were appreciated.

CONCLUSION:

Burst-type signals in women with a short CL, while infrequent, are a novel finding. Our results need to be replicated in larger studies requiring prolonged subject monitoring (e.g., 10hr/patient). This would necessitate using wearable electrodes to allow for uninterrupted recording during daily activity.
Validation of Noninvasive Prenatal Testing for Fetal Aneuploidies and Microdeletions Down to 2% Fetal Fraction [20O]
Authors: Mito Yoshiko , McCafferty Jonathan , Calder Robert , Lu Xingwu , Gross Susan , Edelmann Lisa
Published: May 2019

INTRODUCTION:

Noninvasive prenatal testing (NIPT) by massively parallel sequencing of cell-free DNA in maternal plasma detects fetal aneuploidies with high sensitivity and specificity. However, accurate detection of fetal aneuploidies in samples with low fetal fraction remains challenging.

METHODS:

We have developed an NIPT pipeline that utilizes a statistical model-based counting algorithm to (1) calculate the representation of genomic regions of interest; (2) estimate the fetal fraction; (3) assess the fetal sex by Y chromosome representation; (4) determine the risk of fetal aneuploidies and microdeletions. The training set was modeled using 2,813 euploid samples (1,673 male and 1,140 female fetuses). For intermediate result calls, assessment incorporated likelihood ratios. Sensitivities and specificities were dynamically calculated in relation to both sequencing read depth and fetal fraction to set reporting thresholds.

RESULTS:

This clinical pipeline tested with 2,253 samples including 98 known positive samples for aneuploidies of chromosomes 21, 18, 13, 16, 22, 15, X and Y as well as microdeletions of subchromosomal regions (22q11.2, 1p36, 15q11.2-q13, 4p16, 5p15, 11q23, and 8q24). Results were called with both sensitivity and specificity >99% for common aneuploidies. The observed normalized chromosome values closely fit the statistical model's estimation, indicating accurate aneuploidy calls down to 2% fetal fraction.

CONCLUSION:

In this study, we present a validation model for an NIPT pipeline utilizing a statistical model-based counting algorithm that can accurately detect the fetal aneuploidies and microdeletions down to low fetal fraction.
Opportunity for Cancer Prevention: 1 in 4 Unaffected Women Meet Hereditary Cancer Testing Criteria [26O]
Authors: Bucheit Leslie , Ready Kaylene , Brown Jonathan , Goldberg James D.
Published: May 2019

INTRODUCTION:

Estimates show 5-10% of cancer is hereditary. OB/GYNs play an important part in identifying hereditary cancer syndromes (HCS) for women unaffected with cancer; however, the prevalence of HCS in this population is not well studied. This study describes the prevalence of HCS among unaffected female patients as measured by meeting National Comprehensive Cancer Network (NCCN) criteria for genetic testing for BRCA-related, Lynch, and/or polyposis syndromes.

METHODS:

A personalized link was sent to patients prior to their annual OB/GYN visit requesting that they report personal and family cancer history (PFHx) to a digital tool that aligns PFHx to NCCN genetic testing criteria for HCS. Responses were collected between 2/1/18 and 9/1/18; data were then de-identified and analyzed.

RESULTS:

Of 4226 possible patients, 2334 entered PFHx into the digital tool, 94% (n=2199) of whom were unaffected. 23% (n=506) of unaffected patients met NCCN criteria for HCS genetic testing including 82% for BRCA, 15% for Lynch syndrome, and 3% for polyposis syndromes; 6.5% met criteria for multiple syndromes. An additional 1.3% met criteria due to a reported familial mutation. Unaffected patients who reported PFHx averaged 42 years of age (range: 18 to 83) and 93% reported Caucasian (60%), Asian (16%), African-American (10%), or Ashkenazi Jewish (7%) ethnicity.

CONCLUSION:

Nearly 1 in 4 unaffected patients presenting for annual OB/GYN visits met NCCN genetic testing criteria for HCS. Many patients may benefit from OB/GYNs employing standardized ways to identify HCS.
Medroxyprogesterone Eliminates Abnormal Bleeding With a Levonorgestrel Intrauterine System (LNG-IUS) [4P]
Authors: Benor Ariel , Kulak David , Naroji Swetha Jaya
Published: May 2019

INTRODUCTION:

Abnormal vaginal bleeding is a common side effect seen in the majority of patients in the first six months after LNG-IUS placement. Some women may desire its removal because of this effect. The objective of this study was to assess the ability of medroxyprogesterone (MP) to reduce this initial bleeding transition period.

METHODS:

We prescribed a tapering regimen of medroxyprogesterone (MP) overlapping the first 35 days with the LNG-IUS. Four women who desired amenorrhea adhered to this regimen: on day three of their menses, they began a 14-day course of MP 10 mg daily; on day four, the LNG-IUS was inserted; on day 17, the MP was reduced to 5 mg daily for ten days; on day 27, the MP was reduced to 2.5 mg daily for ten days. The women were given a diary to record their bleeding pattern.

RESULTS:

All four women (100%) became amenorrheic within seven days of LNG-IUS insertion and remained so for the duration of use with the LNG-IUS (>1 year). Three out of four (75%) recorded 3-5 days of spotting for the first 1-4 months with the LNG-IUS.

CONCLUSION:

Our tapering regimen of MP overlapping the first 35 days with an LNG-IUS is sufficient to eliminate the initial period of abnormal bleeding. Iatrogenic amenorrhea may alleviate many patients' feelings of anxiety as well as other menstrual symptoms, and this may affect a patient's decision to continue using the LNG-IUS. More research is required to validate this study.
Patterns of and Attitudes Towards Cannabis Use in Women's Health [7P]
Authors: Alton Katie , Han Leo , McCrimmon Sara , Darney Blair , Colwill Alyssa Covelli , Jensen Jeffrey T.
Published: May 2019

INTRODUCTION:

Legal access to cannabis is increasing and its use to treat medical conditions has been shown to be effective and common. We sought to assess the use of and attitudes towards cannabis for treating gynecological conditions.

METHODS:

We utilized Amazon.com Inc.'s Mechanic Turk platform to administer a 21-question survey of US women. We present descriptive results of socio-demographic information, cannabis use for recreational and medicinal purposes, and attitudes about cannabis use for gynecologic conditions. We used bivariate statistics to test associations between past cannabis use and attitudes towards use for gynecologic conditions.

RESULTS:

We obtained responses from 1011 women from all 50 states. Respondents primarily identified as white (83%), with a median age of 37 (range 19-82). Sixty-four percent reported they had ever used a cannabis product. Among respondents who had used cannabis (n=648), 36% (n=232) reported using it to treat a specific medical condition; pain and depression/anxiety were the most common conditions. Of these women, 16% (38/232) reported cannabis use to treat a gynecologic condition; menstrual cramps was the most common condition. Of respondents reporting ever using cannabis, 49% (490/1011) stated they would consider using cannabis to treat pain associated with medical abortion, 47% (n=480/1011) would use for surgical abortion pain, and 48% would use for pain with IUD insertion (n=489/1011). Among respondents who have never used cannabis, 63% (n=229/362) would considering using cannabis to treat a gynecologic condition.

CONCLUSION:

Cannabis products are currently being used by women both recreationally and medically. Most women would consider using cannabis to treat gynecologic conditions.