CYP2D6 Activity Is Correlated with Changes in Plasma Concentrations of Taurocholic Acid during Pregnancy and Postpartum in CYP2D6 Extensive Metabolizers.

Cytochrome P450 2D6 (CYP2D6) is involved in the metabolism of >20% of marketed drugs. CYP2D6 expression and activity exhibit high interindividual variability and is induced during pregnancy. The farnesoid X receptor (FXR) is a transcriptional regulator of CYP2D6 that is activated by bile acids. In pregnancy, elevated plasma bile acid concentrations are associated with maternal and fetal risks. However, modest changes in bile acid concentrations may occur during healthy pregnancy, thereby altering FXR signaling. A previous study demonstrated that hepatic tissue concentrations of bile acids positively correlated with the hepatic mRNA expression of CYP2D6. This study sought to characterize the plasma bile acid metabolome in healthy women (n = 47) during midpregnancy (25-28 weeks gestation) and ≥3 months postpartum and to determine if plasma bile acids correlate with CYP2D6 activity. It is hypothesized that during pregnancy, plasma bile acids would favor less hydrophobic bile acids (cholic acid vs. chenodeoxycholic acid) and that plasma concentrations of cholic acid and its conjugates would positively correlate with the urinary ratio of dextrorphan/dextromethorphan. At 25-28 weeks gestation, taurine-conjugated bile acids comprised 23% of the quantified serum bile acids compared with 7% ≥3 months postpartum. Taurocholic acid positively associated with the urinary ratio of dextrorphan/dextromethorphan, a biomarker of CYP2D6 activity. Collectively, these results confirm that the bile acid plasma metabolome differs between pregnancy and postpartum and provide evidence that taurocholic acid may impact CYP2D6 activity during pregnancy. SIGNIFICANCE STATEMENT: Bile acid homeostasis is altered in pregnancy, and plasma concentrations of taurocholic acid positively correlate with CYP2D6 activity. Differences between plasma and/or tissue concentrations of farnesoid X receptor ligands such as bile acids may contribute to the high interindividual variability in CYP2D6 expression and activity.

Pregnancy Has No Clinically Significant Effect on the Pharmacokinetics of Bupropion or Its Metabolites.

BACKGROUND: Bupropion (BUP) is a chiral antidepressant and smoking cessation aide with benefits and side effects correlated with parent and active metabolite concentrations. BUP is metabolized by CYP2B6, CYP2C19, and CYP3A4 to hydroxy-BUP (OH-BUP) as well as by 11ß-hydroxysteroid dehydrogenase-1 and aldo-keto reductases to threohydrobupropion (Threo) and erythrohydrobupropion (Erythro), respectively. As pregnancy alters the activity of drug-metabolizing enzymes, the authors hypothesized that BUP metabolism and BUP metabolite concentrations would be altered during pregnancy, potentially affecting the efficacy and safety of BUP in pregnant women. METHODS: Pregnant women (n = 8) taking BUP chronically were enrolled, and steady-state plasma samples and dosing interval urine samples were collected during pregnancy and postpartum. Maternal and umbilical cord venous blood samples were collected at delivery from 3 subjects, and cord blood/maternal plasma concentration ratios were calculated. The concentrations of BUP stereoisomers and their metabolites were measured. Paired t tests were used to compare pharmacokinetic parameters during pregnancy and postpartum. RESULTS: No significant changes were observed in the steady-state plasma concentrations, metabolite to parent ratios, formation clearances, or renal clearance of any of the compounds during pregnancy when compared with postpartum. The umbilical cord venous plasma concentrations of BUP and its metabolites were 30%-60% lower than maternal plasma concentrations. CONCLUSIONS: This study showed that there are no clinically meaningful differences in the stereoselective disposition of BUP or its metabolites during pregnancy, indicating that dose adjustment during pregnancy may not be necessary. The results also showed that the placenta provides a partial barrier for bupropion and its metabolite distribution to the fetus, with possible placental efflux transport of bupropion and its metabolites.

Chronic Liver Disease in the Obstetric Patient.

Chronic liver disease in pregnancy is rare. Historically, many chronic liver diseases were considered contraindications to pregnancy; however, with current monitoring and treatment strategies, pregnancy may be considered in many cases. Preconception and initial antepartum consultation should focus on disease activity, medication safety, risks of pregnancy, as well as the need for additional monitoring during pregnancy. In most cases, a multidisciplinary approach is necessary to ensure optimal maternal and fetal outcomes. Despite improving outcomes, pregnancy in women with the chronic liver disease remains high risk.

An enhanced recovery after surgery pathway for cesarean delivery decreases hospital stay and cost.

BACKGROUND: Enhanced recovery after surgery pathways provide a multidisciplinary, evidence-based approach to the care of surgical patients. They have been shown to decrease postoperative length of stay and cost in several surgical subspecialties, including gynecology, but have not been well-studied in obstetric patients who undergo cesarean delivery. OBJECTIVE: We sought to determine whether the implementation of an enhanced recovery after surgery pathway for cesarean delivery would decrease postoperative length of stay and postoperative direct cost compared with historic controls. STUDY DESIGN: We conducted a retrospective cohort study that compared postoperative length of stay and postoperative direct cost among women on the enhanced recovery after surgery cesarean delivery pathway in the first year of implementation (April 1, 2017, to March 31, 2018; n=531) compared with historic controls (March 1, 2016, to February 28, 2017; n=661). Literature review informed the development of a prototype enhanced recovery after surgery pathway for cesarean delivery based on best practices from previous enhanced recovery after surgery experience in obstetrics (if available) or from other surgical disciplines if there were no available data for obstetrics. When there was not relevant published evidence from obstetrics, the taskforce used clinical experience and expert opinion to develop the pathway. The enhanced recovery after surgery cesarean delivery pathway included preadmission patient education and preoperative, intrapartum, and postoperative elements. Some components reflected standard obstetric care, and others were specific to the enhanced recovery after surgery pathway. Women with pregestational diabetes mellitus who were receiving insulin therapy before pregnancy, women with preeclampsia with severe features, women with complex pain needs, and women with surgical complications were excluded from baseline and implementation groups. Enhanced recovery after surgery cesarean delivery pathway participation was determined by order set usage. Analysis was stratified for women who underwent planned (no labor; n=530) and unplanned (labor; n=662) cesarean delivery. Demographic and clinical characteristics, postoperative length of stay, postoperative direct cost, and readmission rates for the baseline and implementation groups were compared with the use of chi-square and t-tests. RESULTS: During the first year of implementation, 531 of 640 eligible women (83%) were included in the enhanced recovery after surgery cesarean delivery pathway. Body mass index was marginally higher in the baseline group for unplanned cesarean delivery (32.5±7.1 vs 31.4±6.7 kg/m2; P=.04). Otherwise there were no significant differences in demographic or maternal clinical characteristics between baseline or implementation groups overall or for planned or unplanned cesarean delivery. Compared with baseline, implementation of the enhanced recovery after surgery cesarean delivery pathway resulted in a significant decrease in postoperative length of stay by 7.8% or 4.86 hours overall (P<.001) and for both planned (P=.001) and unplanned (P=.002) cesarean delivery. Total postoperative direct costs decreased by 8.4% or $642.85 per patient overall (P<.001) and for both planned (P<.001) and unplanned (P<.001) cesarean delivery. There were no significant differences in readmission rates. CONCLUSION: Implementation of an enhanced recovery after surgery pathway for women who had planned or unplanned cesarean delivery was associated with significantly decreased postoperative length of stay and significant direct cost-savings per patient, without an increase in hospital readmissions. Given that cesarean delivery is 1 of the most common surgical procedures performed in the United States, positively impacting postoperative length of stay and direct cost for women who undergo cesarean delivery could have significant healthcare cost-savings.

Survey of Obstetrics and Gynecology Residents Regarding Pneumococcal Vaccination in Pregnancy: Education, Knowledge, and Barriers to Vaccination.

OBJECTIVE: The 23-valent pneumococcal vaccine is recommended for adults over 65 years of age and younger adults with certain medical conditions. The Centers for Disease Control and Prevention (CDC) state insufficient evidence to recommend routine pneumococcal vaccination during pregnancy, but the vaccine is indicated for pregnant women with certain medical conditions. We designed this project to gauge obstetrics and gynecology (OB/GYN) resident knowledge of maternal pneumococcal vaccination. METHODS: We administered a 22-question survey to OB/GYN residents about maternal pneumococcal vaccination. We performed descriptive analysis for each question. RESULTS: 238 OB/GYN residents responded. Overall, 69.3% of residents reported receiving vaccination education and 86.0% reported having ready access to vaccine guidelines and safety data. Most residents knew that asplenia (78.2%), pulmonary disease (77.3%), and HIV/AIDS (69.4%) are indications for vaccination but less knew that cardiovascular disease (45.0%), diabetes (35.8%), asthma (42.8%), nephrotic syndrome (19.7%), and renal failure (33.6%) are also indications for vaccination. CONCLUSION: OB/GYN residents are taught about vaccines and have ready access to vaccine guidelines and safety data. However, knowledge of indications for pneumococcal vaccination in pregnancy is lacking. Likely, the opportunity to vaccinate at-risk pregnant patients is being missed.

Beyond the Ivory Tower: A Comparison of Grades Across Academic and Community OB/GYN Clerkship Sites.

UNLABELLED: CONSTRUCT: Decentralized clinical education is the use of community facilities and community physicians to educate medical students. The theory behind decentralized clinical education is that academic and community sites will provide educational equivalency as determined by objective and subjective performance measures, while training more medical students and exposing students to rural or underserved communities. One of the major challenges of decentralized clinical education is ensuring site comparability in both learning opportunities and evaluation of students. BACKGROUND: Previous research has examined objective measures of student performance, but less is known about subjective performance measures, particularly in the field of obstetrics and gynecology (OB/GYN). This study explores the implications of clinical site on the adequacy of subjective and objective performance measures. APPROACH: This was a retrospective cohort study of 801 students in the University of Washington School of Medicine OB/GYN clerkship from 2008 to 2012. Academic sites included those with OB/GYN residency programs (n = 2) and community sites included those without residency programs (n = 29). The association between clerkship site and National Board of Medical Examiners (NBME) grade was assessed using linear regression and clinical and final grade using multinomial regression, estimating ß coefficient and relative risks (RR), respectively, and 95% confidence intervals (CIs), adjusting for gender, academic quarter of clerkship, and year of clerkship. RESULTS: There were no differences in NBME exam grades of students at academic sites (76.4 (7.3) versus 74.6 (8.0), ß = -0.11, 95% CI [1.35, 1.12] compared to community sites. For clinical grade, students at community sites were 2.4 times more likely to receive honors relative to high pass (RR 2.45), 95% CI [1.72, 3.50], and for final grade, students at community sites were 1.9 times more likely to receive honors relative to pass (RR 1.98), 95% CI [1.27, 3.09], and 1.6 times more likely to receive honors relative to high pass (RR 1.62), 95% CI [1.05, 2.50], compared to those at academic sites. CONCLUSIONS: Students at community sites receive higher clinical and final grades in the OB/GYN clerkship. This highlights a significant challenge in decentralized clinical education-ensuring site comparability in clinical grading, Further work should examine the differences in sites, as well as improve standardization of clinical grading. This also underscores an important consideration, as the final grade can influence medical school rank, nomination into honor societies, and ranking of residency applicants.

Plasma hydrogen sulfide, nitric oxide, and thiocyanate levels are lower during pregnancy compared to postpartum in a cohort of women from the Pacific northwest of the United States.

AIMS: Pregnancy alters multiple physiological processes including angiogenesis, vasodilation, inflammation, and cellular redox, which are partially modulated by the gasotransmitters hydrogen sulfide (H2S) and nitric oxide (NO). In this study, we sought to determine how plasma levels of H2S, NO, and the H2S-related metabolites thiocyanate (SCN-), and methanethiol (CH3SH) change during pregnancy progression. MATERIALS AND METHODS: Plasma was collected from 45 women at three points: 25-28 weeks gestation, 28-32 week gestation, and at ≥3 months postpartum. Plasma levels of H2S, SCN-, and CH3SH were measured following derivatization using monobromobimane followed by LC-MS/MS. Plasma NO was measured indirectly using the Griess reagent. KEY FINDINGS: NO and SCN- were significantly lower in women at 25-28 weeks gestation and 28-32 weeks gestation than postpartum while plasma H2S levels were significantly lower at 28-32 weeks gestation than postpartum. No significant differences were observed in CH3SH. SIGNIFICANCE: Previous reports demonstrated that the production of H2S and NO are stimulated during pregnancy, but we observed lower levels during pregnancy compared to postpartum. Previous reports on NO have been mixed, but given the related effects of H2S and NO, it is expected that their levels would be higher during pregnancy vs. postpartum. Future studies determining the mechanism for decreased H2S and NO during pregnancy will elucidate the role of these gasotransmitters during normal and pathological progression of pregnancy.

The Effects of Pregnancy on Amino Acid Levels and Nitrogen Disposition.

Limited data are available on the effects of pregnancy on the maternal metabolome. Therefore, the objective of this study was to use metabolomics analysis to determine pathways impacted by pregnancy followed by targeted confirmatory analysis to provide more powerful conclusions about metabolic alterations during pregnancy. Forty-seven pregnant women, 18-50 years of age were included in this study, with each subject serving as their own control. Plasma samples were collected between 25 and 28 weeks gestation and again ≥3 months postpartum for metabolomics analysis utilizing an HILIC/UHPLC/MS/MS assay with confirmatory targeted specific concentration analysis for 10 of the significantly altered amino acids utilizing an LC/MS assay. Principle component analysis (PCA) on metabolomics data clearly separated pregnant and postpartum groups and identified outliers in a preliminary assessment. Of the 980 metabolites recorded, 706 were determined to be significantly different between pregnancy and postpartum. Pathway analysis revealed three significantly impacted pathways, arginine biosynthesis (p = 2 × 10-5 and FDR = 1 × 10-3), valine, leucine, and isoleucine metabolism (p = 2 × 10-5 and FDR = 2 × 10-3), and xanthine metabolism (p = 4 × 10-5 and FDR = 4 × 10-3). Of these we focused analysis on arginine biosynthesis and branched-chain amino acid (BCAA) metabolism due to their clinical importance and interconnected roles in amino acid metabolism. In the confirmational analysis, 7 of 10 metabolites were confirmed as significant and all 10 confirmed the direction of change of concentrations observed in the metabolomics analysis. The data support an alteration in urea nitrogen disposition and amino acid metabolism during pregnancy. These changes could also impact endogenous nitric oxide production and contribute to diseases of pregnancy. This study provides evidence for changes in both the ammonia-urea nitrogen and the BCAA metabolism taking place during pregnancy.

Impact of Pregnancy and Vitamin A Supplementation on CYP2D6 Activity.

The mechanism of cytochrome P450 2D6 (CYP2D6) induction during pregnancy has not been evaluated in humans. This study assessed the changes in CYP2D6 and CYP3A activities during pregnancy and postpartum, and the effect of vitamin A administration on CYP2D6 activity. Forty-seven pregnant CYP2D6 extensive metabolizers (with CYP2D6 activity scores of 1 to 2) received dextromethorphan (DM) 30 mg orally as a single dose during 3 study windows (at 25 to 28 weeks of gestation, study day 1; at 28 to 32 weeks of gestation, study day 2; and at ≥3 months postpartum, study day 3). Participants were randomly assigned to groups with no supplemental vitamin A (control) or with supplemental vitamin A (10 000 IU/day orally for 3 to 4 weeks) after study day 1. Concentrations of DM and its metabolites, dextrorphan (DX) and 3-hydroxymorphinan (3HM), were determined from a 2-hour post-dose plasma sample and cumulative 4-hour urine sample using liquid chromatography-mass spectrometry. Change in CYP2D6 activity was assessed using DX/DM plasma and urine metabolic ratios. The activity change in CYP3A was also assessed using the 3HM/DM urine metabolic ratio. The DX/DM urine ratio was significantly higher (43%) in pregnancy compared with postpartum (P = .03), indicating increased CYP2D6 activity. The DX/DM plasma ratio was substantially higher in the participants, with an activity score of 1.0 during pregnancy (P = .04) compared with postpartum. The 3HM/DM urinary ratio was significantly higher (92%) during pregnancy, reflecting increased CYP3A activity (P = .02). Vitamin A supplementation did not change CYP2D6 activity during pregnancy; however, plasma all-trans retinoic acid (atRA) concentrations were positively correlated with increased CYP2D6 activity during pregnancy and postpartum. Further research is needed to elucidate the mechanisms of increased CYP2D6 activity during pregnancy.

Cesarean delivery rates and indications in pregnancies complicated by diabetes.

OBJECTIVE: Rates of pregestational (PGDM) and gestational diabetes (GDM), and their associated pregnancy complications, are rising. Pregnancies complicated by diabetes have increased cesarean delivery (CD) rates; however, there are limited data regarding the current rates of, and contributing factors to, these deliveries. The Robson Ten Group Classification System (TGCS) is a clinically relevant, standardized framework that can be used to evaluate and analyze cesarean rates. The objective of this study was to evaluate rates of, and indications for, intrapartum, unplanned CD among pregnancies complicated by diabetes, compared to normoglycemic (NG) pregnancies, in a large United States birth cohort. METHODS: This retrospective cohort study used chart-abstracted data on births between 24 and 42 weeks' gestation at 17 hospitals that contributed to the Obstetrical Care Outcome Assessment Program database between 01/2016 and 03/2019. The CD rate for NG pregnancies, and pregnancies complicated by gestational and PGDM was calculated and compared using the Robson TGCS. The indications for intrapartum CD in patients with term, singleton, vertex gestations without a prior cesarean were then analyzed. Univariate and multivariate logistic regression models were used to compare the cesarean rate and indications for CD, between the diabetic groups and the NG group. Results were adjusted for maternal age, BMI, neonatal birth weight, and insurance status, as well as clustering by hospital. RESULTS: A total of 86,381 pregnant people were included in the study cohort. Of these 76,272 (88.3%) were NG, 8591 (9.9%) had GDM, and 1518 (1.8%) had PGDM. Compared to NG patients, overall cesarean rates were higher in patients with GDM (40.3% vs. 29.7%; aOR 1.25, 95%CI 1.18-1.31) and PGDM (60.0% vs. 29.7%; aOR 2.53, 95%CI 2.04-3.13). This finding remained true when the cohort was restricted to term, singleton, vertex laboring patients without a prior cesarean; compared to NG patients, the cesarean rate was higher in patients with GDM (17.4% vs. 12.2%, aOR 1.37, 95%CI 1.29-1.45) and PGDM (26.0% vs. 12.2%, aOR 2.55, 95%CI 2.00-3.25). The cesarean rate for fetal indications was similar in the GDM (5.7%) and NG (4.4%) groups, while those patients with PGDM had a significantly higher rate (10.4%; aOR 2.01, 95%CI 1.43-2.83). Similarly, the rate of cesarean for labor dystocia in patients with PGDM was significantly higher than in NG patients (16.9% vs. 7.0%, and aOR 2.28, 95%CI 1.66-3.13) while patients with GDM had an intermediate rate (10.6% vs. 7.0%, aOR 1.49, 95%CI 1.40-1.57). CONCLUSIONS: The CD rate is significantly higher in pregnancies complicated by diabetes, particularly pregestational, compared to NG pregnancies. Despite controlling for maternal factors and birth weight, pregnancies complicated by diabetes are more likely to undergo an unplanned intrapartum cesarean secondary to labor dystocia than their NG counterparts, but only pregnancies complicated by PGDM have an increased risk of cesarean for fetal indications. More research is needed to understand whether this higher cesarean rate is due to factors intrinsic to diabetes in laboring patients or is due to a difference in the way clinicians manage diabetics in labor.

Could ultrasound midwifery training increase antenatal detection of congenital anomalies in Ghana?

BACKGROUND: As part of World Health Organization (WHO) 2016 updated antenatal care (ANC) guidelines routine ultrasonography is recommended, including to detect congenital anomalies. The Ghana Health Service (GHS) developed an in-service midwifery ultrasound training course in 2017, which includes fetal anomaly detection. Training rollout has been very limited. We sought to determine proportions of anomalies among neonates presenting to Tamale Teaching Hospital (TTH) that should be prenatally detectable by course-trained midwives in order to determine training program potential utility. METHODS: We analyzed data from a registry of neonates admitted to TTH with congenital anomaly diagnoses in 2016. We classified ultrasonographic detectability of anomalies at ≤13 and 14-23 weeks gestation, based on GHS course content and literature review. Secondary analysis included 2011-2015 retrospective chart review data. RESULTS: Eighty-five neonates with congenital anomalies were admitted to TTH in 2016. Seventy-three (86%) mothers received ≥1 ANC visit; 47 (55%) had at least one prenatal ultrasound, but only three (6%) were interpreted as abnormal. Sixteen (19%) and 26 (31%) of the anomalies should be readily detectable by course-trained midwives at ≤13 and 14-23 weeks gestation, respectively. When the 161 anomalies from 2011-2015 were also analyzed, 52 (21%) and 105 (43%) should be readily detectable at ≤13 and 14-23 weeks gestation, respectively. "Optimal conditions" (state-of-the-art equipment by ultrasonography-trained physicians) should readily identify 53 (22%) and 115 (47%) of the anomalies at ≤13 and 14-23 weeks gestation, respectively. CONCLUSION: Training Ghanaian midwives could substantially increase second trimester anomaly detection, potentially at proportions nearing highly resourced settings. Our data also highlight the need for refinement of the WHO antenatal ultrasonography recommendation for a scan before 24 weeks gestation for multiple purposes. Gestational dating accuracy requires first trimester scanning while fetal anomaly detection is more accurate during second trimester. Further specification will enhance guideline utility.

Plasma Retinoid Concentrations Are Altered in Pregnant Women.

Vitamin A is vital to maternal-fetal health and pregnancy outcomes. However, little is known about pregnancy associated changes in maternal vitamin A homeostasis and concentrations of circulating retinol metabolites. The goal of this study was to characterize retinoid concentrations in healthy women (n = 23) during two stages of pregnancy (25-28 weeks gestation and 28-32 weeks gestation) as compared to ≥3 months postpartum. It was hypothesized that plasma retinol, retinol binding protein 4 (RBP4), transthyretin and albumin concentrations would decline during pregnancy and return to baseline by 3 months postpartum. At 25-28 weeks gestation, plasma retinol (-27%), 4-oxo-13-cis-retinoic acid (-34%), and albumin (-22%) concentrations were significantly lower, and all-trans-retinoic acid (+48%) concentrations were significantly higher compared to ≥3 months postpartum in healthy women. In addition, at 28-32 weeks gestation, plasma retinol (-41%), retinol binding protein 4 (RBP4; -17%), transthyretin (TTR; -21%), albumin (-26%), 13-cis-retinoic acid (-23%) and 4-oxo-13-cis-retinoic acid (-48%) concentrations were significantly lower, whereas plasma all-trans-retinoic acid concentrations (+30%) were significantly higher than ≥3 months postpartum. Collectively, the data demonstrates that in healthy pregnancies, retinol plasma concentrations are lower, but all-trans-retinoic acid concentrations are higher than postpartum.

Video-Based Communication Assessment of Physician Error Disclosure Skills by Crowdsourced Laypeople and Patient Advocates Who Experienced Medical Harm: Reliability Assessment With Generalizability Theory.

BACKGROUND: Residents may benefit from simulated practice with personalized feedback to prepare for high-stakes disclosure conversations with patients after harmful errors and to meet American Council on Graduate Medical Education mandates. Ideally, feedback would come from patients who have experienced communication after medical harm, but medical researchers and leaders have found it difficult to reach this community, which has made this approach impractical at scale. The Video-Based Communication Assessment app is designed to engage crowdsourced laypeople to rate physician communication skills but has not been evaluated for use with medical harm scenarios. OBJECTIVE: We aimed to compare the reliability of 2 assessment groups (crowdsourced laypeople and patient advocates) in rating physician error disclosure communication skills using the Video-Based Communication Assessment app. METHODS: Internal medicine residents used the Video-Based Communication Assessment app; the case, which consisted of 3 sequential vignettes, depicted a delayed diagnosis of breast cancer. Panels of patient advocates who have experienced harmful medical error, either personally or through a family member, and crowdsourced laypeople used a 5-point scale to rate the residents' error disclosure communication skills (6 items) based on audiorecorded responses. Ratings were aggregated across items and vignettes to create a numerical communication score for each physician. We used analysis of variance, to compare stringency, and Pearson correlation between patient advocates and laypeople, to identify whether rank order would be preserved between groups. We used generalizability theory to examine the difference in assessment reliability between patient advocates and laypeople. RESULTS: Internal medicine residents (n=20) used the Video-Based Communication Assessment app. All patient advocates (n=8) and 42 of 59 crowdsourced laypeople who had been recruited provided complete, high-quality ratings. Patient advocates rated communication more stringently than crowdsourced laypeople (patient advocates: mean 3.19, SD 0.55; laypeople: mean 3.55, SD 0.40; P<.001), but patient advocates' and crowdsourced laypeople's ratings of physicians were highly correlated (r=0.82, P<.001). Reliability for 8 raters and 6 vignettes was acceptable (patient advocates: G coefficient 0.82; crowdsourced laypeople: G coefficient 0.65). Decision studies estimated that 12 crowdsourced layperson raters and 9 vignettes would yield an acceptable G coefficient of 0.75. CONCLUSIONS: Crowdsourced laypeople may represent a sustainable source of reliable assessments of physician error disclosure skills. For a simulated case involving delayed diagnosis of breast cancer, laypeople correctly identified high and low performers. However, at least 12 raters and 9 vignettes are required to ensure adequate reliability and future studies are warranted. Crowdsourced laypeople rate less stringently than raters who have experienced harm. Future research should examine the value of the Video-Based Communication Assessment app for formative assessment, summative assessment, and just-in-time coaching of error disclosure communication skills.

Effects of Practicing With and Obtaining Crowdsourced Feedback From the Video-Based Communication Assessment App on Resident Physicians' Adverse Event Communication Skills: Pre-post Trial.

BACKGROUND: US residents require practice and feedback to meet Accreditation Council for Graduate Medical Education mandates and patient expectations for effective communication after harmful errors. Current instructional approaches rely heavily on lectures, rarely provide individualized feedback to residents about communication skills, and may not assure that residents acquire the skills desired by patients. The Video-based Communication Assessment (VCA) app is a novel tool for simulating communication scenarios for practice and obtaining crowdsourced assessments and feedback on physicians' communication skills. We previously established that crowdsourced laypeople can reliably assess residents' error disclosure skills with the VCA app. However, its efficacy for error disclosure training has not been tested. OBJECTIVE: We aimed to evaluate the efficacy of using VCA practice and feedback as a stand-alone intervention for the development of residents' error disclosure skills. METHODS: We conducted a pre-post study in 2020 with pathology, obstetrics and gynecology, and internal medicine residents at an academic medical center in the United States. At baseline, residents each completed 2 specialty-specific VCA cases depicting medical errors. Audio responses were rated by at least 8 crowdsourced laypeople using 6 items on a 5-point scale. At 4 weeks, residents received numerical and written feedback derived from layperson ratings and then completed 2 additional cases. Residents were randomly assigned cases at baseline and after feedback assessments to avoid ordinal effects. Ratings were aggregated to create overall assessment scores for each resident at baseline and after feedback. Residents completed a survey of demographic characteristics. We used a 2×3 split-plot ANOVA to test the effects of time (pre-post) and specialty on communication ratings. RESULTS: In total, 48 residents completed 2 cases at time 1, received a feedback report at 4 weeks, and completed 2 more cases. The mean ratings of residents' communication were higher at time 2 versus time 1 (3.75 vs 3.53; P<.001). Residents with prior error disclosure experience performed better at time 1 compared to those without such experience (ratings: mean 3.63 vs mean 3.46; P=.02). No differences in communication ratings based on specialty or years in training were detected. Residents' communication was rated higher for angry cases versus sad cases (mean 3.69 vs mean 3.58; P=.01). Less than half of all residents (27/62, 44%) reported prior experience with disclosing medical harm to patients; experience differed significantly among specialties (P<.001) and was lowest for pathology (1/17, 6%). CONCLUSIONS: Residents at all training levels can potentially improve error disclosure skills with VCA practice and feedback. Error disclosure curricula should prepare residents for responding to various patient affects. Simulated error disclosure may particularly benefit trainees in diagnostic specialties, such as pathology, with infrequent real-life error disclosure practice opportunities. Future research should examine the effectiveness, feasibility, and acceptability of VCA within a longitudinal error disclosure curriculum.

Changes in erythrocyte membrane epoxyeicosatrienoic, dihydroxyeicosatrienoic, and hydroxyeicosatetraenoic acids during pregnancy.

AIMS: Pregnancy is associated with numerous changes in physiological and metabolic processes to ensure successful progression to full term. One such change is the alteration of arachidonic acid (AA) metabolism and formation of eicosanoids. This study explores the changes in AA metabolites formed through the cytochrome P450 mediated pathway to epoxyeicosatrienoic (EET), dihydroxyeicosatrienoic (DHET), and hydroxyeicosatetraenoic (HETE) acids which have been implicated in blood pressure regulation and inflammatory responses that are important for a healthy pregnancy. MAIN METHODS: The study determines circulating levels of EETs, DHETs and HETEs extracted from erythrocyte membranes and measured by mass spectroscopy during the progression of a normal pregnancy. Blood samples, from 25 women, were collected at three time points including 25-28 weeks gestation, 28-32 weeks gestation, and the non-pregnant control at 3-4 months postpartum. KEY FINDINGS: Results demonstrate that healthy pregnancy is associated with significant increases in 8,9-DHET, 11,12-DHET and 14,15-DHET and a decrease in trans 8,9-EET during 28-32 weeks gestation compared to 3-4 months postpartum. These differences are likely due to several mechanisms including an increase in soluble epoxide hydrolase activity, a decrease in glutathione conjugation, and altered cytochrome P450 enzyme expression and/or activity that occurs during pregnancy. SIGNIFICANCE: Metabolism of AA through the cytochrome P450 pathway generates physiologically important eicosanoids that could play an important role in the progression of a healthy pregnancy. Establishing the changes that occur during normal pregnancy may, in the future, help in early detection of pregnancy complications including preeclampsia.

Pilot study of a condensed communication skills workshop for gynecologic oncology fellows.

In gynecologic oncology (GO) fellowship, devoting sufficient time to learning communication skills can be challenging due to required time and logistics. A two day workshop was previously piloted at a single institution with GOs and found to be beneficial. We sought to implement that curriculum in a condensed form. We conducted two four-hour sessions with 4 GO fellows at a single institution over 4 months. Sessions consisted of a didactic in communication skills led by faculty with VitalTalk™ training, followed by application with a simulated patient. Cases were developed and previously used in a two-day workshop at another institution. Fellows were surveyed prior to both sessions and after the second session. Perceived confidence was assessed on a Likert scale (1 to 5). An improvement was defined by an increase of ≥1 in Likert score. All fellows reported that the educational quality of the sessions was "excellent," that the time in between sessions was "just right," allowing them to apply skills learned in the first session prior to the second. After both sessions, at least three of the four fellows reported an improvement in confidence in nearly 50% (10/21) of the communication topics assessed. GO fellows perceived improvements in communication skills with condensed half-day training seminars.

Randomized Trial of Smartphone-Based Evaluation for an Obstetrics and Gynecology Clerkship.

OBJECTIVE: We hypothesized that compared to paper evaluations, a smartphone-based quick response (QR) evaluation tool would improve timeliness of feedback, enhance efficacy of giving and receiving feedback, and be as easy to use. DESIGN: We performed a randomized controlled trial of student and instructor experience with two evaluation tools in the OB/GYN clerkship at University of Washington School of Medicine (UWSOM). Sites were randomized to the QR or paper tool; students at QR sites received individualized QR codes at the beginning of the clerkship. Instructors and students completed postintervention surveys regarding the evaluation tool and associated feedback. We compared responses between groups using chi-squared tests. SETTING: Participating clerkship sites included primary, tertiary, private practice and institutional settings affiliated with the University of Washington in the Washington, Wyoming, Alaska, Montana and Idaho region. PARTICIPANTS: Of the 29 OB/GYN UWSOM clerkship sites, 18 agreed to participate and were randomized. Of 29 eligible instructors, 25 (86%) completed the survey, with n = 18 using QR and n = 7 using paper. Of 161 eligible students, 102 (63%) completed the survey, with n = 54 using QR and n = 48 using paper. RESULTS: Compared to those using paper evaluations, instructors using QR evaluations were significantly more likely to agree that the evaluation tool was easy to understand (100% QR vs 43% paper, p = 0.002), the tool was effective in providing feedback (78% QR vs 29% paper, p = 0.002), and they felt comfortable approaching students with the tool (89% QR vs 43% paper, p = 0.002). Compared to those using paper evaluations, students using QR evaluations were less likely to agree the tool was effective in eliciting feedback (QR 43% vs paper 55%, p = 0.042). CONCLUSION: Instructors found QR evaluations superior to paper evaluations for providing feedback to medical students, whereas students found QR evaluations less effective for feedback.

Bariatric Surgery in Women of Childbearing Age, Timing Between an Operation and Birth, and Associated Perinatal Complications.

Importance: Metabolic changes after maternal bariatric surgery may affect subsequent fetal development. Many relevant perinatal outcomes have not been studied in this postoperative population, and the risks associated with short operation-to-birth (OTB) intervals have not been well examined. Objective: To examine the risk for perinatal complications in women with a history of bariatric surgery (postoperative mothers [POMs]) by comparing them with mothers without operations (nonoperative mothers [NOMs]) and examining the association of the OTB interval with perinatal outcomes. Design, Setting, and Participants: This investigation was a population-based retrospective cohort study (January 1, 1980, to May 30, 2013) at hospitals in Washington State. Data were collected from birth certificates and maternally linked hospital discharge data. Participants were all POMs and their infants (n = 1859) and a population-based random sample of NOMs and their infants frequency matched by delivery year (n = 8437). Exposures: Bariatric operation before birth or categories of OTB intervals. Main Outcomes and Measures: The primary outcomes were prematurity, neonatal intensive care unit (NICU) admission, congenital malformation, small for gestational age (SGA), birth injury, low Apgar score (≤8), and neonatal mortality. Poisson regression was used to compute relative risks (RRs) and 95% CIs, with adjustments for maternal body mass index, delivery year, socioeconomic status, age, parity, and comorbid conditions. Results: A total of 10 296 individuals were included in the analyses for this study. In the overall cohort, the median age was 29 years (interquartile range, 24-33 years). Compared with infants from NOMS, infants from POMs had a higher risk for prematurity (14.0% vs 8.6%; RR, 1.57; 95% CI, 1.33-1.85), NICU admission (15.2% vs 11.3%; RR, 1.25; 95% CI, 1.08-1.44), SGA status (13.0% vs 8.9%; RR, 1.93; 95% CI, 1.65-2.26), and low Apgar score (17.5% vs 14.8%; RR, 1.21; 95% CI, 1.06-1.37). Compared with infants from mothers with greater than a 4-year OTB interval, infants from mothers with less than a 2-year interval had higher risks for prematurity (11.8% vs 17.2%; RR, 1.48; 95% CI, 1.00-2.19), NICU admission (12.1% vs 17.7%; RR, 1.54; 95% CI, 1.05-2.25), and SGA status (9.2% vs 12.7%; RR, 1.51; 95% CI, 0.94-2.42). Conclusions and Relevance: Infants of mothers with a previous bariatric operation had a greater likelihood of perinatal complications compared with infants of NOMs. Operation-to-birth intervals of less than 2 years were associated with higher risks for prematurity, NICU admission, and SGA status compared with longer intervals. These findings are relevant to women with a history of bariatric surgery and could inform decisions regarding the optimal timing between an operation and conception.

Conservative Management of Invasive Placentation: Two Cases with Different Surgical Approaches.

Background When placenta accreta complicates a delivery, the typical management is to perform a cesarean hysterectomy. Other management strategies, including leaving the placenta in situ, have been attempted and supported in some cases. This may allow for an interval hysterectomy, which can potentially decrease average blood loss and/or allow a minimally invasive approach to the hysterectomy. Cases We present two cases of women with invasive placentation managed conservatively with interval hysterectomy. One woman was managed with robotic-assisted laparoscopic surgery and the other with an open surgical approach. Conclusion These cases highlight the successful use of conservative management for invasive placentation in two stable patients and showcase the novel use of a robotic-assisted laparoscopic surgery for management of invasive placentation.

Simultaneous prenatal ethanol and nicotine exposure affect ethanol consumption, ethanol preference and oxytocin receptor binding in adolescent and adult rats.

Ethanol consumption and smoking during pregnancy are common, despite the known adverse effects on the fetus. The teratogenicity of each drug independently is well established; however, the effects of concurrent exposure to ethanol and nicotine in preclinical models remain unclear. This study examined the impact of simultaneous prenatal exposure to both ethanol and nicotine on offspring ethanol preference behaviors and oxytocin system dynamics. Rat dams were given liquid diet (17% ethanol derived calories (EDC)) on gestational day (GD) 5 and 35% EDC from GD 6-20 and concurrently an osmotic minipump delivered nicotine (3-6mg/kg/day) from GD 4-postpartum day 10. Offspring were tested for ethanol preference during adolescence (postnatal day (PND) 30-43) and again at adulthood (PND 60-73), followed by assays for oxytocin mRNA expression and receptor binding in relevant brain regions. Prenatal exposure decreased ethanol preference in males during adolescence, and decreased consumption and preference in females during adulthood compared to controls. Oxytocin receptor binding in the nucleus accumbens and hippocampus was increased in adult prenatally exposed males only. Prenatal exposure to these drugs sex-specifically decreased ethanol preference behavior in offspring unlike reports for either drug separately. The possible role of oxytocin in reduction of ethanol consumption behavior is highlighted.