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Background The purpose of this study was to estimate prevalence of asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among patients admitted to obstetric inpatient units throughout the United States as detected by universal screening. We sought to describe the relationship between obstetric inpatient asymptomatic infection rates and publicly available surrounding community infection rates. Methods A cross-sectional study in which medical centers reported rates of positive SARS-CoV-2 testing in asymptomatic pregnant and immediate postpartum patients over a 1–3-month time span in 2020. Publicly reported SARS-CoV-2 case rates from the relevant county and state for each center were collected from the COVID Act Now dashboard and the COVID Tracking Project for correlation analysis. Results Data were collected from 9 health centers, encompassing 18 hospitals. Participating health centers were located in Alabama, California, Illinois, Louisiana, New Jersey, North Carolina, Pennsylvania, Rhode Island, Utah, and Washington State. Each hospital had an active policy for universal SARS-CoV-2 testing on obstetric inpatient units. A total of 10 147 SARS-CoV-2 tests were administered, of which 124 were positive (1.2%). Positivity rates varied by site, ranging from 0–3.2%. While SARS-CoV-2 infection rates were lower in asymptomatic obstetric inpatient groups than the surrounding communities, there was a positive correlation between positivity rates in obstetric inpatient units and their surrounding county (P=.003, r=.782) and state (P=.007, r=.708). Conclusions Given the correlation between community and obstetric inpatient rates, the necessity of SARS-CoV-2–related healthcare resource utilization in obstetric inpatient units may be best informed by surrounding community infection rates., There was a significant positive correlation between SARS-CoV-2 positivity rates in obstetric inpatient units and their surrounding county and state. Healthcare resource utilization related to SARS-CoV-2 testing in obstetric inpatient units may be best informed by surrounding community infection rates.

OBJECTIVE To characterize trends of an influenza diagnosis at delivery hospitalization and its association with severe maternal morbidity. METHODS We conducted a repeated cross-sectional analysis of delivery hospitalizations using the Nationwide Inpatient Sample from 2000 to 2018. We assessed the association between an influenza diagnosis at delivery hospitalization and severe maternal morbidity excluding transfusion per Centers for Disease Control and Prevention criteria. Secondary outcomes included maternal death and morbidity measures associated with influenza (mechanical intubation and ventilation, sepsis and shock, and acute respiratory distress syndrome [ARDS]) and obstetric complications (preterm birth and hypertensive disorders of pregnancy). We assessed trends of severe maternal morbidity by annual influenza season and the association between influenza and severe maternal morbidity using multivariable log-linear regression, adjusting for demographic, clinical, and hospital characteristics. RESULTS Of 74.7 million delivery hospitalizations, 23 per 10,000 were complicated by an influenza diagnosis. The rate of severe maternal morbidity was higher with an influenza diagnosis compared with those without influenza (86-410 cases vs 53-70 cases/10,000 delivery hospitalizations). Women with an influenza diagnosis at delivery hospitalization were at an increased risk of severe maternal morbidity compared with those without influenza (2.3 vs 0.7%; adjusted risk ratio 2.24, 95% CI 2.17-2.31). This association held for maternal death, mechanical intubation, sepsis and shock, and ARDS-as well as obstetric complications, including preterm birth and hypertensive disorders of pregnancy. CONCLUSION Pregnant women with influenza are at increased risk of severe maternal morbidity, as well as influenza-related maternal and obstetric complications. These results emphasize the importance of primary prevention and recognition of influenza infection during pregnancy to reduce downstream maternal morbidity and mortality.

A paucity of data exists about the current practice of fetal red blood cell (RBC) transfusion in the United States (US). This investigation describes intrauterine transfusion (IUT) RBC product selection and processing practices at different US institutions.A transfusion medicine and maternal-fetal medicine (MFM) team designed a survey to interrogate and characterize RBCs utilized for IUT. This survey was distributed to seventy US institutions with fetal treatment centers (October 2020-April 2021) identified through the NAFTNet (North American Fetal Therapy Network).Thirty-seven institutions responded (response rate 53%, 37/70), but five were excluded for not performing IUTs. Most (84%; 27/32) performed 1-24 IUTs annually; two performed50 IUTs/year. Group O, Rh(D) negative RBC units were always used by 66% (21/32), and 75% (24/32) provided hemoconcentrated RBCs by washing (17/24) or dry packing (6/24). Overall, 66% (21/32) targeted a hematocrit ≥75%. Fifty percent provided both leukocyte-reduced and CMV-negative RBC units. Irradiation of RBC units was performed within 6 h of issue at 63% (20/32) of sites. Most (81%, 26/32) used RBC units at7 days of age after collection, 56% (18/32) always provided washed RBC units, while 19% (6/32) issued washed RBC only if fresh units are unavailable. Implicated maternal RBC alloantibodies were matched for 78% (25/32) of the time. The transfused volume was universally determined by the MFMs.Heterogeneity and lack of standardization exist in RBC product selection and special processing steps for IUTs in the US. Hence, the establishment of a consensus to standardize IUT protocols is needed.

Chromosomal abnormalities are associated with changes in complex aspects of chorionic villi histomorphology. This study used a simple scoring system to evaluate the association between atypical gross morphology and abnormal chromosomal testing on chorionic villus sampling (CVS). This retrospective cohort study included singleton pregnancies that underwent CVS at a single institution from 2006-2017. The degree of budding, branching, and vascularity (BBV) was scored from 0 to 3 for each CVS specimen, and individual scores were summed to calculate a composite BBV score. Scores were categorized into typical or atypical based on the cohort's distribution. The primary predictor was atypical BBV score, and the primary outcome was chromosomal abnormality. Fisher's exact test compared proportions, and logistic regression generated odds ratios. Among 1171 CVS specimens, 28% had chromosomal abnormalities. The chromosomally abnormal group had a higher rate of atypical BBV score than the normal group (7.3% vs 3.7%, P=0.009), a finding that remained statistically significant after controlling for maternal age, gestational age, and mode of CVS (aOR 2.2, 95% CI 1.24-3.82). Atypical chorionic villus morphology is associated with chromosomal abnormalities. This scoring system is simple, rapid, and easy to perform at the time of routine diagnosis.

Objective Although preterm delivery (PTD) before 34 weeks for severe hypertensive disease is a diagnostic criterion for antiphospholipid syndrome (APS), there is no consensus regarding testing for antiphospholipid antibodies (aPL) in this setting. We aim to describe the frequency of and the characteristics associated with inpatient aPL testing in this population. Study Design In this retrospective study of PTD before 34 weeks for severe hypertensive disease, charts were reviewed for aPL testing, gestational age at delivery, fetal complications, and severity of maternal disease. Wilcoxon rank-sum test, Fisher's exact, and chi-squared tests were used for analyses of continuous and categorical variables, and multivariate logistic regression for adjusted odds ratios. Results Among 133 cases, 14.3% had APS screening via aPL testing. Screened patients delivered earlier than unscreened patients (28.9 vs. 31.7 weeks, p Conclusion APS screening after PTD for severe hypertensive disease is uncommon but more likely with earlier PTD. Despite conflicting recommendations from professional organizations, prior studies demonstrate contraceptive, obstetrical, and long-term risks associated with APS, suggesting that we should increase our screening efforts.

ObjectiveTo analyse trends, risk factors, and outcomes related to hypertensive disorders of pregnancy (HDP).DesignRepeated cross-sectional.SettingUS delivery hospitalisations.PopulationDelivery hospitalisations in the 2000-2018National Inpatient Sample.MethodsUS hospital delivery hospitalisations with HDP were analysed. Several trends were analysed: (i) the proportion of deliveries by year with HDP, (ii) the proportion of deliveries with HDP risk factors and (iii) adverse outcomes associated with HDP including maternal stroke, acute renal failure and acute liver injury. Risk ratios were determined using regression models with HDP as the exposure of interest.Main outcome measuresPrevalence of HDP, risk factors for HDP and associated adverse outcomes.ResultsOf 73.1million delivery hospitalisations, 7.7% had an associated diagnosis of HDP. Over the study period, HDP doubled from 6.0% of deliveries in 2000 to 12.0% in 2018. The proportion of deliveries with risk factors for HDP increased from 9.6% in 2000 to 24.6% in 2018. In adjusted models, HDP were associated with increased stroke (aRR [adjusted risk ratio] 15.9, 95% CI 14.8-17.1), acute renal failure (aRR 13.8, 95% CI 13.5-14.2) and acute liver injury (aRR 1.2, 95% CI 1.2-1.3). Among deliveries with HDP, acute renal failure and acute liver injury increased; in comparison, stroke decreased.ConclusionHypertensive disorders of pregnancy increased in the setting of risk factors for HDP becoming more common, whereas stroke decreased.Tweetable abstractWhile hypertensive disorders of pregnancy increased from 2000 to 2018, stroke appears to be decreasing.

Maternal cardiac disease (MCD) is associated with increased maternal and neonatal morbidity and mortality. Because unplanned pregnancies are especially risky, active use of reliable contraception is critical in this population. Studies in the noncardiac population have demonstrated that the postpartum period is an ideal time to address contraceptive plans. This retrospective cohort study was designed to describe contraceptive choices in women with MCD in the immediate postpartum period and to identify factors associated with specific contraceptive plans. We included women with MCD who delivered from January 2008 to September 2017 at a tertiary care institution with a multidisciplinary obstetrics and cardiology team. Maternal demographics, specifics of MCD, obstetrical outcomes, and contraceptive plans were obtained through chart review. Contraceptive plans were categorized into highly reliable methods (sterilization or long-acting reversible contraceptive methods) or less reliable methods (nonlong-acting reversible contraceptive methods or no contraception). In the 254 women included in this study, 40% planned to use highly reliable methods, while 60% planned to use less reliable methods. Women with cardiomyopathy were more likely to choose a highly reliable method of contraception (adjusted odds ratio 2.6, 95% confidence interval 1.2 to 5.7), a reassuring finding, given the particularly high risk of poor pregnancy outcome with this diagnosis. There were no differences in other cardiac diagnoses between the 2 contraceptive groups. In conclusion, the finding that

ObjectiveMonochorionic, diamniotic (MCDA) twin pairs are predisposed to various pregnancy complications due to the unique placental angioarchitecture of monochorionicity. Few studies have evaluated the outcomes of weight-discordant MCDA pairs without selective fetal growth restriction (SFGR) or the risk factors for development of SFGR. This study aims to describe the natural history of expectant, noninvasive management of weight-discordant MCDA twins and to evaluate risk factors associated with progression to SFGR.Study designThis was a retrospective cohort study at a single, tertiary care center in the United States. All MCDA twins with isolated intertwin weight discordance (ITWD) ≥ 20% diagnosed before 26 weeks' gestational age (GA) were included. The primary outcome of descriptive analyses was overall pregnancy outcome, incorporating both survival to delivery and GA at delivery, as defined by the North American Fetal Therapy Network. The secondary outcome was SFGR in one twin (defined as estimated fetal weight

To characterize trends of an influenza diagnosis at delivery hospitalization and its association with severe maternal morbidity.We conducted a repeated cross-sectional analysis of delivery hospitalizations using the Nationwide Inpatient Sample from 2000 to 2018. We assessed the association between an influenza diagnosis at delivery hospitalization and severe maternal morbidity excluding transfusion per Centers for Disease Control and Prevention criteria. Secondary outcomes included maternal death and morbidity measures associated with influenza (mechanical intubation and ventilation, sepsis and shock, and acute respiratory distress syndrome [ARDS]) and obstetric complications (preterm birth and hypertensive disorders of pregnancy). We assessed trends of severe maternal morbidity by annual influenza season and the association between influenza and severe maternal morbidity using multivariable log-linear regression, adjusting for demographic, clinical, and hospital characteristics.Of 74.7 million delivery hospitalizations, 23 per 10,000 were complicated by an influenza diagnosis. The rate of severe maternal morbidity was higher with an influenza diagnosis compared with those without influenza (86-410 cases vs 53-70 cases/10,000 delivery hospitalizations). Women with an influenza diagnosis at delivery hospitalization were at an increased risk of severe maternal morbidity compared with those without influenza (2.3 vs 0.7%; adjusted risk ratio 2.24, 95% CI 2.17-2.31). This association held for maternal death, mechanical intubation, sepsis and shock, and ARDS-as well as obstetric complications, including preterm birth and hypertensive disorders of pregnancy.Pregnant women with influenza are at increased risk of severe maternal morbidity, as well as influenza-related maternal and obstetric complications. These results emphasize the importance of primary prevention and recognition of influenza infection during pregnancy to reduce downstream maternal morbidity and mortality.

Background: The purpose of this study was to estimate prevalence of asymptomatic SARS-CoV-2 infection among patients admitted to obstetric inpatient units throughout the United States as detected by universal screening. We sought to describe the relationship between obstetric inpatient asymptomatic infection rates and publicly available surrounding community infection rates. Methods: This was a cross-sectional study in which medical centers reported rates of positive SARS-CoV-2 testing in asymptomatic pregnant and immediate postpartum patients over a 1-3 month time span in 2020. Publicly reported SARS-CoV-2 case rates from the relevant county and state for each center were collected from the COVID Act Now dashboard and the COVID Tracking Project for correlation analysis. Findings: Data were collected from nine health centers, encompassing 18 hospitals. Participating health centers were located in Alabama, California, Illinois, Louisiana, New Jersey, North Carolina, Pennsylvania, Rhode Island, Utah, and Washington State. Each hospital had an active policy for universal SARS-CoV-2 testing on obstetric inpatient unit. A total of 10,147 SARS-CoV-2 tests were administered, of which 124 were positive (1·2%). Positivity rates varied by site, ranging from 0-3·2%. While SARS-CoV-2 infection rates were lower in asymptomatic obstetric inpatient groups than the surrounding communities, there was a positive correlation between positivity rates in obstetric inpatient units and their surrounding county (p=·003, r=·782) and state (p=·007, r=·708). Interpretation: Given the correlation between community and obstetric inpatient rates, the necessity of SARS-CoV-2 related healthcare resource utilization in obstetric inpatient units may be best-informed by surrounding community infection rates. Funding Information: Internal funding was used. Declaration of Interests: None to declare. Ethics Approval Statement: The study was IRB approved or determined exempt at each center.

Objective A prominent randomized controlled trial demonstrated that low-dose misoprostol with the concurrent cervical Foley shortened the median time to delivery when compared with either method alone. Our study aims to address implementation of this protocol and evaluate its impact on time to delivery. Study Design This was a retrospective before-and-after study of nulliparous women who delivered nonanomalous, term, singletons at the University of California San Francisco (UCSF) in two separate 2-year periods before and after changes in UCSF's cervical ripening protocol. The primary outcome was time from first misoprostol dose to delivery. Results A total of 1,496 women met inclusion criteria, with 698 in the preimplementation group and 798 in the postimplementation group. There were no statistically significant differences in time to delivery (29 vs. 30 hours, p = 0.69), rate of cesarean delivery (30 vs. 26%, p = 0.09), or cesarean delivery for fetal indications (11 vs. 8%, p = 0.15) between the groups. Conclusion Implementing evidence-based low-dose misoprostol with the concurrent cervical Foley did not change the time to delivery, time to vaginal-delivery, or likelihood of vaginal delivery in our population. This may be due to differences in labor management practices and incomplete fidelity to the protocol. Real-world effectiveness of these interventions will vary and should be considered when choosing an induction method.

A 37-year-old woman presented with chest pain and shortness of breath in the third trimester of pregnancy. Diagnostic imaging demonstrated a saddle pulmonary embolism, severe impairment of right ventricular function, and an extensive deep venous thrombus. She underwent catheter-directed thrombolysis with tissue plasminogen activator and delivered a healthy infant at term. (Level of Difficulty: Intermediate.), Graphical abstract

Chromosomal abnormalities are associated with changes in complex aspects of chorionic villi histomorphology. This study used a simple scoring system to evaluate the association between atypical gross morphology and abnormal chromosomal testing on chorionic villus sampling (CVS). This retrospective cohort study included singleton pregnancies that underwent CVS at a single institution from 2006-2017. The degree of budding, branching, and vascularity (BBV) was scored from 0 to 3 for each CVS specimen, and individual scores were summed to calculate a composite BBV score. Scores were categorized into typical or atypical based on the cohort's distribution. The primary predictor was atypical BBV score, and the primary outcome was chromosomal abnormality. Fisher's exact test compared proportions, and logistic regression generated odds ratios. Among 1171 CVS specimens, 28% had chromosomal abnormalities. The chromosomally abnormal group had a higher rate of atypical BBV score than the normal group (7.3% vs 3.7%, P=0.009), a finding that remained statistically significant after controlling for maternal age, gestational age, and mode of CVS (aOR 2.2, 95% CI 1.24-3.82). Atypical chorionic villus morphology is associated with chromosomal abnormalities. This scoring system is simple, rapid, and easy to perform at the time of routine diagnosis.

BACKGROUND Chronic comorbid conditions increase the risk of influenza-related morbidity. Whether this holds for pregnant women who are at a high risk of complications from influenza remains to be determined. OBJECTIVE This study aimed to determine whether chronic comorbid conditions are associated with an increased risk of severe maternal morbidity among pregnant women with an influenza diagnosis at delivery hospitalization. STUDY DESIGN We performed a cross-sectional analysis of delivery hospitalizations complicated by an influenza diagnosis using the National Inpatient Sample from 2000 to 2015. We assessed 4 prevalent chronic comorbid conditions associated with increased influenza complications outside of pregnancy, obstructive lung disease (asthma and chronic obstructive pulmonary disease), chronic hypertension, obesity, and pregestational diabetes mellitus, overall and individually. The primary outcome was severe maternal morbidity, excluding transfusion as defined by the Centers for Disease Control and Prevention, and the secondary outcomes were specific severe maternal morbidity measures that were recognized as influenza-related complications, acute respiratory distress syndrome, mechanical intubation and ventilation, and sepsis and shock. Multivariable survey-weighted log-linear models were used, adjusting for patient, hospital, and clinical characteristics. RESULTS Of 62.7 million delivery hospitalizations, 144,572 (0.2%) were complicated by an influenza diagnosis at delivery hospitalization (23 cases of influenza per 10,000 delivery hospitalizations) and 36,054 (24.9%) with ≥1 chronic comorbid conditions, of which 77.4% included obstructive lung disease. Pregnant women with an influenza diagnosis at delivery hospitalization with chronic comorbid conditions had a slightly higher risk of severe maternal morbidity than those without (2.6% vs 1.7%; adjusted risk ratio, 1.11; 95% confidence interval, 1.03–1.21) and acute respiratory distress syndrome (0.9% vs 0.5%; adjusted risk ratio, 1.42; 95% confidence interval, 1.23–1.64) and mechanical intubation and ventilation (0.2% vs 0.1%; adjusted risk ratio, 1.92; 95% confidence interval, 1.37–2.69) but a lower risk of sepsis and shock (0.2% vs 0.3%; adjusted risk ratio, 0.57; 95% confidence interval, 0.45–0.73). Regarding specific conditions, obstructive lung disease was associated with an increased risk of severe maternal morbidity (adjusted risk ratio, 1.21; 95% confidence interval, 1.11–1.32) and acute respiratory distress syndrome (adjusted risk ratio, 1.54; 95% confidence interval, 1.32–1.79) and mechanical intubation and ventilation (adjusted risk ratio, 2.80; 95% confidence interval, 2.00–3.91). Chronic hypertension was associated with an increased risk of acute respiratory distress syndrome (adjusted risk ratio, 1.70; 95% confidence interval, 1.16–2.49) but a lower risk of sepsis and shock (adjusted risk ratio, 0.34; 95% confidence interval, 0.13–0.85). Obesity was associated with a lower risk of severe maternal morbidity (adjusted risk ratio, 0.84; 95% confidence interval, 0.74–0.97). Pregestational diabetes mellitus was not associated with severe maternal morbidity. CONCLUSION Among women with a diagnosis of influenza at delivery hospitalization, chronic comorbid conditions may increase the risk of severe maternal morbidity and particularly outcomes related to influenza. These results can inform efforts to increase influenza vaccination for all pregnant women, in particular those with chronic comorbidities.

Background There are limited data on the natural history of antenatal Zika virus (ZIKV) exposure in twin pregnancies, especially regarding intertwin concordance of prenatal, placental, and infant outcomes. Methods This prospective cohort study included twin pregnancies referred to a single institution from September 2015 to June 2016 with maternal ZIKV. Polymerase chain reaction (PCR) testing of maternal, placental, and neonatal samples was performed. Prenatal ultrasounds were completed for each twin, and histomorphologic analysis was performed for each placenta. Abnormal neonatal outcome was defined as abnormal exam and/or abnormal imaging. Two- to three-year follow-up of infants included physical exams, neuroimaging, and Bayley-III developmental assessment. Results Among 244 pregnancies, 4 twin gestations without coinfection were identified. Zika virus infection occurred at 16–33 weeks gestation. Zika virus PCR testing revealed discordance between dichorionic twins, between placentas in a dichorionic pair, between portions of a monochorionic placenta, and between a neonate and its associated placenta. Of the 8 infants, 3 (38%) had an abnormal neonatal outcome. Of 6 infants with long-term follow-up, 3 (50%) have demonstrated ZIKV-related abnormalities. Conclusions Neonatal PCR testing, placental findings, and infant outcomes can be discordant between co-twins with antenatal ZIKV exposure. These findings demonstrate that each twin should be evaluated independently for vertical transmission.

Preterm birth is the leading cause of neonatal morbidity and death in the United States. Although many risk factors for spontaneous preterm birth have been elucidated, some women with a previous term delivery experience spontaneous preterm birth in the absence of any identifiable risk factors. Cervical trauma during a prolonged second stage of labor has been postulated as a potential contributor to subsequent spontaneous preterm birth.This study was designed to examine the relationship between the length of the second stage of labor in the first pregnancy and the risk of spontaneous preterm birth in the subsequent pregnancy.This was a retrospective cohort study of all women with 2 consecutive singleton deliveries at a single institution between July 2012 and June 2018, with the first delivery occurring ≥37 weeks of gestation. Multiparous women and those women who did not reach the second stage of labor in the first pregnancy were excluded. Prolonged second stage of labor was defined as ≥4 hours, based on the 75th percentile for this cohort and on recommendations from the National Institute of Child Health and Human Development. Very prolonged second stage of labor was defined as ≥7 hours, based on the 95th percentile for this cohort. The primary outcome was spontaneous preterm birth37 weeks of gestation in the subsequent pregnancy. The Kruskal-Wallis test compared median values for nonparametric continuous variables; Fisher's exact tests compared proportions for categoric variables, and logistic regression generated odds ratios.A total of 1032 women met criteria for study inclusion, with an overall subsequent spontaneous preterm birth rate of 3.1%. Prolonged second stage of labor of ≥4 hours was identified in 24.4% (252/1032 women) of the cohort, with 70.6% (178/252 women) of this group delivering vaginally. There was no statistically significant difference in rate of spontaneous preterm birth in those with and without prolonged second stage of labor (4.4% [11/252 women] with prolonged labor vs 2.7% [21/780 women] without prolonged labor; P=.21; odds ratio, 1.6; 95% confidence interval, 0.8-3.5). Very prolonged second stage of labor of ≥7 hours was identified in 4.3% (44/1032 women) of the cohort, with 45.4% (20/44 women) of this group delivering vaginally. There was a significantly higher rate of spontaneous preterm birth in those with very prolonged second stage of labor compared with those without prolonged labor (9.1% [4/44 women] with prolonged labor vs 2.8% [28/988 women] without prolonged labor; P=.04; odds ratio, 3.4; 95% confidence interval, 1.1-10.2), although this finding did not persist after we controlled for the mode of first delivery (adjusted odds ratio, 1.55; 95% confidence interval, 0.65-3.73). Spontaneous preterm birth after very prolonged second stage of labor was identified in only 4 patients, all of whom had a cesarean delivery with the first pregnancy.A second stage of labor of ≥4 hours in the first pregnancy was not associated with an increased risk of subsequent spontaneous preterm birth and was associated with a high rate (70%) of vaginal birth. A second stage of labor of ≥7 hours did not appear to be associated with an increased risk of preterm birth, when we adjusted for mode of first delivery. There was a nonsignificant increase in the risk of preterm birth in those who delivered via cesarean section after a second stage of labor of ≥7 hours.

The modified World Health Organization (mWHO) classification is known to estimate the risk of maternal cardiovascular (CV) events in pregnancy and up to 6 months (mo) postpartum among women with congenital heart disease (CHD). However, predictors of maternal CV events > 6 mo after delivery have not

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.

SummaryEstrogens regulate body weight and reproduction primarily through actions on estrogen receptor-α (ERα). However, ERα-expressing cells mediating these effects are not identified. We demonstrate that brain-specific deletion of ERα in female mice causes abdominal obesity stemming from both hyperphagia and hypometabolism. Hypometabolism and abdominal obesity, but not hyperphagia, are recapitulated in female mice lacking ERα in hypothalamic steroidogenic factor-1 (SF1) neurons. In contrast, deletion of ERα in hypothalamic pro-opiomelanocortin (POMC) neurons leads to hyperphagia, without directly influencing energy expenditure or fat distribution. Further, simultaneous deletion of ERα from both SF1 and POMC neurons causes hypometabolism, hyperphagia, and increased visceral adiposity. Additionally, female mice lacking ERα in SF1 neurons develop anovulation and infertility, while POMC-specific deletion of ERα inhibits negative feedback regulation of estrogens and impairs fertility in females. These results indicate that estrogens act on distinct hypothalamic ERα neurons to regulate different aspects of energy homeostasis and reproduction.

Background Specialized hypothalamic systems that increase food intake might also increase ethanol intake. To test this possibility, morphine and receptor-specific opioid agonists were microinjected in the paraventricular nucleus (PVN) of rats that had learned to drink ethanol. To cross-validate the results, naloxone methiodide (m-naloxone), an opioid antagonist, was microinjected with the expectation that it would have the opposite effect of morphine and the specific opioid agonists. Methods Sprague-Dawley rats were trained, without sugar, to drink 4 or 7% ethanol and were then implanted with chronic brain cannulas aimed at the PVN. After recovery, those drinking 7% ethanol, with food and water available, were injected with 2 doses each of morphine or m-naloxone. To test for receptor specificity, 2 doses each of the mu-receptor agonist [D-Ala(2),N-Me-Phe(4),Gly(5)-ol]-Enkephalin (DAMGO), delta-receptor agonist D-Ala-Gly-Phe-Met-NH2 (DALA), or kappa-receptor agonist U-50,488H were injected. DAMGO was also tested in rats drinking 4% ethanol without food or water available. As an anatomical control for drug reflux, injections were made 2 mm dorsal to the PVN. Results A main result was a significant increase in ethanol intake induced by PVN injection of morphine. The opposite effect was produced by m-naloxone. The effects of morphine and m-naloxone were exclusively on intake of ethanol, even though food and water were freely available. In the analysis with specific receptor agonists, PVN injection of the delta-agonist DALA significantly increased 7% ethanol intake without affecting food or water intake. This is in contrast to the kappa-agonist U-50,488H, which decreased ethanol intake, and the mu-agonist DAMGO, which had no effect on ethanol intake in the presence or absence of food and water. In the anatomical control location 2 mm dorsal to the PVN, no drug caused any significant changes in ethanol, food, or water intake, providing evidence that the active site was close to the cannula tip. Conclusions The delta-opioid receptor agonist in the PVN increased ethanol intake in strong preference over food and water, while the kappa-opioid agonist suppressed ethanol intake. Prior studies show that learning to drink ethanol stimulates PVN expression and production of the peptides enkephalin and dynorphin, which are endogenous agonists for the delta- and kappa-receptors, respectively. These results suggest that enkephalin via the delta-opioid system can function locally within a positive feedback circuit to cause ethanol intake to escalate and ultimately contribute to the abuse of ethanol. This is in contrast to dynorphin via the kappa-opioid system, which may act to counter this escalation. Naltrexone therapy for alcoholism may act, in part, by blocking the enkephalin-triggered positive feedback cycle.

The nucleus accumbens (NAc) participates in the control of both motivation and addiction. To test the possibility that opioids in the NAc can cause rats to select ethanol in preference to food, Sprague–Dawley rats with ethanol, food, and water available, were injected with two doses each of morphine, the μ-receptor agonist [D-Ala 2 ,N-Me-Phe 4 ,Gly 5 -ol]-Enkephalin (DAMGO), the δ -receptor agonist D-Ala-Gly-Phe-Met-NH2 (DALA), the k-receptor agonist (±)- trans -U-50488 methanesulfonate (U-50,488H), or the opioid antagonist naloxone methiodide (m-naloxone). As an anatomical control for drug reflux, injections were also made 2 mm above the NAc. The main result was that morphine in the NAc significantly increased ethanol and food intake, whereas m-naloxone reduced ethanol intake without affecting food or water intake. Of the selective receptor agonists, DALA in the NAc increased ethanol intake in preference to food. This is in contrast to DAMGO, which stimulated food but not ethanol intake, and the k-agonist U-50,488H, which had no effect on intake. When injected in the anatomical control site 2 mm dorsal to the NAc, the opioids had no effects on ethanol intake. These results demonstrate that ethanol intake produced by morphine in the NAc is driven in large part by the δ -receptor. In light of other studies showing ethanol intake to increase enkephalin expression in the NAc, the present finding of enkephalin-induced ethanol intake suggests the existence of a positive feedback loop that fosters alcohol abuse. Naltrexone therapy for alcohol abuse may then act, in part, in the NAc by blocking this opioid-triggered cycle of alcohol intake.