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Background: We tested the hypothesis that women who develop gestational hypertension (GH) display abnormal sympathetic action potential (AP) discharge patterns during late pregnancy (32–36 weeks), both at supine rest and during postural stress. Methods: Thirteen nonpregnant, female controls (nonpregnant controls [CTRL]) and 32 pregnant women participated; 14 had low-risk (no personal history of GH) normal pregnancies (LR-NP), 10 had high-risk (personal history of GH) normal pregnancies (HR-NP), and 8 developed GH. We measured heart rate, blood pressure, and muscle sympathetic nerve activity (microneurography) at supine rest and 60° head-up tilt. Sympathetic AP patterns were studied using wavelet-based methodology. Results: At rest, muscle sympathetic nerve activity burst frequency was elevated in LR-NP, HR-NP, and GH versus CTRL (all P ≤0.01); however, the AP content per integrated burst was augmented only in GH (20±5 spikes/burst), compared with CTRL (8±3 spikes/burst), LR-NP (9±2 spikes/burst) and HR-NP (11±4 spikes/burst; all P P 2 =46%) and diastolic (R 2 =20%) blood pressure (both P ≤0.01). Unlike CTRL (both P P =0.71) or recruit latent subpopulations of larger-sized APs ( P =0.72) in response to head-up tilt, perhaps related to a ceiling-effect; however, total AP firing frequency in the upright posture was elevated in the GH cohort versus CTRL, LR-NP, and HR-NP (all P Conclusions: Women who develop GH display aberrant sympathetic AP firing patterns in both the supine and upright postures.

Supplementary Table 2. Odds ratios and 95% confidence intervals for individual-level factors controlled for in the original and sensitivity-adjusted multivariate regression models for the 60-day and 6-month follow-up outcomes.

Supplementary Material 2. Organizational structure and process survey details

Background: This study assessed the contribution of organizational structures and processes identified from facility surveys to follow-up for positive fecal occult blood tests [FOBT-positive (FOBT+)].Methods: We identified 74,104 patients with FOBT+ results from 98 Veterans Health Administration (VHA) facilities between August 16, 2009 and March 20, 2011, and followed them until September 30, 2011, for completion of colonoscopy. We identified patient characteristics from VHA administrative records, and organizational factors from facility surveys completed by primary care and gastroenterology chiefs. We estimated predictors of colonoscopy completion within 60 days and six months using hierarchical logistic regression models.Results: Thirty percent of patients with FOBT+ results received colonoscopy within 60 days and 49% within six months. Having gastroenterology or laboratory staff notify gastroenterology providers directly about FOBT+ cases was a significant predictor of 60-day [odds ratio (OR), 1.85; P = 0.01] and six-month follow-up (OR, 1.25; P = 0.008). Additional predictors of 60-day follow-up included adequacy of colonoscopy appointment availability (OR, 1.43; P = 0.01) and frequent individual feedback to primary care providers about FOBT+ referral timeliness (OR, 1.79; P = 0.04). Additional predictors of six-month follow-up included using guideline-concordant surveillance intervals for low-risk adenomas (OR, 1.57; P = 0.01) and using group appointments and combined verbal–written methods for colonoscopy preparation instruction (OR, 1.48; P = 0.0001).Conclusion: Directly notifying gastroenterology providers about FOBT+ results, using guideline-concordant adenoma surveillance intervals, and using colonoscopy preparations instruction methods that provide both verbal and written information may increase overall follow-up rates. Enhancing follow-up within 60 days may require increased colonoscopy capacity and feedback to primary care providers.Impact: These findings may inform organizational-level interventions to improve FOBT+ follow-up. Cancer Epidemiol Biomarkers Prev; 24(2); 422–34. ©2014 AACR.

Supplementary Material 3. Codes used to identify colonoscopy procedures

Supplementary Material 4. Methods used to identify and adjust for reasons for not completing a colonoscopy.

Supplementary Material 1. Codes used to identify FOBT procedures

Supplementary Table 1. Bivariate odds ratios and follow-up percentage estimates used for model building

Rationale: Many patients with suspected chronic obstructive pulmonary disease (COPD) do not undergo spirometry to confirm the diagnosis. Underutilization is often attributed to barriers to accessing spirometry. Objective: Our objective wasto identify factors associated with spirometry underutilization for patients who are less likely to face access barriers related to travel, insurance, and availability of spirometry. Methods: A retrospective analysis was conducted of patients enrolled in the Veterans Health Administration and living in urban areas with a new diagnosis of COPD between 2012 to 2015, reducing out-of-pocket cost and travel barriers, respectively. We included only patients whose primary care clinic was located in an academically affiliated tertiary level facility with spirometry available. We used logistic regression to estimate associations between patient characteristics and receipt of spirometry within 2 years before or after COPD diagnosis. Results: Of 24,300 patients, 59.7% had spirometry. Compared to patients

Objective To assess whether change in HRQOL over a seven-year period was associated with subsequent mortality and hospitalization, after adjusting for important covariates, in a cohort of U.S. Veterans. Methods We used data from a cohort of Veterans who completed a HRQOL survey in 1998 (Short-Form 36 for Veterans [SF-36V]) and a 2006 follow-up (SF-12V) HRQOL survey and SF12V scores were calculated at both time-points. We used logistic regression analyses to model the relationship between changes in the SF12-V physical component (PCS) and mental health component (MCS) scores and 1-year hospitalization and 1-year and 3.3-year mortality after the 2006 follow-up survey. Results 13,900 participants provided data for both the initial and follow-up surveys. We found no significant associations between changes in PCS or MCS and one-year hospitalization after adjusting for follow-up HRQOL and other covariates. We found significant but relatively weak associations between changes in MCS and our mortality outcomes. Conclusion Given the follow-up MCS and PCS, change in PCS over the previous 7 years added little information for predicting mortality and hospitalization Although the change in MCS added some information for predicting mortality. Therefore, knowledge of patient's current HRQOL generally provides meaningful information for predicting subsequent mortality and hospitalization.

Sympathetic activation is a hallmark of pregnancy. However, longitudinal assessments of muscle sympathetic nerve activity (MSNA) in pregnancy are scarce and have primarily focused on burst occurrence (frequency) at rest, despite burst strength (amplitude) representing distinct characteristics of sympathetic outflow. Thus, we assessed MSNA burst amplitude distributions in healthy women to determine the impact of normal pregnancy on neural discharge patterns in response to orthostatic stress. Twenty-six women were studied longitudinally during pre-, early- (4–8 wk of gestation), and late (32–36 wk) pregnancy, as well as postpartum (6–10 wk after delivery). MSNA, blood pressure (BP), and heart rate (HR) were measured in the supine posture and during graded head-up tilt (30° and 60° HUT). Mean and median MSNA burst amplitudes were used to characterize burst amplitude distribution. In late pregnancy, women demonstrated smaller increases in HR ( P < 0.001) during 60° HUT and larger increases in systolic BP ( P = 0.043) throughout orthostasis, compared with prepregnancy. The increase in MSNA burst frequency during late- relative to prepregnancy (Late: Δ14[10] vs. Pre: Δ21[9] bursts/min; P = 0.001) was smaller during 60° HUT, whereas increases in burst incidence were smaller in late- relative to prepregnancy throughout orthostasis ( P = 0.009). Nonetheless, median burst amplitude was smaller throughout orthostasis in late compared with prepregnancy ( P = 0.038). Thus, while supine MSNA burst frequency was greater in late pregnancy, increases in burst frequency and strength during orthostasis were attenuated. These smaller, orthostatically induced MSNA increases may reflect natural adaptions of pregnancy serving to prevent sympathetic hyper-reactivity that is common in pathological states.

BACKGROUND Neonatal hypoglycemia may affect long-term neurodevelopment. METHODS Quality improvement (QI) initiative for Mother-Baby-Unit (MBU) admissions (birthweight ≥ 2100 g; ≥35 weeks' gestation) over two epochs from 2016-2019 to reduce the frequency of early (≤3 h) neonatal hypoglycemia in small and large newborns. INTERVENTION New algorithm using Olsen's growth curves, hypoglycemia thresholds of 3 to 24 h), feeding optimization and 24-hour glucose checks for small for gestational age and preterm newborns. RESULTS Among 39,460 newborns, using subsets with identical screening criteria, early hypoglycemia decreased significantly after QI implementation among large for gestational age newborns with birthweight >3850 g (66%) and small for gestational age newborns with birthweight

OBJECTIVES Our primary objective was to evaluate how prenatal diagnosis of a major fetal structural anomaly and resulting pregnancy outcome affected postpartum depression risk, as assessed by the Edinburgh Postnatal Depression Scale (EPDS). Secondary objectives were to review the rate of mental health follow-up and subsequent diagnosis of postpartum depression in screen-positive women. STUDY DESIGN Singleton pregnancies with prenatal diagnosis of one or more major fetal structural anomalies were ascertained from prospectively maintained databases that included perinatal outcomes and subsequent EPDS responses from January 2010 to May 2018. EPDS scores of 13 or higher were considered positive and prompted referral for mental health follow-up, which was verified by medical record review. Statistical analyses were performed using Student's t-test, χ2, and odds ratios (ORs) with p

ImportanceMany patients do not receive recommended services. Drive time to health care services may affect receipt of guideline-recommended care, but this has not been comprehensively studied.ObjectiveTo assess associations between drive time to care and receipt of guideline-recommended screening, diagnosis, and treatment interventions.Design, Setting, and ParticipantsThis cohort study used administrative data from the National Veterans Health Administration (VA) data merged with Medicare data. Eligible participants were patients using VA services between January 2016 and December 2019. Women ages 65 years or older without underlying bone disease were assessed for osteoporosis screening. Patients with new diagnosis of chronic obstructive pulmonary disease (COPD) indicated by at least 2 encounter codes for COPD or at least 1 COPD-related hospitalization were assessed for receipt of diagnostic spirometry. Patients hospitalized for ischemic heart disease were assessed for cardiac rehabilitation treatment.ExposuresDrive time from each patient’s residential address to the closest VA facility where the service was available, measured using geocoded addresses.Main Outcomes and MeasuresBinary outcome at the patient level for receipt of osteoporosis screening, spirometry, and cardiac rehabilitation. Multivariable logistic regression models were used to assess associations between drive time and receipt of services.ResultsOf 110 780 eligible women analyzed, 36 431 (32.9%) had osteoporosis screening (mean [SD] age, 66.7 [5.4] years; 19 422 [17.5%] Black, 63 403 [57.2%] White). Of 281 130 patients with new COPD diagnosis, 145 249 (51.7%) had spirometry (mean [SD] age, 68.2 [11.5] years; 268 999 [95.7%] men; 37 834 [13.5%] Black, 217 608 [77.4%] White). Of 73 146 patients hospitalized for ischemic heart disease, 11 171 (15.3%) had cardiac rehabilitation (mean [SD] age, 70.0 [10.8] years; 71 217 [97.4%] men; 15 213 [20.8%] Black, 52 144 [71.3%] White). The odds of receiving recommended services declined as drive times increased. Compared with patients with a drive time of 30 minutes or less, patients with a drive time of 61 to 90 minutes had lower odds of receiving osteoporosis screening (adjusted odds ratio [aOR], 0.90; 95% CI, 0.86-0.95) and spirometry (aOR, 0.90; 95% CI, 0.88-0.92) while patients with a drive time of 91 to 120 minutes had lower odds of receiving cardiac rehabilitation (aOR, 0.80; 95% CI, 0.74-0.87). Results were similar in analyses restricted to urban patients or patients whose primary care clinic was in a tertiary care center.Conclusions and RelevanceIn this retrospective cohort study, longer drive time was associated with less frequent receipt of guideline-recommended services across multiple components of care. To improve quality of care and health outcomes, health systems and clinicians should adopt strategies to mitigate travel burden, even for urban patients.

Objective The study aimed to evaluate the association between hemoglobin A1c values and likelihood of fetal anomalies in women with pregestational diabetes.Study Design Women with pregestational diabetes who delivered at a single institution that serves a nonreferred population from May 1, 2009 to December 31, 2018 were ascertained. Hemoglobin A1c values were obtained at the first prenatal visit. Women who delivered a singleton live- or stillborn infant with a major malformation as defined by European Surveillance of Congenital Anomalies criteria were identified. In infants with multiple system anomalies, each malformation was considered separately. Hemoglobin A1c values were analyzed categorically by using Mantel–Haenszel method and continuously with linear regression for trend for fetal anomalies.Results A total of 1,676 deliveries to women with pregestational diabetes were delivered at our institution, and hemoglobin A1c was assessed in 1,573 deliveries (94%). There were 129 deliveries of an infant with at least one major malformation, an overall anomaly rate of approximately 8%. Mean hemoglobin A1c concentration was significantly higher in pregnancies with anomalous infants, 9.3 ± 2.1% versus 8.0 ± 2.1%, and p Conclusion In women with pregestational diabetes, hemoglobin A1c is strongly associated with fetal anomaly risk. Data from a contemporary cohort may facilitate counseling and also highlight the need for preconceptual care and glycemic optimization prior to entry to obstetric care.Key Points

Objective Acute kidney injury (AKI)-complicating pregnancy is used as a marker of severe maternal morbidity (SMM) and frequently associated with obstetric hypertensive disorders. We examined AKI in pregnancies complicated by late-onset preeclampsia with severe features (SPE) using the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. We compared outcomes of pregnancies with and without AKI and stratified by stage of disease. We further differentiated renal dysfunction at the time of admission and compared outcomes to those who developed AKI after admission. Study Design This was a retrospective cohort study of women with care established before 20 weeks and diagnosed with preeclampsia with severe features with delivery at ≥34 weeks. Women with chronic hypertension or suspected underlying renal dysfunction were excluded. KDIGO criteria were applied to stratify staging of renal disease. Demographics and perinatal outcomes were compared using Chi-square analysis and Wilcoxon's rank-sum test with p Results From January 2015 through December 2019, a total of 3,515 women meeting study criteria were delivered. Of these, 517 (15%) women met KDIGO criteria for AKI at delivery with 248 (48%) having AKI at the time of admission and the remaining 269 (52%) after admission. Stratified by severity, 412 (80%) had stage 1 disease, 89 (17%) had stage II, and 16 (3%) had stage III. Women with AKI had higher rates of cesarean delivery (risk ratio [RR] = 1.3; 95% confidence interval [CI]: 1.17–1.44), postpartum hemorrhage (RR = 1.46; 95% CI: 1.29–1.66), and longer lengths of stay. Other associated outcomes included NICU admission (RR = 1.72; 95% CI: 1.19–2.48), 5-minute Apgar score ≤ 3 (RR = 5.11; 95% CI: 1.98–13.18), and infant length of stay. Conclusion Of women with late preterm SPE, 15% were found to have AKI by KDIGO criteria. The majority (80%) of AKI was stage I disease, and approximately half of the cases were present by the time of admission. Key Points

The present study examined whether certain Veterans Health Administration (VHA) therapists have more success than others in keeping patients engaged in evidence-based psychotherapies for posttraumatic stress disorder (PTSD). Our objective was to use multilevel modeling to quantify the variability between therapists in two indicators of patient engagement: early dropout (i.e., < 3 sessions) and adequate dose (i.e., ≥ 8 sessions). The phenomenon of systematic variability between therapists in patients' treatment experience and outcomes is referred to as "therapist effects." The sample included the 2,709 therapists who provided individual cognitive processing therapy (CPT) or prolonged exposure (PE) to 18,461 veterans with PTSD across 140 facilities in 2017. Data were extracted from administrative databases. For CPT, therapist effects accounted for 10.9% of the variance in early dropout and 8.9% of the variance in adequate dose. For PE, therapist effects accounted for 6.0% and 8.8% of the variance in early dropout and adequate dose, respectively. Facility only accounted for an additional 1.1%-3.1% of the variance in early dropout and adequate dose. For CPT, patients' odds of receiving an adequate dose almost doubled, OR = 1.41/0.72 = 1.96, if they were seen by a therapist in the highest compared with the lowest retention decile. For PE, the odds of a patient receiving an adequate dose were 84% higher, OR = 1.38/0.75 = 1.84, when treated by a therapist in the highest compared with the lowest retention decile. Therapist skills and work environment may contribute to variability across therapists in early dropout and adequate dose.

Although substantial efforts have been made to reduce rates of adolescent pregnancy, the United States continues to have higher rates than other industrialized countries. Research and reporting usually focus on adolescents 15 to 19 years of age. While less common, there are pregnant young adolescents that are 15 years of age and younger, with developmental and social differences from older, high school aged adolescents.Because adolescent pregnancies are of particular concern due to long-term socioeconomic consequences to parent and child, we sought to determine whether young adolescents (≤15 years old) had worse perinatal outcomes than older adolescents (16-19 years old) and older parents (≥20-34 years old) among those living in an urban inner-city.This was a study of pregnant individuals who delivered a singleton gestation without evidence of chronic hypertension or pregestational diabetes at a safety net hospital from January 2010 to May 2021. Parents were grouped by age at time of delivery into young adolescents (≤15 years old) and older adolescents (16-19 years old). For a comparison group, nulliparous older parents aged 20-34 years old with singleton pregnancies were analyzed for perinatal outcomes and compared to the adolescent cohorts. When analyzing baseline parental characteristics, a preponderance of obesity was noted in the young adolescent cohort. An analysis of parental characteristics and perinatal outcomes among obese versus non-obese young adolescents ≤15 years old was performed. Statistical analysis included χ2 and Student-t test with P values.05 considered significant. Logistic regression analysis was performed to control for potential confounding demographic variables.A total of 10,894 adolescent women delivered with 868 young adolescents and 10,026 older adolescents. Pairwise comparisons showed young adolescents had a different race distribution than older adolescents (P=0.006) and older parents (P0.001). Young adolescents were more likely to be Hispanic or non-Hispanic Black (P0.001) and accessed prenatal care at a later gestational age (19.7 ±8.9 weeks) compared to older adolescents (16.7±8.6 weeks), and the comparison older cohort of parents(15.7±8.7 weeks) (P0.001) and less frequently in pregnancy (P0.001) compared to older parents. Young adolescents were more likely to have preterm birth37w (0.001) and eclampsia (0.5% vs 0.1%) (P=0.01) than older adolescents. As a result, low birth weights ≤2500g (P=0.02) and neonatal intensive care admission (P=0.048) were also increased in adolescents. When adjusted for race, ethnicity, and body mass index, preeclampsia with severe features (P0.001) and preterm birth37w (P=0.048) remained significant. Obese young adolescents compared to non-obese adolescents were more likely to have preeclampsia with severe features (OR=1.81 (95% CI: 1.22, 2.68)) and be delivered via cesarean delivery (OR=2.71 (95% CI: 1.85, 3.99)).In an urban inner-city, young adolescent parents were more likely to be women of color, have later presentations to prenatal care, and have increased rates of preterm birth. Young adolescents had high rates of obesity which was associated with increased rates of hypertensive disorders of pregnancy and cesarean delivery compared to non-obese adolescents.

Enhanced recovery after surgery protocols are known to accelerate immediate postoperative recovery and to facilitate healing. Our purpose was to further characterize benefits after discharge from the hospital.An institutional database was queried to identify patients with clinical stage I non-small cell lung cancer who were classified as Eastern Cooperative Oncology Group performance status 0 and received a lobectomy between January 1, 2000, and August 31, 2020. The presence or absence of symptoms (ie, pain, shortness of breath, fatigue, among others) and performance status were recorded by clinic staff at the time of follow-up. Cox proportional hazards regression was used to identify factors associated with postdischarge recovery, which was defined as a return to Eastern Cooperative Oncology Group performance status 0 in the follow-up clinic.A total of 935 patients were identified (pre-enhanced recovery after surgery, 523; transition period, 222; enhanced recovery after surgery, 190). Outpatient performance status data were recorded in 774 of 935 patients (83%). The number of patients reporting symptoms at the 1-month follow-up appointment decreased from the pre-enhanced recovery after surgery to transition to the enhanced recovery after surgery period (60%, 50%, and 33%, respectively, P .001), predominately due to less pain reported (43%, 35%, and 23%, respectively, P = .001). At 6-month follow-up, these differences were no longer statistically significant. Surgery during the enhanced recovery after surgery period was independently associated with significant improvements in postdischarge recovery (hazard ratio, 1.60, 95% confidence interval, 1.29-2.00), and the presence of coronary artery disease (hazard ratio, 0.69, P = .006) and receipt of thoracotomy (hazard ratio, 0.84, P = .036) were independently associated with delayed postdischarge recovery.Enhanced recovery is associated with significant improvements in postdischarge recovery of performance status.

The first goal of this study was to assess longitudinal changes in burnout among psychotherapists prior to (T1) and during the COVID-19 pandemic (T2). The second objective was to assess the effects of job demands, job resources (including organizational support for evidence-based psychotherapies, or EBPs) and pandemic-related stress (T2 only) on burnout.Psychotherapists providing EBPs for posttraumatic stress disorder in U.S. Department of Veterans Affairs (VA) facilities completed surveys assessing burnout, job resources, and job demands prior to (T1; n = 346) and during (T2; n = 193) the COVID-19 pandemic.Burnout prevalence increased from 40 % at T1 to 56 % at T2 (p .001). At T1, stronger implementation climate and implementation leadership (p .001) and provision of only cognitive processing therapy (rather than use of prolonged exposure therapy or both treatments; p .05) reduced burnout risk. Risk factors for burnout at T2 included T1 burnout, pandemic-related stress, less control over when and how to deliver EBPs, being female, and being a psychologist rather than social worker (p .02). Implementation leadership did not reduce risk of burnout at T2.This study involved staff not directly involved in treating COVID-19, in a healthcare system poised to transition to telehealth delivery.Organizational support for using EBPs reduced burnout risk prior to but not during the pandemic. Pandemic related stress rather than increased work demands contributed to elevated burnout during the pandemic. A comprehensive approach to reducing burnout must address the effects of both work demands and personal stressors.

Severe hypertension remains one of the leading preventable causes of maternal mortality in the United States. Timeliness to response to severe hypertension in pregnancy is a crucial quality indicator tracked by state and national organizations. We hypothesized that the implementation of the Maternal-Fetal Triage Index, a validated acuity tool, would improve care performance in women with severe hypertension in an urban, inner-city hospital setting.This study aimed to assess the impact of the Maternal-Fetal Triage Index on the management of women presenting with severe preeclampsia diagnosed by severe hypertension as measured by time to provider assessment, administration of magnesium sulfate, and immediate administration of acute antihypertensives.This was a prospective, observational study of pregnant women presenting to the labor and delivery triage unit with severe preeclampsia diagnosed by severe hypertension giving birth at a large urban inner-city academic facility before (epoch 1: January 1, 2019, to December 31, 2019) and after (epoch 2: March 1, 2021, to September 31, 2021) the implementation of the Maternal-Fetal Triage Index. Baseline outcomes of time to assessment, time to magnesium sulfate prophylaxis, and time to antihypertensive medication administration before the implementation of the Maternal-Fetal Triage Index were assessed. The Maternal-Fetal Triage Index tool was implemented on March 1, 2021, following standardized education in 2020 for all triage nurses, unit technicians, healthcare unit coordinators, and healthcare providers. Time to assessment, administration of magnesium sulfate prophylaxis, and time to antihypertensive administration after the implementation of the Maternal-Fetal Triage Index were compared with measures before the implementation of the Maternal-Fetal Triage Index. Statistical analysis included Wilcoxon rank-sum test with P.05 considered significant when comparing epoch 1 with epoch 2.A total of 370 patients were admitted with severe hypertension in 2019 before the use of the Maternal-Fetal Triage Index, and 254 patients were admitted with severe hypertension in 2021 after the implementation of the Maternal-Fetal Triage Index. There was no difference between epochs across baseline characteristics, including age, race and ethnicity, parity, and body mass index. After the Maternal-Fetal Triage Index was implemented, the time to provider assessment was significantly improved, from a median time of 44 minutes (interquartile range, 0-65) in epoch 1 to 17 minutes (interquartile range, 0-39) in epoch 2 (P.001). Furthermore, the time from arrival to magnesium sulfate prophylaxis was significantly faster with a median time of 161 minutes (interquartile range, 109-256) in epoch 1 vs 127 minutes (interquartile range, 85-258) in epoch 2 (P=.001). Moreover, there was a decrease in the time from arrival to antihypertensive medication administration for severe blood pressures after the implementation of the Maternal-Fetal Triage Index (101 minutes [interquartile range, 61-177] vs 66 minutes [interquartile range, 35-203]; P.001).The implementation of the Maternal-Fetal Triage Index at a large urban inner-city hospital was associated with improved timeliness of assessment and treatment of women with severe hypertension. The Maternal-Fetal Triage Index is a viable tool to improve the efficiency in triage units, specifically in the management of severe hypertension.

Objective To evaluate whether the induction of labor in term gravid women with cervical dilation 2 cm or less and intact membranes by using oral misoprostol preceded by transcervical Foley bulb placement results in a significantly increased vaginal delivery rate compared with the use of oral misoprostol alone. Methods We randomized the induction method by week of admission to labor and delivery, with each week group described as a cluster in a block randomized design. Women with gestational age of 37 weeks or greater, cervical dilation 2 cm or less, intact membranes, and indication for labor induction were included. Study arms were either 100 micrograms of oral misoprostol after transcervical Foley bulb placement or 100 micrograms of oral misoprostol alone. The primary outcome was vaginal delivery with the first induction attempt. Secondary outcomes included time to delivery, clinical chorioamnionitis (maternal temperature of 38°C or greater during labor with or without fundal tenderness, without other identified cause), cesarean delivery indication, and adverse outcomes. We estimated that a sample size of 1,077 per arm was needed to detect a 5% increase in vaginal delivery rate with a type I error of 5% and power of 80%, accounting for interim analysis and cluster size of 30 inductions per week. This was a pragmatic trial, and analysis was by intention-to-treat. Results From January 1, 2018, to May 13, 2019, 1,117 women (34 clusters) were assigned to oral misoprostol plus Foley and 1,110 women (34 clusters) to oral misoprostol alone. Demographic characteristics were similar. Vaginal delivery at the first induction occurred in 78% of the misoprostol plus Foley arm and in 77% of the misoprostol arm (relative risk [RR] 1.00; 95% CI 0.96-1.05; adjusted relative risk [aRR], 1.00; 95% CI 0.95-1.05). Clinical chorioamnionitis occurred in 18% of the misoprostol plus Foley arm and in 14% of the misoprostol arm (RR 1.30; 95% CI 1.07-1.58; aRR 1.30; 95% CI 1.08-1.56). There were no differences in neonatal outcomes. Conclusion Induction of labor in gravid women at term with intact membranes by using oral misoprostol plus Foley bulb did not result in a higher vaginal delivery rate, but it did result in more clinical chorioamnionitis compared with the use of oral misoprostol alone. Clinical trial registration ClinicalTrials.gov, NCT03407625.

BACKGROUND: Mutations in the serine-threonine kinase LKB1/STK11 have been implicated in mediating resistance to checkpoint blockade among patients with advanced lung adenocarcinoma. We sought to examine the associations between clinicopathologic characteristics, tumor LKB1 expression, features of the immune microenvironment, and postoperative prognosis among patients with early-stage lung adenocarcinoma undergoing surgical therapy. METHODS: Formalin-fixed, paraffin-embedded specimens of patients undergoing resection of stage I-III, chemotherapy-naïve adenocarcinomas (1997–2008) were analyzed using tissue microarray sectioning. Sublobar resections were excluded. Intratumoral LKB1/STK11 expression was quantified as H-score. In a subset, tumor associated immune cell populations were quantified using whole tumor sections in peritumoral and intratumoral compartments. RESULTS: 104 patients met inclusion criteria. LKB1/STK11 expression (median H-score 102.9) was higher in women (median 123.3) than men (100.0, p=0.004) and in never-smokers (median 145.0) than former/current smokers (100.0, p=0.002). LKB1/STK11 expression was positively correlated with intratumoral infiltration of CD3(+) (r=0.351, P=0.005), CD4(+) (r=0.436, P

Background and aims Acute liver failure (ALF), characterized by sudden onset of coagulopathy (international normalized ratio [INR] ≥ 1.5) and encephalopathy, may occur during pregnancy either as a pregnancy-associated etiology or an unrelated and coincidental liver injury. The U.S. Acute Liver Failure Study Group, comprised of 33 tertiary care liver centers, has enrolled consecutive patients with ALF or acute liver injury (ALI; INR ≥ 2.0 with no encephalopathy), over two decades. Approach and results Etiologies, clinical features, and outcomes of 70 of 3,155 patients (2.2%) who developed ALF or ALI during pregnancy were reviewed to determine how many were pregnancy associated (pregnancy-associated liver disease; PAALD) and how many were attributed to other etiologies. Thirty-five of the 70 were considered PAALD, of whom nearly half were attributed to hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome and half to acute fatty liver of pregnancy (AFLP), although, in some instances, the distinction was unclear. Virtually all with PAALD had been delivered before hepatology referral, mostly by cesarean section. Acetaminophen toxicity accounted for 21 (60% of the remaining cases), with the remainder resulting from a variety of other causes, but not including viral hepatitis A through E. Although recovery with delivery or supportive measures was possible in most cases, 11 of 70 (16%) required liver transplantation and 8 (11%) died. Swansea criteria to diagnose AFLP were met by all patients with PAALD and also by virtually all women with other forms of ALF. Conclusions Only half of those with ALF during pregnancy appeared to have HELLP or AFLP. Morbidity and mortality for mother and fetus are strongly associated with etiology of liver failure.

Objective Although intrahepatic cholestasis of pregnancy (ICP) remains poorly understood, there are several perinatal complications associated with this condition. This study aimed to examine perinatal outcomes of women with ICP, evaluate outcomes according to severity of disease, and monitor time to symptom improvement following diagnosis. Study Design It involves a prospective, observational study of women with ICP at a single institution. Women with new-onset pruritus without rash were referred to a high-risk obstetrics clinic and evaluated with fasting total bile acids (TBA). Laboratory-confirmed ICP was defined as fasting TBA ≥10 µmol/L. Following diagnosis, a standardized protocol was utilized, including treatment with ursodeoxycholic acid (UDCA). Perinatal outcomes were compared amongst those with and without ICP, and to the general population. Women with ICP were further analyzed based on maximum TBA: 10 to 39, 40 to 99, and ≥100 µmol/L. A Kaplan-Meier survival curve was used to analyze time to symptom improvement. Results A total of 404 patients were evaluated and 212 (52%) were diagnosed with ICP. The mean gestational age at diagnosis was 34.1 ± 3.3 weeks. When comparing those with ICP to those not confirmed, and to the general population, there were no differences in age, parity, mode of delivery, preeclampsia, or stillbirth (p > 0.05). Preterm birth was significantly associated with ICP (p Conclusion Despite treatment with UDCA, women with ICP are at increased risk for spontaneous preterm birth, and this risk significantly increased with severity of disease. Although not significant, a trend exists between increasing time to symptom improvement and worsening severity of disease. Key Points

Acute fatty liver of pregnancy (AFLP) and hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome are both associated with significant maternal and perinatal morbidity and mortality. Because of the overlap of several clinical and laboratory findings differentiation can sometimes be difficult. Both disorders have been of interest for more than 100 years, however they were not completely characterized until the early 1980s. It was not until the 1980s that AFLP and HELLP syndrome, and more specifically their clinical, laboratory, and pathologic findings, were further differentiated in the literature. More recently, the pathophysiologic mechanisms have been elucidated. In this review, we outline the similarities and differences in the clinical presentation, laboratory findings, maternal and perinatal outcomes, and clinical recovery for women diagnosed with these two syndromes. From our observations, we suggest that levels of fibrinogen, creatinine, cholesterol, and total bilirubin be used to assist with differentiating AFLP from HELLP syndrome upon admission in women presenting with either suspected disease. The rationale for identifying the specific conditions is that clinical consequences for recovery vary considerably. Specifically, AFLP is associated with significantly more hepatic and renal dysfunction as well as coagulopathy. Fortunately, both conditions can be managed with supportive measures with overall improved perinatal outcomes including morbidity and mortality.