Objective The objective of the Sleep Disordered Breathing substudy of the Nulliparous Pregnancy Outcomes Study Monitoring Mothers-to-be (nuMoM2b) is to determine whether sleep disordered breathing ...during pregnancy is a risk factor for adverse pregnancy outcomes. Study Design NuMoM2b is a prospective cohort study of 10,037 nulliparous women with singleton gestations that was conducted across 8 sites with a central Data Coordinating and Analysis Center. The Sleep Disordered Breathing substudy recruited 3702 women from the cohort to undergo objective, overnight in-home assessments of sleep disordered breathing. A standardized level 3 home sleep test was performed between 60 -150 weeks’ gestation (visit 1) and again between 220 -310 weeks’ gestation (visit 3). Scoring of tests was conducted by a central Sleep Reading Center. Participants and their health care providers were notified if test results met “urgent referral” criteria that were based on threshold levels of apnea hypopnea indices, oxygen saturation levels, or electrocardiogram abnormalities but were not notified of test results otherwise. The primary pregnancy outcomes to be analyzed in relation to maternal sleep disordered breathing are preeclampsia, gestational hypertension, gestational diabetes mellitus, fetal growth restriction, and preterm birth. Results Objective data were obtained at visit 1 on 3261 women, which was 88.1% of the studies that were attempted and at visit 3 on 2511 women, which was 87.6% of the studies that were attempted. Basic characteristics of the substudy cohort are reported in this methods article. Conclusion The substudy was designed to address important questions regarding the relationship of sleep-disordered breathing on the risk of preeclampsia and other outcomes of relevance to maternal and child health.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Abstract Background Experimental and epidemiologic data suggest that among non-pregnant adults, sleep duration may be an important risk factor for chronic disease. Although pregnant women commonly ...complain of poor sleep, few studies have objectively evaluated the quality of sleep in pregnancy or have explored the relationship between sleep disturbances and maternal and perinatal outcomes. Objectives Our objective was to examine the relationship between objectively assessed sleep duration, timing and continuity (measured via wrist actigraphy) and maternal cardiovascular and metabolic morbidity specific to pregnancy. Study Design This was a prospective cohort study of nulliparous women. Women were recruited between 16 0/7 and 21 6/7 weeks’ gestation. They were asked to wear a wrist actigraphy monitor and to complete a daily sleep log for a seven consecutive-day period. The primary sleep exposure variables were the averages of the following over the total valid nights (minimum 5, maximum 7 nights): short sleep duration during the primary sleep period (< 7 hours/night), late sleep midpoint (midpoint between sleep onset and sleep offset > 5 AM), and top quartile of minutes of wake time after sleep onset (WASO) and sleep fragmentation index. The primary outcomes of interest were a composite of hypertensive disorders of pregnancy (mild, severe, or superimposed preeclampsia; eclampsia; or antepartum gestational hypertension) and gestational diabetes (GDM). Chi-square tests were used to assess associations between sleep variables and categorical baseline characteristics. Crude odds ratios and 95% confidence intervals were estimated from univariate logistic regression models to characterize the magnitude of the relationship between sleep characteristics and hypertensive disorders of pregnancy and GDM. For associations that were significant in univariate analysis, multiple logistic regression was used to explore further the association of sleep characteristics with pregnancy outcomes. Results Nine-hundred and one eligible women consented to participate. Of these women 782 submitted valid actigraphy studies. Short sleep duration and a later sleep midpoint were associated with an increased risk of GDM (OR 2.24, 95% CI 1.11, 4.53; OR 2.58, 95% CI 1.24, 5.36, respectively) but not of hypertensive disorders. A model with both sleep duration and sleep midpoint as well as their interaction term revealed that while there was no significant interaction between these exposures, the main effects of both short sleep duration and later sleep midpoint with GDM remained significant (aOR 2.06, 95% CI 1.01, 4.19; aOR 2.37, 95% CI 1.13, 4.97, respectively). Additionally, after adjusting separately for age, BMI and race/ethnicity, both short sleep duration and later sleep midpoint remained associated with GDM. No associations were demonstrated between the sleep quality measures (WASO, sleep fragmentation) and hypertensive disorders or GDM. Conclusions Our results demonstrate a relationship between short sleep duration and later sleep midpoint with GDM. Our data suggest independent contributions of these two sleep characteristics to the risk for GDM in nulliparous women.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Background Preeclampsia complicates approximately 3–5% of pregnancies and remains a major cause of maternal and neonatal morbidity and mortality. It shares pathogenic similarities with adult ...cardiovascular disease as well as many risk factors. Pravastatin, a hydrophilic, 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitor, has been shown in preclinical studies to reverse various pathophysiological pathways associated with preeclampsia, providing biological plausibility for its use for preeclampsia prevention. However, human trials are lacking. Objective As an initial step in evaluating the utility of pravastatin in preventing preeclampsia and after consultation with the US Food and Drug Administration, we undertook a pilot randomized controlled trial with the objective to determine pravastatin safety and pharmacokinetic parameters when used in pregnant women at high risk of preeclampsia. Study Design We conducted a pilot, multicenter, double-blind, placebo-controlled, randomized trial of women with singleton, nonanomalous pregnancies at high risk for preeclampsia. Women between 120/7 and 166/7 weeks’ gestation were assigned to daily pravastatin 10 mg or placebo orally until delivery. Primary outcomes were maternal-fetal safety and pharmacokinetic parameters of pravastatin during pregnancy. Secondary outcomes included rates of preeclampsia and preterm delivery, gestational age at delivery, birthweight, and maternal and cord blood lipid profile ( clinicaltrials.gov identifier NCT01717586 ). Results Ten women assigned to pravastatin and 10 to placebo completed the trial. There were no differences between the 2 groups in rates of study drug side effects, congenital anomalies, or other adverse or serious adverse events. There was no maternal, fetal, or neonatal death. Pravastatin renal clearance was significantly higher in pregnancy compared with postpartum. Four subjects in the placebo group developed preeclampsia compared with none in the pravastatin group. Although pravastatin reduced maternal cholesterol concentrations, umbilical cord cholesterol concentrations and infant birthweight were not different between the groups. The majority of umbilical cord and maternal pravastatin plasma concentrations at the time of delivery were below the lower limit of quantification of the assay. Pravastatin use was associated with a more favorable pregnancy angiogenic profile. Conclusion This study provides preliminary safety and pharmacokinetic data regarding the use of pravastatin for preventing preeclampsia in high-risk pregnant women. Although the data are preliminary, no identifiable safety risks were associated with pravastatin use in this cohort. This favorable risk-benefit analysis justifies using pravastatin in a larger clinical trial with dose escalation.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Objective The primary aim of the “Nulliparous Pregnancy Outcomes Study: monitoring mothers-to-be” is to determine maternal characteristics, which include genetic, physiologic response to pregnancy, ...and environmental factors that predict adverse pregnancy outcomes. Study Design Nulliparous women in the first trimester of pregnancy were recruited into an observational cohort study. Participants were seen at 3 study visits during pregnancy and again at delivery. We collected data from in-clinic interviews, take-home surveys, clinical measurements, ultrasound studies, and chart abstractions. Maternal biospecimens (serum, plasma, urine, cervicovaginal fluid) at antepartum study visits and delivery specimens (placenta, umbilical cord, cord blood) were collected, processed, and stored. The primary outcome of the study was defined as pregnancy ending at <37+0 weeks’ gestation. Key study hypotheses involve adverse pregnancy outcomes of spontaneous preterm birth, preeclampsia, and fetal growth restriction. Results We recruited 10,037 women to the study. Basic characteristics of the cohort at screening are reported. Conclusion The “Nulliparous Pregnancy Outcomes Study: monitoring mothers-to-be” cohort study methods and procedures can help investigators when they plan future projects.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Abstract Background Failure of physiologic transformation of spiral arteries has been reported in preeclampsia, fetal growth restriction, fetal death, and spontaneous preterm labor with intact or ...ruptured membranes. Spiral arteries with failure of physiologic transformation are prone to develop atherosclerotic-like lesions of atherosis. There are striking parallels between preeclampsia and atherosclerotic disease, and between lesions of atherosis and atherosclerosis. Endothelial activation, identified by intercellular adhesion molecule-1 (ICAM-1) expression, is present in atherosclerotic-like lesions of heart transplantation, and is considered a manifestation of rejection. Similarly, endothelial activation/dysfunction has been implicated in the pathophysiology of atherosclerosis and preeclampsia. ICAM-1-overexpressing activated endothelial cells are more resistant to trophoblast displacement than non-activated endothelium, and may contribute to shallow spiral artery trophoblastic invasion in obstetrical syndromes having failure of physiologic transformation. Objective To determine whether failure of spiral artery physiologic transformation was associated with activation of interstitial extravillous trophoblasts and/or spiral artery endothelium and presence of acute atherosis in the placental basal plate. Study Design A cross-sectional study of 123 placentas (19 to 42 weeks gestation) obtained from normal pregnancies (n = 22), preterm prelabor rupture of membranes (n = 26), preterm labor (n = 23), preeclampsia (n = 27), intrauterine fetal death (n = 15) and small for gestational age (n = 10), was performed. Failure of spiral artery physiologic transformation and presence of cell activation was determined using immunohistochemistry of placental basal plates containing a median of 4 (minimum: 1; maximum: 9) vessels per placenta. Endothelial/trophoblast cell activation was defined by the expression of ICAM-1. Investigators examining microscopic sections were blinded to clinical diagnosis. Pairwise comparisons among placenta groups were performed with Fisher's exact test and Wilcoxon rank sum test using a Bonferroni-adjusted level of significance (0.025). Results We found that 87% (94/108) of placentas having spiral arteries with failure of physiologic transformation ( actin-positive and cytokeratin-negative) in the basal plate, and 0% (0/15) of placentas having only spiral arteries with complete physiologic transformation ( cytokeratin-positive and actin-negative), had arterial endothelial and/or interstitial extravillous trophoblasts reactive with the ICAM-1 activation marker ( P < 0.001). A significant correlation (R2 = 0.84) was found between expression of spiral artery endothelial and interstitial extravillous trophoblast ICAM-1 ( P < 0.001) in activated placentas. Lesions of atherosis were found in 31.9% (30/94) of placentas with complete and/or partial failure of physiologic transformation of spiral arteries ICAM-1-positive, in none of the 14 placentas with failure of physiologic transformation ICAM-1-negative, and in none of the 15 placentas with complete spiral artery physiologic transformation without failure ( P = 0.001). All placentas (30/30, 100%) with atherosis were identified in placentas having concomitant spiral artery endothelial and interstitial extravillous trophoblast activation. Conclusion Failure of spiral artery physiologic transformation in the placental basal plate is associated with interstitial extravillous trophoblast and arterial endothelial activation along with increased frequency of spiral artery atherosis. These findings may be used to improve the characterization of different disorders of the placental bed such as in refining the existing tools for the early prediction of risk for preterm, preeclamptic and other abnormal pregnancies.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Since the publication of “A Compendium of Strategies to Prevent Healthcare-Associated Infections in Acute Care Hospitals” in 2008, prevention of healthcare-associated infections (HAIs) has become a ...national priority. Despite improvements, preventable HAIs continue to occur. The 2014 updates to the Compendium were created to provide acute care hospitals with up-to-date, practical, expert guidance to assist in prioritizing and implementing their HAI prevention efforts. They are the product of a highly collaborative effort led by the Society for Healthcare Epidemiology of America (SHEA), the Infectious Diseases Society of America (IDSA), the American Hospital Association (AHA), the Association for Professionals in Infection Control and Epidemiology (APIC), and The Joint Commission, with major contributions from representatives of a number of organizations and societies with content expertise, including the Centers for Disease Control and Prevention (CDC), the Institute for Healthcare Improvement (IHI), the Pediatric Infectious Diseases Society (PIDS), the Society for Critical Care Medicine (SCCM), the Society for Hospital Medicine (SHM), and the Surgical Infection Society (SIS).
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Objective Microbial invasion of the amniotic cavity (MIAC) is common in early preterm labor and is associated with maternal and neonatal infectious morbidity. MIAC is usually occult and is reliably ...detected only with amniocentesis. We sought to develop a noninvasive test to predict MIAC based on protein biomarkers in cervicovaginal fluid (CVF) in a cohort of women with preterm labor (phase 1) and to validate the test in an independent cohort (phase 2). Study Design This was a prospective study of women with preterm labor who had amniocentesis to screen for MIAC. MIAC was defined by positive culture and/or 16S ribosomal DNA results. Nine candidate CVF proteins were analyzed by enzyme-linked immunosorbent assay. Logistic regression was used to identify combinations of up to 3 proteins that could accurately classify the phase 1 cohort (N = 108) into those with or without MIAC. The best models, selected by area under the curve (AUC) of the receiver operating characteristic curve in phase 1, included various combinations of interleukin (IL)-6, chemokine (C-X-C motif) ligand 1 (CXCL1), alpha fetoprotein, and insulin-like growth factor binding protein-1. Model performance was then tested in the phase 2 cohort (N = 306). Results MIAC was present in 15% of cases in phase 1 and 9% in phase 2. A 3-marker CVF model using IL-6 plus CXCL1 plus insulin-like growth factor binding protein-1 had AUC 0.87 in phase 1 and 0.78 in phase 2. Two-marker models using IL-6 plus CXCL1 or alpha fetoprotein plus CXCL1 performed similarly in phase 2 (AUC 0.78 and 0.75, respectively), but were not superior to CVF IL-6 alone (AUC 0.80). A cutoff value of CVF IL-6 ≥463 pg/mL (which had 81% sensitivity in phase 1) predicted MIAC in phase 2 with sensitivity 79%, specificity 78%, positive predictive value 38%, and negative predictive value 97%. Conclusion High levels of IL-6 in CVF are strongly associated with MIAC. If developed into a bedside test or rapid laboratory assay, cervicovaginal IL-6 might be useful in selecting patients in whom the probability of MIAC is high enough to warrant amniocentesis or transfer to a higher level of care. Such a test might also guide selection of potential subjects for treatment trials.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
BACKGROUND: Enhanced Recovery After Surgery pathways provide evidence-based recommendations to optimize perioperative care. OBJECTIVE: This study aimed to holistically investigate the effect of ...implementing an Enhanced Recovery After Surgery pathway for all cesarean deliveries on postoperative pain experience. STUDY DESIGN: This was a prepost study comparing subjective and objective measures of postoperative pain before and after the implementation of an Enhanced Recovery After Surgery pathway for cesarean delivery. The Enhanced Recovery After Surgery pathway was developed by a multidisciplinary team and included preoperative, intraoperative, and postoperative components, with emphasis on preoperative preparation, hemodynamic optimization, early mobilization, and multimodal analgesia. All individuals undergoing cesarean delivery, whether scheduled, urgent, or emergent, were included. Demographic, delivery, and inpatient pain management data were obtained through medical record review. Of note, 2 weeks after discharge, patients were surveyed about their delivery experience, analgesic usage, and complications. The primary outcome was inpatient opioid use. RESULTS: The study included 128 individuals, 56 in the preimplementation cohort and 72 in the Enhanced Recovery After Surgery cohort. Baseline characteristics between the 2 groups were similar. The survey response rate was 73% (94/128). Opioid use in the first 48 hours postoperatively was significantly lower in the Enhanced Recovery After Surgery group than the preimplementation group (9.4 vs 21.4 morphine milligram equivalents 0–24 hours after delivery P<.001; 14.1 vs 25.4 morphine milligram equivalents 24–48 hours after delivery P<.001) with no increase in either average or maximum postoperative pain scores. Individuals in the Enhanced Recovery After Surgery group used fewer opioid pills after discharge (10 vs 20; P<.001). Patient satisfaction and complication rates did not change after the implementation of an Enhanced Recovery After Surgery pathway. CONCLUSION: The implementation of an Enhanced Recovery After Surgery pathway for all cesarean deliveries decreased both inpatient and outpatient postpartum opioid use without increasing pain scores or decreasing patient satisfaction.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The availability of targeted therapies has transformed the management of advanced NSCLC; however, most patients do not undergo guideline-recommended tumor genotyping. The impact of plasma-based ...next-generation sequencing (NGS) performed simultaneously with diagnostic biopsy in suspected advanced NSCLC has largely been unexplored.
We performed a prospective cohort study of patients with suspected advanced lung cancer on the basis of cross-sectional imaging results. Blood from the time of biopsy was sequenced using a commercially available 74-gene panel. The primary outcome measure was time to first-line systemic treatment compared with a retrospective cohort of consecutive patients with advanced NSCLC with reflex tissue NGS.
We analyzed the NGS results from 110 patients with newly diagnosed advanced NSCLC: cohorts 1 and 2 included 55 patients each and were well balanced regarding baseline demographics. In cohort 1, plasma NGS identified therapeutically informative driver mutations in 32 patients (58%) (13 KRAS five KRAS G12C, 13 EGFR, two ERRB2, two MET, one BRAF, one RET). The NGS results were available before the first oncology visit in 85% of cohort 1 versus 9% in cohort 2 (p < 0.0001), with more cohort 1 patients receiving a guideline-concordant treatment recommendation at this visit (74% versus 46%, p = 0.005). Time-to-treatment was significantly shorter in cohort 1 compared with cohort 2 (12 versus 20 d, p = 0.003), with a shorter time-to-treatment in patients with specific driver mutations (10 versus 19 d, p = 0.001).
Plasma-based NGS performed at the time of diagnostic biopsy in patients with suspected advanced NSCLC is associated with decreased time-to-treatment compared with usual care.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Abstract Landmark early work has led to the nearly universal use of antenatal corticosteroids to accelerate fetal lung maturity with pregnancies complicated by impending preterm birth. Antenatal ...corticosteroids clearly reduce respiratory morbidity, death, and other adverse neonatal outcomes. Limited pregnant human pharmacokinetic data and some animal data give clinicians some information as to the behavior of the drug in the body. However, there is controversy about the type, amount, and frequency of steroid to use for this therapy. This review article summarizes the history, clinical use, and pharmacology of antenatal steroids. In addition, the review highlights some potential mediators of steroid response and current research strategies aimed at possible optimization of this therapy.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
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