Socioeconomic, Racial, and Ethnic Disparities in Postpartum Readmissions in Patients with Preeclampsia: a Multi-state Analysis, 2007-2014.

PURPOSE: Childbirth is the most common reason for hospitalization for reproductive-aged women, with about 4 million annual deliveries nationally. Hypertension is the leading indication for postpartum readmission and therefore women with preeclampsia are at high risk for readmission. Social determinants of health are associated with increased readmission in postpartum patients; however, no study has specifically investigated readmissions in this higher risk group of patients. We sought to evaluate the effect of social determinants of health on postpartum readmissions in all postpartum patients and in a subgroup analysis of those with a diagnosis of preeclampsia. METHODS: We conducted a retrospective (2007-2014) analysis of all singleton deliveries in Florida, California, New York, and Maryland from the State Inpatient Databases, Healthcare Cost and Utilization Project. Primary outcomes were readmission at 30 days after delivery. Descriptive statistics were calculated, and multivariate regression analysis was used to estimate the adjusted odds ratio (OR) for readmissions. Subgroup analysis was performed on preeclampsia patients only. Statistical significance was evaluated at the < 0.05 alpha level. RESULTS: A total of 4,999,993 patients were included in our analysis. Among all postpartum patients and in subgroup analysis for preeclampsia patients only, readmission rates are higher for black patients, patients in the poorest quartile of median income, and patients with public insurance (Medicare or Medicaid). CONCLUSIONS: The present study has shown that socioeconomic and racial/ethnic disparities exist in postpartum readmissions. These findings additionally exist among the already highest-risk preeclamptic patients. Future research should further elucidate this relationship and develop amelioration strategies.

Racial and Ethnic Disparities in Maternal Outcomes and the Disadvantage of Peripartum Black Women: A Multistate Analysis, 2007-2014.

OBJECTIVE: Racial and ethnic disparities in obstetric care and delivery outcomes have shown that black women experience high rates of pregnancy-related mortality and morbidity, along with high rates of cesarean delivery, compared with other racial and ethnic groups. We aimed to quantify these disparities and test the effects of race/ethnicity in stratified statistical models by insurance payer and socioeconomic status, adjusting for comorbidities specific to an obstetric population. STUDY DESIGN: We analyzed maternal outcomes in a sample of 6,872,588 delivery records from California, Florida, Kentucky, Maryland, and New York from 2007 to 2014 from the State Inpatient Databases, Healthcare Cost and Utilization Project. We compared present-on-admission characteristics of parturients by race/ethnicity, and estimated logistic regression and generalized linear models to assess outcomes of in-hospital mortality, cesarean delivery, and length of stay. RESULTS: Compared with white women, black women were more likely to die in-hospital (odds ratio [OR]: 1.90, 95% confidence interval [CI]: 1.47-2.45) and have a longer average length of stay (incidence rate ratio: 1.10, 95% CI: 1.09-1.10). Black women also were more likely to have a cesarean delivery (OR: 1.12, 95% CI 1.12-1.13) than white women. These results largely held in stratified analyses. CONCLUSION: In most insurance payers and socioeconomic strata, race/ethnicity alone is a factor that predicts parturient outcomes.

Massive pulmonary embolism in pregnancy treated with catheter-directed tissue plasminogen activator.

Pulmonary embolism is a leading cause of maternal death in the United States, contributing to the death of approximately 2 women per 100,000 live births each year. Thrombosis during pregnancy traditionally is treated conservatively with unfractionated heparin or low-molecular-weight heparin; however, cardiovascular collapse associated with a large pulmonary embolus may require immediate aggressive intervention to save the mother and fetus. We report the use of catheter infusion thrombolysis in the successful management of a third-trimester pregnant patient with a hemodynamically significant saddle pulmonary embolus.

Rapid eye movement sleep debt accrues in mice exposed to volatile anesthetics.

BACKGROUND: General anesthesia has been likened to a state in which anesthetized subjects are locked out of access to both rapid eye movement (REM) sleep and wakefulness. Were this true for all anesthetics, a significant REM rebound after anesthetic exposure might be expected. However, for the intravenous anesthetic propofol, studies demonstrate that no sleep debt accrues. Moreover, preexisting sleep debts dissipate during propofol anesthesia. To determine whether these effects are specific to propofol or are typical of volatile anesthetics, the authors tested the hypothesis that REM sleep debt would accrue in rodents anesthetized with volatile anesthetics. METHODS: Electroencephalographic and electromyographic electrodes were implanted in 10 mice. After 9-11 days of recovery and habituation to a 12 h:12 h light-dark cycle, baseline states of wakefulness, nonrapid eye movement sleep, and REM sleep were recorded in mice exposed to 6 h of an oxygen control and on separate days to 6 h of isoflurane, sevoflurane, or halothane in oxygen. All exposures were conducted at the onset of light. RESULTS: Mice in all three anesthetized groups exhibited a significant doubling of REM sleep during the first 6 h of the dark phase of the circadian schedule, whereas only mice exposed to halothane displayed a significant increase in nonrapid eye movement sleep that peaked at 152% of baseline. CONCLUSION: REM sleep rebound after exposure to volatile anesthetics suggests that these volatile anesthetics do not fully substitute for natural sleep. This result contrasts with the published actions of propofol for which no REM sleep rebound occurred.

Modulation of endothelial targeting by size of antibody-antioxidant enzyme conjugates.

Endothelial targeting of antioxidant enzymes attenuates acute vascular oxidative stress in animal studies. Superoxide dismutase (SOD) and catalase conjugated with antibodies to Platelet-Endothelial Cell Adhesion Molecule-1 (anti-PECAM/SOD and anti-PECAM/catalase) bind to endothelium, accumulate in the pulmonary vasculature, and detoxify reactive oxygen species. In order to define the role of conjugate size in the efficacy and specificity of endothelial targeting, we synthesized anti-PECAM/enzyme conjugates of controlled size (40nm-10,000nm). Binding of anti-PECAM/enzymes to endothelial cells increased with conjugate size from 300nm to 2µm (from 2.5 to 8.5% of bound fraction), and was specific, as conjugates did not bind to PECAM-negative cells. Pulmonary uptake of anti-PECAM/enzyme conjugates injected intravenously in mice also increased from 4.5 to 16% of injected dose for particles from 200 to 800nm. However, control conjugates larger than 300nm showed elevated non-specific pulmonary uptake, indicating that the targeting specificity of anti-PECAM/enzyme conjugates in vivo has a bell-shaped curve with a maximum close to 300-nm diameter. These results show that: i) the size of an antibody/enzyme conjugate modulates efficacy and specificity of targeting, and ii) a size optimum should be defined in vivo to account for parameters that are difficult to model in cell culture.

Factors modulating the delivery and effect of enzymatic cargo conjugated with antibodies targeted to the pulmonary endothelium.

Vascular drug targeting may improve therapies, yet a thorough understanding of the factors that regulate effects of drugs directed to the endothelium is needed to translate this approach into the clinical domain. To define factors modulating the efficacy and effects of endothelial targeting, we used a model enzyme (glucose oxidase, GOX) coupled with monoclonal antibodies (anti-TM(34) or anti-TM(201)) to distinct epitopes of thrombomodulin, a surface determinant enriched in the pulmonary endothelium. GOX delivery results in conversion of glucose and oxygen into H(2)O(2) leading to lung damage, a clear physiologic endpoint. Results of in vivo studies in mice showed that the efficiency of cargo delivery and its effect are influenced by a number of factors including: 1) The level of pulmonary uptake of the targeting antibody (anti-TM(201) was more efficient than anti-TM(34)); 2) The amount of an active drug delivered to the target; 3) The amount of target antigen on the endothelium (animals with suppressed TM levels showed less targeting); and, 4) The substrate availability for the enzyme cargo in the target tissue (hyperoxia augmented GOX-induced injury). Therefore, both activities of the conjugates and biological factors control targeting and effects of enzymatic cargo. Understanding the nature of such "modulating biological factors" will hopefully allow optimization and ultimately applications of drug targeting for "individualized" pharmacotherapy.

KL4-surfactant prevents hyperoxic and LPS-induced lung injury in mice.

KL(4)-surfactant contains the novel KL(4) peptide, sinapultide, which mimics properties of the hydrophobic pulmonary surfactant protein SP-B, in a phospholipid formulation and may be lung protective in experimental acute respiratory distress syndrome/acute lung injury. Our objective was to determine the protective role of airway delivery of KL(4)-surfactant in murine models of hyperoxic and lipopolysaccharide (LPS)-induced lung injury and further explore the mechanisms of protection. For the hyperoxic injury model, mice exposed to 80% O(2) for 6 days received an intranasal bolus of vehicle, beractant, or KL(4)-surfactant on days 3, 4, 5, and 6 of the exposure, and lungs were evaluated on day 7. Mice in the LPS-induced lung injury model received an intratracheal bolus of LPS followed by an intranasal bolus of KL(4)-surfactant or control at 1, 3, and 19 hr post-LPS challenge, and lungs were evaluated after 24 hr. To explore the mechanisms of protection, in vitro assays were performed with human and murine endothelial cell monolayers, and polymorphonuclear leukocyte (PMN) transmigration in the presence or absence of KL(4)-surfactant or lipid controls was evaluated. Based on morphology, histopathology, white blood cell count, percentage of PMNs, and protein concentration in bronchoalveolar lavage fluid, our data showed KL(4)-surfactant, unlike vehicle or beractant, blocked neutrophil influx into alveoli and suppressed lung injury. Furthermore, in vitro assays showed KL(4)-surfactant decreased neutrophil transmigration at the endothelial cell level. KL(4)-surfactant decreased inflammation and lung permeability compared with controls in both mouse models of lung injury. Evidence suggests the anti-inflammatory mechanism of the KL(4)-peptide is through inhibition of PMN transmigration through the endothelium.