Optimizing Post-Cesarean Opioid Prescription Practices at Mayo Clinic: A Quality Improvement Initiative.

OBJECTIVE: Optimal prescriptions practices of opioids in the post-cesarean period remain controversial. The primary aim of this initiative was to minimize unused prescription narcotic medication, with a goal of ≤4 leftover pills of 5-mg oxycodone at postoperative day (POD) 14 without affecting pain or satisfaction measures. STUDY DESIGN: This was a prospective longitudinal quality improvement (QI) initiative starting in 2017 utilizing the DMAIC methodology. The measurement phase consisted of validated surveys over 3 months, along with chart review to determine current institutional prescription practices and predictors of outpatient opioid use. Resulting recommendations were adopted, and 1 year later, all patients undergoing cesarean were surveyed for 3 months to determine the effectiveness of the intervention. The study was approved by the Department's QI Committee. RESULTS: The response rate was 48%, with 50 of 101 patients completing surveys pre-intervention and 52 of 111 post-intervention. Pre-intervention, surplus medication was predicted (p <0.05) only by the quantity of the opioid prescription. In addition, patients who required ≤37.5 morphine milligram equivalents (MMEs) during the inpatient postoperative stay did not require outpatient narcotic prescriptions. Thereafter, a strategy of matching inpatient use to outpatient prescription 1:1 in a linear regression model (p <0.001, R 2 0.55) optimally matched patient needs up to 200 MME. In the post-intervention survey, mean (SD) prescription decreased from 17.6 (13.7) MME to 8.4 (8.3) MME (p <0.01); 39% compared with 16% of women were discharged without a prescription (p <0.01); and amongst all patients 82.7% compared with 59.6% (p <0.01) had ≤4 pills remaining without differences in patient satisfaction or pain perception. CONCLUSION: This initiative highlights a practical approach to QI utilizing industry techniques in health care. This approach resulted in significant reductions in over-prescription and unused medication, without impacting pain or satisfaction scores. KEY POINTS: · 20% of patients may manage pain at home without opioids.. · In-hospital opioid use is reflective of outpatient need.. · Customize prescriptions to reduce leftover narcotics..

Hyperoxia-induced Cellular Senescence in Fetal Airway Smooth Muscle Cells.

Supplemental O2 (hyperoxia; 30-90% O2) is a necessary intervention for premature infants, but it contributes to development of neonatal and pediatric asthma, necessitating better understanding of contributory mechanisms in hyperoxia-induced changes to airway structure and function. In adults, environmental stressors promote formation of senescent cells that secrete factors (senescence-associated secretory phenotype), which can be inflammatory and have paracrine effects that enhance chronic lung diseases. Hyperoxia-induced changes in airway structure and function are mediated in part by effects on airway smooth muscle (ASM). In the present study, using human fetal ASM cells as a model of prematurity, we ascertained the effects of clinically relevant moderate hyperoxia (40% O2) on cellular senescence. Fetal ASM exposed to 40% O2 for 7 days exhibited elevated concentrations of senescence-associated markers, including ß-galactosidase; cell cycle checkpoint proteins p16, p21, and p-p53; and the DNA damage marker p-γH2A.X (phosphorylated γ-histone family member X). The combination of dasatinib and quercetin, compounds known to eliminate senescent cells (senolytics), reduced the number of hyperoxia-exposed ß-galactosidase-, p21-, p16-, and p-γH2A.X-positive ASM cells. The senescence-associated secretory phenotype profile of hyperoxia-exposed cells included both profibrotic and proinflammatory mediators. Naive ASM exposed to media from hyperoxia-exposed senescent cells exhibited increased collagen and fibronectin and higher contractility. Our data show that induction of cellular senescence by hyperoxia leads to secretion of inflammatory factors and has a functional effect on naive ASM. Cellular senescence in the airway may thus contribute to pediatric airway disease in the context of sequelae of preterm birth.

Cellular senescence in the lung across the age spectrum.

Cellular senescence results in cell cycle arrest with secretion of cytokines, chemokines, growth factors, and remodeling proteins (senescence-associated secretory phenotype; SASP) that have autocrine and paracrine effects on the tissue microenvironment. SASP can promote remodeling, inflammation, infectious susceptibility, angiogenesis, and proliferation, while hindering tissue repair and regeneration. While the role of senescence and the contributions of senescent cells are increasingly recognized in the context of aging and a variety of disease states, relatively less is known regarding the portfolio and influences of senescent cells in normal lung growth and aging per se or in the induction or progression of lung diseases across the age spectrum such as bronchopulmonary dysplasia, asthma, chronic obstructive pulmonary disease, or pulmonary fibrosis. In this review, we introduce concepts of cellular senescence, the mechanisms involved in the induction of senescence, and the SASP portfolio that are relevant to lung cells, presenting the potential contribution of senescent cells and SASP to inflammation, hypercontractility, and remodeling/fibrosis: aspects critical to a range of lung diseases. The potential to blunt lung disease by targeting senescent cells using a novel class of drugs (senolytics) is discussed. Potential areas for future research on cellular senescence in the lung are identified.

Moderate hyperoxia induces senescence in developing human lung fibroblasts.

Hyperoxia exposure in premature infants increases the risk of subsequent lung diseases, such as asthma and bronchopulmonary dysplasia. Fibroblasts help maintain bronchial and alveolar integrity. Thus, understanding mechanisms by which hyperoxia influences fibroblasts is critical. Cellular senescence is increasingly recognized as important to the pathophysiology of multiple diseases. We hypothesized that clinically relevant moderate hyperoxia (<50% O2) induces senescence in developing fibroblasts. Using primary human fetal lung fibroblasts, we investigated effects of 40% O2 on senescence, endoplasmic reticulum (ER) stress, and autophagy pathways. Fibroblasts were exposed to 21% or 40% O2 for 7 days with etoposide as a positive control to induce senescence, evaluated by morphological changes, ß-galactosidase activity, and DNA damage markers. Senescence-associated secretory phenotype (SASP) profile of inflammatory and profibrotic markers was further assessed. Hyperoxia decreased proliferation but increased cell size. SA-ß-gal activity and DNA damage response, cell cycle arrest in G2/M phase, and marked upregulation of phosphorylated p53 and p21 were noted. Reduced autophagy was noted with hyperoxia. mRNA expression of proinflammatory and profibrotic factors (TNF-α, IL-1, IL-8, MMP3) was elevated by hyperoxia or etoposide. Hyperoxia increased several SASP factors (PAI-1, IL1-α, IL1-ß, IL-6, LAP, TNF-α). The secretome of senescent fibroblasts promoted extracellular matrix formation by naïve fibroblasts. Overall, we demonstrate that moderate hyperoxia enhances senescence in primary human fetal lung fibroblasts with reduced autophagy but not enhanced ER stress. The resulting SASP is profibrotic and may contribute to abnormal repair in the lung following hyperoxia.

Peripartum Cardiomyopathy and Preeclampsia: Overlapping Diseases of Pregnancy.

PURPOSE OF REVIEW: Hypertensive disorders of pregnancy (HDP) often result in cardiac dysfunction and have been variably included as a risk factor for peripartum cardiomyopathy (PPCM). However, there is debate regarding the relationship between the two entities. RECENT FINDINGS: Diastolic dysfunction appears to be more predominant among gravidas with HDP, while systolic dysfunction predominates in PPCM. However, this finding is not consistent in all studies. Recent examinations of mortality and morbidity associated with PPCM in the setting of HDP do not demonstrate a predominant pattern with a mixture of results. Further, right ventricular dysfunction is identified to be a common theme in both populations. From a basic science perspective, there is evidence to demonstrate a predominantly anti-angiogenic milieu in both PPCM and HDP. PPCM and HDP associated cardiomyopathy overlap significantly. As such, unifying theories for their pathophysiology should be investigated.

Predicting cesarean delivery among gravidas with morbid obesity-a machine learning approach.

BACKGROUND: Women with obesity have higher rates of complications following cesarean delivery, such as wound infection and endometritis, with risks being the highest if a cesarean delivery is performed after labor. Previous efforts at predicting whether a patient's labor course would ultimately result in cesarean delivery have been intermediate with area under the curve in the 0.75 to 78 range. OBJECTIVE: This study aimed to assess whether machine learning algorithms would outperform traditional modeling in developing a cesarean delivery prediction model among gravidas with morbid obesity (body mass index of ≥40 kg/m2) to determine whether a primary cesarean delivery may be beneficial. STUDY DESIGN: This was a secondary analysis of a retrospective cohort of 1298 patients with morbid obesity presenting for vaginal delivery at ≥37 weeks of gestation between 2011 and 2016 at a single institution. Data available at the time of admission and delivery were modeled using logistic regression, decision tree, random forest, and support vector modeling with evaluation of area under the curve, accuracy, sensitivity, and specificity. RESULTS: Logistic regression demonstrated an area under the curve of 0.816 (95% confidence interval, 0.810-0.817), which was superior to machine learning models when evaluating data at the time of delivery (demographic data, initial cervical examinations, comorbidities, and obstetrical interventions) (P<.001). However, there was no significant difference between most machine learning models and logistic regression area under the curve of 0.799 (95% confidence interval, 0.795-0.804) when evaluating parameters available at the time of admission (demographic data, initial cervical examinations, and comorbidities). Race was noted to be a significant predictor in both models (P<.001). CONCLUSION: Machine learning and traditional modeling techniques are likely equivalent concerning cesarean delivery prediction in this population. The models developed showed good discrimination and may be used to guide clinical decision-making concerning the optimal mode of delivery.

An imbalance-aware deep neural network for early prediction of preeclampsia.

Preeclampsia (PE) is a hypertensive complication affecting 8-10% of US pregnancies annually. While there is no cure for PE, aspirin may reduce complications for those at high risk for PE. Furthermore, PE disproportionately affects racial minorities, with a higher burden of morbidity and mortality. Previous studies have shown early prediction of PE would allow for prevention. We approached the prediction of PE using a new method based on a cost-sensitive deep neural network (CSDNN) by considering the severe imbalance and sparse nature of the data, as well as racial disparities. We validated our model using large extant rich data sources that represent a diverse cohort of minority populations in the US. These include Texas Public Use Data Files (PUDF), Oklahoma PUDF, and the Magee Obstetric Medical and Infant (MOMI) databases. We identified the most influential clinical and demographic features (predictor variables) relevant to PE for both general populations and smaller racial groups. We also investigated the effectiveness of multiple network architectures using three hyperparameter optimization algorithms: Bayesian optimization, Hyperband, and random search. Our proposed models equipped with focal loss function yield superior and reliable prediction performance compared with the state-of-the-art techniques with an average area under the curve (AUC) of 66.3% and 63.5% for the Texas and Oklahoma PUDF respectively, while the CSDNN model with weighted cross-entropy loss function outperforms with an AUC of 76.5% for the MOMI data. Furthermore, our CSDNN model equipped with focal loss function leads to an AUC of 66.7% for Texas African American and 57.1% for Native American. The best results are obtained with 62.3% AUC with CSDNN with weighted cross-entropy loss function for Oklahoma African American, 58% AUC with DNN and balanced batch for Oklahoma Native American, and 72.4% AUC using either CSDNN with weighted cross-entropy loss function or CSDNN with focal loss with balanced batch method for MOMI African American dataset. Our results provide the first evidence of the predictive power of clinical databases for PE prediction among minority populations.

Safety of salpingectomy at time of delivery.

OBJECTIVE: The most common methods of sterilization during cesarean delivery rely on excision of a mid-segment of the fallopian tube. Contemporary data suggest ovarian cancers may originate in the fimbriae of the fallopian tube; therefore, a strategy of prophylactic salpingectomy (SL) has been adopted during gynecologic surgery. The purpose of this study was to evaluate the safety of SL compared to traditional mid-segment excision at time of cesarean and after vaginal delivery through change in perioperative hemoglobin (Hgb). STUDY DESIGN: We retrospectively evaluated patients undergoing sterilization concurrent with cesarean delivery or in the post-vaginal delivery period between 1 January 2015 and 31 December 2017 in the Mayo Clinic Health System; a community-based practice. In order to test for non-inferiority, 30 patients in each arm (tubal ligation (TL) and SL) were required to detect a pre- and post-operative Hgb difference of 0.5 mg/dL between groups with a power of 80%. Exclusion criteria included: age <18 years, BMI >50 kg/m2, endometriosis, other concurrent surgical procedures, bleeding disorders, postpartum hemorrhage due to atony, trial of labor after cesarean (TOLAC), and the presence of ovarian masses. RESULTS: One hundred fifty-two patients met inclusion criteria. There was no evidence of inferiority in either the post-vaginal delivery or the cesarean groups with a mean difference in pre- and post-op Hgb of 0.18 mg/dL (p = .99) post-cesarean and 0.04 mg/dL post-vaginal delivery with less reduction in Hgb from SL. The mean length of the procedure was 10.0 and 9.9 min (p = .005) longer for SL procedures amongst cesarean and postpartum procedures, respectively. Subgroup analyses did not demonstrate differences in blood loss between different techniques. Clamp-cut-tie techniques took longer than all other procedures in both groups. CONCLUSION: This study provides evidence that the practice of salpingectomy at the time of cesarean and post-vaginal delivery may be safe and should form the basis of prospective trials.

Management of Complicated Monochorionic Twin Gestations: An Evidence-Based Protocol.

IMPORTANCE: Monochorionic (MC) twins are hemodynamically connected by vascular anastomoses within the single shared placenta. The transfer of fluid or blood from one fetus to the other may result in development of pathologic complications, such as twin-twin transfusion syndrome, twin anemia polycythemia sequence, selective intrauterine growth restriction, and twin reversed arterial perfusion sequence. Monoamniotic gestations, which comprise a small fraction of MC pregnancies, can also present with unique challenges, particularly antepartum umbilical cord entanglement. All these complications carry a high risk of fetal morbidity and mortality if not recognized and managed in a timely fashion. OBJECTIVE: The purpose of this article is to review evidence-based management of complicated MC twin gestations and propose a standardized approach to surveillance. EVIDENCE ACQUISITION: Monochorionic gestations account for the majority of complications that occur in twin pregnancies; however, there is unclear evidence on the appropriate surveillance for and management of specific complications associated with these pregnancies. RESULTS: This article summarizes management for each specific type of MC complication in a structured and clear manner. CONCLUSIONS: Early pregnancy ultrasound, ideally between 10 and 13 weeks' gestation, is critical for the diagnosis and characterization of twin pregnancies. To improve outcomes for MC twins, appropriate fetal surveillance should be initiated at 16 weeks' gestation and continued until delivery.

Intra-incisional liposomal bupivacaine and its impact on postcesarean analgesia: a retrospective study.

PURPOSE: The efficacy of long-acting intraincisional bupivacaine in reducing postoperative opioid use among women who have undergone a cesarean is currently unknown. MATERIALS AND METHODS: This was a retrospective case-control study with a 1:1 allocation. We identified 40 patients in each group, for a total of 80. The treatment group was administered 266 mg of liposomal bupivacaine after completion of the cesarean and was compared to historical controls. Data regarding anesthesia administered, opioid consumption, nonsteroidal anti-inflammatory use, acetaminophen use, type of cesarean, reason for cesarean, and length of postoperative stay were recorded. RESULTS: The treatment group used 41.51 mg of morphine equivalents, while the control group consumed 69.90 mg (p < .001); multivariate analysis demonstrated a mean difference of 26.52 mg (95%CI 12.76-40.28). Univariate analysis demonstrated mean difference in intravenous (IV) ketorolac (40.77 mg, p < .001) and IV acetaminophen (1333.33 mg, p < .001) was different and greater in the treatment group; this was controlled for in the multivariate model. There was no difference in oral and IV ibuprofen or oral acetaminophen use between groups. There were no differences between the type of anesthesia, length of stay, reason for cesarean, and classical sections between groups. CONCLUSIONS: Incisional administration of liposomal bupivacaine may be an effective adjunct in reducing opioid use postoperatively and may be a useful adjunct within an enhanced recovery program.

Asymptomatic Bacteriuria in Pregnancy Complicated by Pyelonephritis Requiring Nephrectomy.

Routine prenatal care in the United States includes screening for asymptomatic bacteriuria (ASB), which occurs in 2 to 7 percent of pregnant women and can cause urinary tract infection and pyelonephritis. We present the case of a pregnant woman affected by multidrug resistant Klebsiella induced ASB during her prenatal screen, which was untreated due to a repeat urine culture showing mixed flora; subsequently, the patient's postpartum course was complicated by pyelonephritis and perinephric abscess, concluding in a radical nephrectomy. Current recommendations are to treat ASB after two consecutive voided urine cultures showing the same bacterial strain in quantitative counts of =/> 10(5) colony forming units (cfu)/mL or a single-catheterized specimen with quantitative count of =/> 10(2) cfu/mL. For women with ASB in their prenatal screen or other high risk factors, consideration should be given to testing urine cultures every trimester until the completion of pregnancy to prevent the complications of persistent bacteriuria.

Burns During Pregnancy: Implications for Maternal-Perinatal Providers and Guidelines for Practice.

IMPORTANCE: When a major burn is suffered during pregnancy, the obstetric provider is challenged to respond on an evidence basis because personal experience usually is lacking. Currently, there is a paucity of publications to inform the obstetrician, guide practice, and impact early critical decision making. OBJECTIVE: The aims of this study were to summarize the available information on early management of burns during pregnancy and to identify components of best practices for optimal outcome. EVIDENCE ACQUISITION: The PubMed database was searched for relevant titles and abstracts involving pregnant patients suffering from second-/third-degree burns. Among these studies, the bibliographies were investigated for further relevant literature. A total of 114 studies were identified during the initial search, and only studies published in English and French were included for a total of 42. Variable data were available for 1141 patients, with complete data for 139 cases. Mediation and regression analysis were used for available data. Insufficient data were available to undertake a systematic review. RESULTS: Total body surface area of burns (TBSAB) was positively associated with maternal death, and the odds of maternal mortality increase by 1.08 per percentage increase of TBSAB (P < 0.001). Fetal survival depends on maternal survival (P ≤ 0.001). Maternal survival declines incrementally when TBSAB exceeds 55%, and inhalation injury further exacerbates maternal-perinatal risk. CONCLUSIONS: Emergent assessment of the pregnant burn victimincludes determination of gestational age, extent of TBSAB, presence of inhalation injury, and continuous fetal monitoring. If gestational age is 24 weeks or longer and TBSAB exceeds 55%, urgent cesarean delivery appears desirable for the mother and baby. RELEVANCE: A specific analysis of maternal-perinatal outcome based on TBSAB and gestational age is relevant to obstetric and emergency providers who provide care to pregnant burn patients.