bluuebunny/crossref_metadata_2025_split huggingface dataset:
2,4,6-Tribromophenol Disposition and Kinetics in Rodents: Effects of Dose, Route, Sex, and Species
Authors: Knudsen Gabriel A , Trexler Andrew W , Richards Alicia C , Hall Samantha M , Hughes Michael F , Birnbaum Linda S 
Published: February 2019

Abstract
2,4,6-tribromophenol (TBP, CAS No. 118-79-6) is widely used as a brominated flame retardant and wood antifungal agent. TBP is frequently detected in environmental matrices, biota, and humans. In female SD rats, systemically available TBP (10 µmol/kg, IV) was rapidly excreted primarily via urine, with approximately 61% of the dose recovered after 4 h, and 89%–94% in 24 h; 5% was recovered in feces; and 1%–2% in blood/tissues. TBP administered to female SD rats (0.1–1000 µmol/kg) by gavage was well absorbed, with approximately 25% eliminated via urine after 4 h and approximately 88% after 24 h. Approximately 11% of a single oral dose was recovered in bile. Male SD rats and B6C3F1/J mice of both sexes had similar disposition profiles when administered a single oral dose of TBP (10 µmol/kg). Following administration, fecal recoveries varied only slightly by dose, sex, or species. TBP readily passed unchanged through both human (ex vivo only) and rat skin with between 55% and 85% of a 100 nmol/cm2 passing into or through skin. Concentrations of TBP in blood fit a two-compartment model after IV-dosing and a one-compartment model after oral dosing. Urine contained a mixture of TBP, TBP-glucuronide, and TBP-sulfate. Fecal extracts contained only parent TBP whereas bile contained only TBP-glucuronide. TBP did not appear to bioaccumulate or alter its own metabolism after repeated administration. TBP was readily absorbed at all doses and routes tested with an oral bioavailability of 23%–27%; 49% of TBP is expected to be dermally bioavailable in humans. From these data, we conclude that humans are likely to have significant systemic exposure when TBP is ingested or dermal exposure occurs.
Hyperbaric Versus Isobaric Bupivacaine for Spinal Anaesthesia for Elective Cesarean Section: A Cochrane Systematic Review
Authors: Sng B.L. , Han N.L.R. , Leong W.L. , Sultana R. , Siddiqui F.J. , Assam P.N. , Chan E.S. , Tan K.H. , Sia A.T. 
Published: February 2019

(Anaesthesia. 2018;73:499–511)
Bupivacaine is the most commonly used local anesthetic for cesarean delivery performed with spinal anesthesia. It is usually available in in both isobaric and hyperbaric formulations. Although both formulations have been widely used, the difference in density between the 2 may result in differing diffusion patterns and distribution after intrathecal injection. While some studies have suggested that hyperbaric and isobaric bupivacaine differ in some block characteristics, such as motor blockade and duration of action, the superiority of one formulation over the other has not been determined. Therefore, this Cochrane systematic review and meta-analysis was performed to determine the efficacy and safety of hyperbaric bupivacaine compared with isobaric bupivacaine for spinal anesthesia in women undergoing elective cesarean delivery.
Randomized Controlled Trial of the Clinical Efficacy of Multiport Versus Uniport Wire-reinforced Flexible Catheters for Labor Epidural Analgesia
Authors: Philip J. , Sharma S.K. , Sparks T.J. , Reisch J.S. 
Published: February 2019

(Anesth Analg. 2018;126(2):537–544)
When using epidural catheters that are not reinforced with a wire, multiport catheters provide improved epidural analgesia during labor (LEA) as compared with a single port catheter. Wire-reinforced flexible catheters, a recent advancement in epidural catheter design, have not been evaluated in this context. In the present study, the authors compared multiport and single-port wire-reinforced flexible catheters to determine whether the number of ports affects analgesia during lumbar epidural labor analgesia.
UK Confidential Enquiry into Maternal Deaths: Still Learning to Save Mothers’ Lives
Authors: Lucas D.N. , Bamber J.H. 
Published: February 2019

(Anaesthesia. 2018;73:407–420)
This editorial summarized results from the fourth report of the Confidential Enquiry into Maternal Deaths and Morbidity from the MBRRACE-UK collaboration and provided commentary about some of the findings.
Neonatal Abstinence Syndrome: Advances in Diagnosis and Treatment
Authors: Wachman E.M. , Schiff D.M. , Silverstein M. 
Published: February 2019

(JAMA. 2018;319(13):1362–1374)
The signs and symptoms of withdrawal that infants develop after in utero exposure to opioids is referred to as neonatal abstinence syndrome (NAS). The US Pediatric Health Information System reports the incidence of NAS has increased 5-fold since 2000. The incidence was 20 per 1000 live births in 2016, and in utero opioid exposure adversely influenced the neurodevelopmental status of the exposed children. Infants with severe withdrawal symptoms require pharmacologic intervention with replacement opioids such as methadone or morphine, and then are weaned off over days to weeks. Currently, there is no consensus regarding the best diagnostic or treatment strategies. This review summarized the approaches to the diagnosis and treatment of NAS published during the past 10 years. The outcomes of infant nonpharmacologic and pharmacologic treatment as well as maternal pharmacologic treatment were also summarized.
Clinical Evidence for Any Effect of Anesthesia on the Developing Brain
Authors: Davidson A.J. , Sun L.S. 
Published: February 2019

(Anesthesiology. 2018;128:840–853)
The US Food and Drug Administration (FDA) recently warned against the repeated or prolonged exposure to general anesthesia in children and mothers in the third trimester of pregnancy due to potential effects on brain development. The warning suggests that brief exposure may be safe. Significant research has been conducted over the last decade. However, much of the data have come from animal rather than human studies. It is unclear exactly how anesthetic agents affect aspects of human brain development, if they do at all. This review summarized current human studies and the evidence available.
Postpartum Care in the United States: New Policies for a New Paradigm
Authors: Murray Horwitz M.E. , Molina R.L. , Snowden J.M. 
Published: February 2019

(N Engl J Med. 2018;379:1691–1693)
Postpartum care today in the United States generally consists of an “arbitrary 6-week check.” Consequently, in April 2018, the American College of Obstetricians and Gynecologists (ACOG) called for a new paradigm for postpartum care, which extends the 6-week postpartum single-visit to a 12-week “4th trimester” and reframes postpartum care as an ongoing, individualized process.
HELLP Syndrome, Risk Factors in First and Second Pregnancy: A Population-based Cohort Study
Authors: Malmström O. , Morken N.H. 
Published: February 2019

(Acta Obstet Gynecol Scand. 2018;97:709–716)
HELLP syndrome (hemolysis, elevated liver enzymes, and low platelet count) is a rare disorder and is currently considered a form of severe preeclampsia. There may be specific risk factors for HELLP syndrome that differ from those for other forms of preeclampsia. In addition, the risk factors for HELLP syndrome may vary between the first and second pregnancies. Currently, population-based data on HELLP syndrome are limited. This study aimed to use a national birth registry to estimate the risks of developing HELLP syndrome in first and second pregnancies based on the presence of potential risk factors. In addition, the effect of adverse outcomes in the first pregnancy on the risk of HELLP syndrome in the second pregnancy was evaluated.
A Retrospective Analysis of Factors Associated With Anesthetic Case Duration for Cesarean Deliveries
Authors: Harris M.J. , Gabriel R.A. , Dutton R.P. , Urman R.D. 
Published: February 2019

(Int J Obstet Anesth. 2018;34:42–49)
Anesthesia practices must have a thorough understanding of the factors that can affect their staffing models as they are faced with the need to provide appropriate and accessible obstetric anesthesia care in the midst of tighter budgets and shrinking reimbursements being encountered by many anesthesiology departments. The ability of a facility to predict cesarean delivery (CD) case duration, manage case volumes, design optimal protocols, and ensure adequate availability of obstetric anesthesiologists will improve patient outcomes and support appropriate resource utilization. It can be difficult, however, to predict case duration. Understanding what factors affect duration would help with developing the most appropriate staffing models that lead to the highest quality care while being cost-effective. The objectives of this study were to describe the variability of case duration of CDs in the United States based on hospital facility type (eg, size, university versus nonuniversity hospitals), region of the country, time of day, hospital case volume, patient characteristics, and provider characteristics.
Long-term Mortality Risk and Life Expectancy Following Recurrent Hypertensive Disease of Pregnancy
Authors: Theilen L.H. , Meeks H. , Fraser A. , Esplin M.S. , Smith K.R. , Varner M.W. 
Published: February 2019

(Am J Obstet Gynecol. 2018;219:107.e1–e6)
Hypertensive disease of pregnancy has been associated with early mortality from cardiovascular disease. However, there is currently no data available on the relationship between recurrent pregnancies complicated by any hypertensive disease of pregnancy and all-cause mortality in the United States. This study aims to bridge this knowledge gap and compare the risk of early mortality between women with recurrent hypertensive disease of pregnancy and women with 0 affected pregnancies or 1 affected pregnancy.
Old Ways Do Not Open New Doors: Norepinephrine for First-line Treatment of Spinal Hypotension
Authors: Vallejo M.C. , Zakowski M.I. 
Published: February 2019

(Anesth Analg. 2018;126:1809–1811)
Although phenylephrine is the first-choice vasopressor for the prevention and treatment of maternal hypotension during spinal anesthesia for cesarean delivery, its sole action as an alpha-adrenergic agonist can cause significant dose-dependent bradycardia, which in turn, may compromise fetal health. Consequently, norepinephrine, which has both alpha-1-adrenergic and beta-1-adrenergic activity has been proposed as an alternative.
Development of the TeamOBS-PPH: Targeting Clinical Performance in Postpartum Hemorrhage
Authors: Brogaard L. , Hvidman L. , Hinshaw K. , Kierkegaard O. , Manser T. , Musaeus P. , Arafeh J. , Daniels K.I. , Judy A.E. , Uldbjerg N. 
Published: February 2019

(Acta Obstet Gynecol Scand. 2018;97:677–687)
The most frequent cause of maternal death worldwide is major postpartum hemorrhage (PPH), defined as blood loss of 1000 mL or more within 24 hours of delivery. If a clinical team performs well, the risk of maternal death from PPH can be significantly reduced. Previous studies of PPH management have focused primarily on assessment of outcome, nontechnical performance, and technical performance. There is a paucity of literature, however, on the evaluation of clinical performance during PPH, which assesses the quality of the actual patient care provided. This study aimed to develop a tool for the assessment of clinical performance during PPH and to evaluate the reliability and validity of that tool using video recordings of PPH management of obstetric teams in both real-life situations and simulations.
Pulse Pressure and Carotid Artery Doppler Velocimetry as Indicators of Maternal Volume Status: A Prospective Cohort Study
Authors: Lappen J.R. , Myers S.A. , Bolden N. , Shaman Z. , Angirekula V. , Chien E.K. 
Published: February 2019

(Anesth Analg. 2018;127:457–464)
Not only is pregnancy associated with numerous physiological cardiovascular changes that influence maternal volume status, but neuraxial analgesia also significantly alters the maternal hemodynamic profile. Noninvasive techniques to assess intravascular volume are thereby critical to intrapartum fluid management in the obstetric population. Neither pulse pressure nor the carotid artery Doppler response to passive leg raise (PLR) has been prospectively evaluated in an obstetric population for the assessment of volume status. Therefore, the authors of the present study tested the hypothesis that carotid artery Doppler response to PLR is greater in women with a narrow pulse pressure, indicating relative hypovolemia.
Hemoglobinopathies in the Fetal Position
Authors: Pasricha S.R. , Drakesmith H. 
Published: February 2019

(N Engl J Med. 2018;379:1675–1677)
Hemoglobinopathies are disorders caused by mutations in genes that encode globins and include sickle cell disease and β-thalassemia. It has been reported that adults with these hemoglobinopathies who have comparatively high levels of fetal hemoglobin (HbF) have better clinical outcomes than those with low levels of HbF. While drugs like hydroxyurea increase HbF levels, thereby reducing the severity of symptoms of hemoglobinopathies, a drug that more effectively increases HbF levels is the holy grail of hemoglobinopathy research.
A Systematic Review of DURAL Puncture Epidural Analgesia for Labor
Authors: Layera S. , Bravo D. , Aliste J. , Tran Q. 
Published: February 2019

(J Clin Anesth. 2019;53:5–10)
Combined spinal epidural analgesia (CSEA) has the benefit of shorter onset time, decreased motor blockade, and more reliable analgesia. However, intrathecal local anesthesia (LA) injection may obscure the response of the test dose used to exclude inadvertent subarachnoid placement of the epidural catheter. Dural puncture epidural analgesia (DPEA), in which no LA is deposited in the subarachnoid space, is a potential means of labor analgesia that avoids this effect. Benefits of DPEA remain unproven. In this systematic review, authors discussed the evidence available from randomized controlled trials and compared DPEA and lumbar epidural analgesia (LEA) for labor analgesia.
Intravenous Dexamethasone for Prophylaxis of Postoperative Nausea and Vomiting After Administration of Long-acting Neuraxial Opioids: A Systematic Review and Meta-Analysis
Authors: Grape S. , Usmanova I. , Kirkham K.R. , Albrecht E. 
Published: February 2019

(Anaesthesia. 2018;73:480–489)
Long-acting neuraxial opioids provide excellent analgesia following surgery, but they have also been known to contribute to postoperative nausea and vomiting, thereby negatively affecting postoperative recovery and patient experience. Intravenous (iv) dexamethasone is an effective antiemetic against postoperative nausea and vomiting associated with general anesthesia, but its efficacy in preventing nausea and vomiting related to the administration of long-acting neuraxial opioids for postoperative analgesia remains undetermined. The aim of this systematic review and meta-analysis was to assess the efficacy of iv dexamethasone as a prophylactic antiemetic in surgical patients receiving long-acting intrathecal or epidural opioids.
Building High-Performing Teams in Academic Surgery: The Opportunities and Challenges of Inclusive Recruitment Strategies
Authors: Dossett Lesly A. , Mulholland Michael W. , Newman Erika A. 
Published: February 2019

Problem
In academic surgery, women and physicians from ethnic minority groups remain inadequately represented relative to their representation in the U.S. population and among medical students and surgical trainees. Although several initiatives have been aimed at developing the academic surgery pipeline or addressing issues related to faculty retention and promotion, little is known about how recruitment practices impact diversity in academic medicine. Moreover, national standards and ideal practices specific for effective recruitment in surgery have not been established.

Approach
A working group at the Department of Surgery at the University of Michigan implemented an inclusive search and selection process for all open faculty positions within the department in academic year 2017–2018. The strategy included mandatory training, a standing recruitment committee with diverse membership, broad promotion of positions, implementing a modified “Rooney rule,” panel interviews of candidates, standardized interview protocols, a standardized evaluation tool and scoring system, and written evaluations/ranking of candidates.

Outcomes
Implementation of this recruitment strategy resulted in several immediate measurable benefits including increased diversity of the applicant pools and of new faculty hires. In addition to these positive effects, the department noted several knowledge gaps and faced challenges to implementing all elements of the strategy.

Next Steps
The authors share their framework, highlighting opportunities and challenges that are broadly generalizable and relevant for building high-performing teams in academic medicine. Work to set measurable metrics and address challenges for inclusive recruitment in surgery is ongoing. Such evaluation and refinement are important for sustainability and increasing effectiveness.
Critical flickering frequency test: a diagnostic tool for minimal hepatic encephalopathy
Authors: Metwally Mohamed A. , Biomy Hosam A. , Omar Maha Z. , Sakr Ahmed I. 
Published: February 2019

Background
Minimal hepatic encephalopathy (MHE) is underestimated. It affects 30–55% of patients with liver cirrhosis and can change their daily functions. Psychometric tests are sensitive in diagnosing MHE, but interpretation is difficult. Availability of a simpler diagnostic tool for MHE is mandatory. Critical flicker frequency (CFF) is a simple diagnostic test.

Aim
The aim of this study was to assess the diagnostic accuracy of CFF test for MHE.

Patients and methods
A total of 86 patients with cirrhosis with negative history of overt hepatic encephalopathy were included. History, clinical examination, laboratory investigations, and abdominal ultrasonography data were collected. Arabic version of number connection test, serial dotting test, and line tracing test were done. Total psychometric hepatic encephalopathy score (PHES) was used to diagnose MHE. CFF was done for all patients with MHE diagnosis at 39 Hz.

Results
Of the 86 patients, 45 (52.3%) had MHE with PHES. Patients with MHE had significantly older age, presentation with jaundice, ascites, lower hemoglobin level, lower serum albumin, prolonged INR, higher Child class and score (P≤0.001), and higher model of end stage liver disease score (P=0.001) than patients without MHE. In comparison with PHES, CFF has a sensitivity of 91.1±8.32%, specificity of 92.7±7.96%, positive predictive value of 93.2±7.44%, and negative predictive value of 90.4±8.91%. In receiver operating characteristic curve, CFF is excellent in diagnosis of MHE, with area under the curve 0.937 (P<0.001).

Conclusion
MHE is common among patients with liver cirrhosis. CFF is a simple, rapid, noninvasive test for diagnosis of MHE, with a very good accuracy at 39 Hz.
A nomogram predicting the need for bleeding interventions after high-grade renal trauma: Results from the American Association for the Surgery of Trauma Multi-institutional Genito-Urinary Trauma Study (MiGUTS)
Authors: Keihani Sorena , Rogers Douglas M. , Putbrese Bryn E. , Moses Rachel A. , Zhang Chong , Presson Angela P. , Hotaling James M. , Nirula Raminder , Luo-Owen Xian , Mukherjee Kaushik , Morris Bradley J. , Majercik Sarah , Piotrowski Joshua , Dodgion Christopher M. , Schwartz Ian , Elliott Sean P. , DeSoucy Erik S. , Zakaluzny Scott , Sherwood Brenton G. , Erickson Bradley A. , Baradaran Nima , Breyer Benjamin N. , Smith Brian P. , Okafor Barbara U. , Askari Reza , Miller Brandi , Santucci Richard A. , Carrick Matthew M. , Kocik Jurek F. , Hewitt Timothy , Burks Frank N. , Heilbrun Marta E. , Myers Jeremy B. 
Published: February 2019

BACKGROUND
The management of high-grade renal trauma (HGRT) and the indications for intervention are not well defined. The American Association for the Surgery of Trauma (AAST) renal grading does not incorporate some important clinical and radiologic variables associated with increased risk of interventions. We aimed to use data from a multi-institutional contemporary cohort to develop a nomogram predicting risk of interventions for bleeding after HGRT.

METHODS
From 2014 to 2017, data on adult HGRT (AAST grades III–V) were collected from 14 level 1 trauma centers. Patients with both clinical and radiologic data were included. Data were gathered on demographics, injury characteristics, management, and outcomes. Clinical and radiologic parameters, obtained after trauma evaluation, were used to predict renal bleeding interventions. We developed a prediction model by applying backward model selection to a logistic regression model and built a nomogram using the selected model.

RESULTS
A total of 326 patients met the inclusion criteria. Mechanism of injury was blunt in 81%. Median age and injury severity score were 28 years and 22, respectively. Injuries were reported as AAST grades III (60%), IV (33%), and V (7%). Overall, 47 (14%) underwent interventions for bleeding control including 19 renal angioembolizations, 16 nephrectomies, and 12 other procedures. Of the variables included in the nomogram, a hematoma size of 12 cm contributed the most points, followed by penetrating trauma mechanism, vascular contrast extravasation, pararenal hematoma extension, concomitant injuries, and shock. The area under the receiver operating characteristic curve was 0.83 (95% confidence interval, 0.81–0.85).

CONCLUSION
We developed a nomogram that integrates multiple clinical and radiologic factors readily available upon assessment of patients with HGRT and can provide predicted probability for bleeding interventions. This nomogram may help in guiding appropriate management of HGRT and decreasing unnecessary interventions.

LEVEL OF EVIDENCE
Prognostic and epidemiological study, level III.
Leveraging genetic interaction for adverse drug-drug interaction prediction
Authors: Qian Sheng , Liang Siqi , Yu Haiyuan 
Published: February 2019

ABSTRACTIn light of increased co-prescription of multiple drugs, the ability to discern and predict drug-drug interactions (DDI) has become crucial to guarantee the safety of patients undergoing treatment with multiple drugs. However, information on DDI profiles is incomplete and the experimental determination of DDIs is labor-intensive and time-consuming. Although previous studies have explored various feature spaces for in silico screening of interacting drug pairs, no method currently provides reliable predictions outside of their training sets. Here we demonstrate for the first time targets of adversely interacting drug pairs are significantly more likely to have synergistic genetic interactions than non-interacting drug pairs. Leveraging genetic interaction features and a novel training scheme, we construct a gradient boosting-based classifier that achieves robust DDI prediction even for drugs whose interaction profiles are completely unseen during training. We demonstrate that in addition to classification power—including the prediction of 432 novel DDIs—our genetic interaction approach offers interpretability by providing plausible mechanistic insights into the mode of action of DDIs.