Placental growth factor (alone or in combination with soluble fms-like tyrosine kinase 1) as an aid to the assessment of women with suspected pre-eclampsia: systematic review and economic analysis

Background: Pre-eclampsia (PE) prediction based on blood pressure, presence of protein in the urine, symptoms and laboratory test abnormalities can result in false-positive diagnoses. This may lead to unnecessary antenatal admissions and preterm delivery. Blood tests that measure placental growth factor (PlGF) or the ratio of soluble fms-like tyrosine kinase 1 (sFlt-1) to PlGF could aid prediction of PE if either were added to routine clinical assessment or used as a replacement for proteinuria testing.Objectives: To evaluate the diagnostic accuracy and cost-effectiveness of PlGF-based tests for patients referred to secondary care with suspected PE in weeks 20–37 of pregnancy.Design: Systematic reviews and an economic analysis.Data sources: Bibliographic databases including MEDLINE, EMBASE, Web of Science and The Cochrane Library and Database of Abstracts of Reviews of Effects were searched up to July 2015 for English-language references. Conferences, websites, systematic reviews and confidential company submissions were also accessed.Review methods: Systematic reviews of test accuracy and economic studies were conducted to inform an economic analysis. Test accuracy studies were required to include women with suspected PE and report quantitatively the accuracy of PlGF-based tests; their risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS) criteria. The economic studies review had broad eligibility criteria to capture any types of economic analysis; critical appraisal employed standard checklists consistent with National Institute for Health and Care Excellence criteria. Study selection, critical appraisal and data extraction in both reviews were performed by two reviewers.Economic analysis: An independent economic analysis was conducted based on a decision tree model, using the best evidence available. The model evaluates costs (2014, GBP) from a NHS and Personal Social Services perspective. Given the short analysis time horizon, no discounting was undertaken.Results: Four studies were included in the systematic review of test accuracy: two on Alere’s Triage® PlGF test (Alere, Inc., San Diego, CA, USA) for predicting PE requiring delivery within a specified time and two on Roche Diagnostics’ Elecsys® sFlt-1 to PlGF ratio test (Roche Diagnostics GmbH, Mannheim, Germany) for predicting PE within a specified time. Three studies were included in the systematic review of economic studies, and two confidential company economic analyses were assessed separately. Study heterogeneity precluded meta-analyses of test accuracy or cost-analysis outcomes, so narrative syntheses were conductedto inform the independent economic model. The model predicts that, when supplementing routine clinical assessment for rule-out and rule-in of PE, the two tests would be cost-saving in weeks 20–35 of gestation, and marginally cost-saving in weeks 35–37, but with minuscule impact on quality of life. Length of neonatal intensive care unit stay was the most influential parameter in sensitivity analyses. All othersensitivity analyses had negligible effects on results.Limitations: No head-to-head comparisons of the tests were identified. No studies investigated accuracy of PlGF-based tests when used as a replacement for proteinuria testing. Test accuracy studies were found to be at high risk of clinical review bias.Conclusions: The Triage and Elecsys tests would save money if added to routine clinical assessment for PE. The magnitude of savings is uncertain, but the tests remain cost-saving under worst-case assumptions. Further research is required to clarify how the test results would be interpreted and applied in clinical practice.Study registration: This study is registered as PROSPERO CRD42015017670.Funding: The National Institute for Health Research Health Technology Assessment programme

Office bladder distention with Electromotive Drug Administration (EMDA) is equivalent to distention under General Anesthesia (GA)

BACKGROUND: Bladder distention is commonly used in diagnosis and treatment of interstitial cystitis (IC). Traditionally performed in the operating room under general or spinal anesthesia (GA), it is expensive and associated with short term morbidity. Office bladder distention using electromotive drug administration (EMDA) has been suggested as an alternative that is well tolerated by patients. We report the first comparative findings of patients undergoing both office distention with EMDA and distention in the operating room (OR) with GA. METHODS: This retrospective chart review identified 11 patients participating in two protocols of EMDA bladder distention who also underwent bladder distention under GA either prior to or after the EMDA procedure. RESULTS: The median absolute difference in bladder capacity between GA and EMDA was only 25 cc; the median percent difference was 5%. Cystoscopic findings, while not prospectively compiled, appear to have been similar. CONCLUSION: This study represents the first comparison between distention with EMDA versus GA and confirms the technical feasibility of performing bladder distention in an office setting. The distention capacity achieved in the office was nearly identical to that in the OR and the cystoscopic findings very similar. Further investigation into the comparative morbidity, cost, and other outcome measures is warranted to define the ultimate role of EMDA bladder distention in the clinical evaluation and care of patients with IC

Ferric iron geometry and coordination during hydrolysis and ferrihydrite precipitation

Definitive structural characterisation of ferrihydrite has challenged scientists primarily due to its nanosized particles and inherent long-range structural disorder which challenges analytical methodology (and modelling) typically employed to determine the structure of minerals. Here we report on the application of a synchrotron quick-scanning X-ray absorption spectroscopy (XAS) approach, which allows the collection of Extended X-ray Absorption Fine Structure (EXAFS) spectral data to k = 15 Å-1 in < 1 minute, to obtain unparalleled iron Kedge data on the hydrolysis of FeIII(H2O)6 and ferrihydrite precipitation. Modelling of the pre-edge and EXAFS data: 1) supports theoretical studies which have suggested the existence of a monomeric penta-coordinated FeIII hydrolysis species and; 2) corroborates recently proposed structural models of ferrihydrite that contain tetrahedral FeIII. Modelling results indicate that ferrihydrite consists of 15 to 25 % tetrahedral FeIII and suggest that this geometry must be included in any comprehensive structural model of ferrihydrite and, furthermore, should be considered when evaluating the reactivity, stability and other structure-property relationships of this mineral. © The Authors

Effect of preoperative administration of atenolol to dogs with pulmonic stenosis undergoing interventional procedures

BACKGROUND: Beta‐blockade is sometimes used in dogs with pulmonic stenosis with the intent of reducing frequency of ventricular arrhythmias during right heart catheterization. OBJECTIVES: To evaluate if pretreatment with atenolol reduces frequency of ventricular arrhythmias, anesthetist interventions, or shortens procedure time. ANIMALS: Thirty dogs with pulmonic stenosis scheduled for interventional procedures. METHODS: Single center, prospective, randomized, open‐label study. Dogs were randomized to treatment with atenolol or no treatment preoperatively for a minimum of 10 days. Variables recorded included heart rate, arrhythmias and complexity, total procedure time and administration of antiarrhythmic treatment, vasopressors, positive chronotropes, or fluid boluses. RESULTS: Fifteen dogs were enrolled in each group. Dogs receiving atenolol had lower mean heart rates during the procedure (atenolol 100 ± 11 bpm vs untreated 115 ± 19 bpm, P = .01). There were no significant differences between the atenolol and untreated groups in the frequency of ventricular ectopic complexes (535 [6‐5296] vs 553 [79‐2863], P = .9), ventricular couplets (46 [0‐481] vs 29 [3‐121], P = .59), ventricular triplets (20 [0‐265] vs 16 [1‐82], P = .67), ventricular tachycardia (8 [0‐224] vs 8 [1‐118], P = .99), proportion exhibiting R‐on‐T phenomenon (11/15 vs 14/15, P = .33), proportion receiving intraoperative lidocaine (1/15 vs 3/15, P = .6), vasopressors/positive chronotropes (11/15 vs 5/15, P = .06), or fluid boluses (12/15 vs 7/15, P = .13). The procedure time was similar (atenolol 41 [23‐68] min vs untreated 35 [18‐98] min, P = .91). CONCLUSIONS AND CLINICAL IMPORTANCE: No benefit of preoperative atenolol treatment was identified in this small group of dogs

Asymmetric preference formation in willingness to pay estimates in discrete choice models

Individuals when faced with choices amongst a number of alternatives often adopt a variety of processing rules, ranging from simple linear to complex non-linear treatment of each attribute defining the offer of each alternative. In this paper we investigate the presence of asymmetry in preferences to test for reference effects and differential willingness to pay according to whether we are valuing gains or losses. The findings offer clear evidence of an asymmetrical response to increases and decreases in attributes when compared to the corresponding values for a reference alternative, where the degree of asymmetry varies across attributes and population segments

Evaluation of serum cardiac troponin-I concentrations for diagnosis of infective endocarditis in dogs

Abstract Background Infective endocarditis (IE) in dogs is associated with severe disease and a high case fatality rate but often presents with nonspecific clinical signs. Hypothesis/Objectives Serum concentration of cardiac troponin‐I (cTnI) is elevated in dogs with IE and can differentiate dogs with IE from dogs with other diseases with similar clinical features. Concentration of serum cTnI is negatively correlated with survival time in dogs with IE. Animals Seventy‐two client‐owned dogs; 29 with IE, 27 with stage‐B myxomatous mitral valve disease (MMVD), and 16 with immune‐mediated disease (IMD). Methods Retrospective clinical cohort study. Concentration of serum cTnI was measured in all dogs at time of diagnosis. Clinical findings and echocardiographic interpretation were also recorded. Statistical analyses included Kruskal‐Wallis test, pairwise Mann‐Whitney U tests, receiver operator characteristic, and Cox proportional hazards. Results Serum concentration of cTnI was significantly higher in the IE group (0.69 ng/mL [0.03‐80.8]) than in the MMVD (0.05 ng/mL [0.02‐0.11], P 0.625 ng/mL are supportive of IE

Vertical zonation of testate amoebae in the Elatia Mires, northern Greece : palaeoecological evidence for a wetland response to recent climate change or autogenic processes?

The Elatia Mires of northern Greece are unique ecosystems of high conservation value. The mires are climatically marginal and may be sensitive to changing hydroclimate, while northern Greece has experienced a significant increase in aridity since the late twentieth century. To investigate the impact of recent climatic change on the hydrology of the mires, the palaeoecological record was investigated from three near-surface monoliths extracted from two sites. Testate amoebae were analysed as sensitive indicators of hydrology. Results were interpreted using transfer function models to provide quantitative reconstructions of changing water table depth and pH. AMS radiocarbon dates and 210Pb suggest the peats were deposited within the last c. 50 years, but do not allow a secure chronology to be established. Results from all three profiles show a distinct shift towards a more xerophilic community particularly noted by increases in Euglypha species. Transfer function results infer a distinct lowering of water tables in this period. A hydrological response to recent climate change is a tenable hypothesis to explain this change; however other possible explanations include selective test decay, vertical zonation of living amoebae, ombrotrophication and local hydrological change. It is suggested that a peatland response to climatic change is the most probable hypothesis, showing the sensitivity of marginal peatlands to recent climatic change

Social class inequalities in graduates’ labour market outcomes:The role of spatial job opportunities

This paper provides new important evidence on the spatial dimension of social class inequalities in graduates&rsquo; labour market outcomes, an aspect largely overlooked within the existing literature. Using data from the HESA Destinations of Leavers from Higher Education Early and Longitudinal Survey (DLHE) for the 2008/09 graduate cohort and applying multilevel logistic regression models, we investigate whether and the extent to which social class inequalities in graduates&rsquo; occupational outcomes vary depending on the job opportunities in the geographical area where they find employment. By examining different macro-level indicators, we find wider social inequalities by parental social class in areas with fewer opportunities in high professional and managerial occupations and smaller inequalities in areas with more opportunities. Interestingly, this pattern applies only to graduates who moved away from their place of origin. We interpret this finding as the result of selective migration, that is, areas with more opportunities attract the better-qualified graduates irrespective of their social origin. Finally, graduates&rsquo; HE experiences&mdash;in particular, their field of study&mdash;and sector of employment explain most of the social class gap in areas with fewer job opportunities