bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy and safety of early parenteral anticoagulation as a bridge to warfarin after mechanical valve replacement
Authors: Mathew Joseph , Spyropoulos Alex , Yusuf Arif , Vincent Jessica , Eikelboom John , Shestakovska Olga , Fremes Stephen , Noora Joseph , Guo Linrui , Peterson Mark , Pai Menaka , Whitlock Richard 
Published: September 2014

SummaryLimited evidence exists to guide the use of early parenteral anticoagulation following mechanical heart valve replacement (MVR). The purpose of this study was to compare the 30-day rates of thrombotic and bleeding complications for MVR patients receiving therapeutic versus prophylactic dose bridging regimens. In this retrospective cohort study we reviewed anticoagulation management and outcomes of all patients undergoing MVR at five Canadian hospitals between 2003 and 2010. The primary efficacy outcome was thromboembolism (stroke, transient ischaemic attack, systemic embolism or valve thrombosis) and the primary safety outcome was major bleeding at 30-days. Outcomes were compared using a logistic regression model adjusting for propensity score and in a 1:1 propensity matched sample. A total of 1777 patients underwent mechanical valve replacement, of whom 923 received therapeutic dose bridging anticoagulation and 764 received prophylactic dose bridging postoperatively. Sixteen patients (1.8 %) who received therapeutic dose bridging and fifteen patients (2.1 %) who received prophylactic dose bridging experienced the primary efficacy outcome (odds ratio [OR] 0.90; 95 % confidence interval [CI], 0.37 to 2.18, p=0.81). Forty-eight patients (5.4 %) in the therapeutic dosing group and 14 patients (1.9 %) in the prophylactic dosing group experienced the primary safety outcome of major bleeding (OR 3.23; 95 % CI, 1.58 to 6.62; p=0.001). The direction of the effects, their magnitude and significance were maintained in the propensity matched analysis. In conclusion, we found that early after mechanical valve replacement, therapeutic dose bridging was associated with a similar risk of thromboembolic complications, but a 2.5 to 3-fold increased risk of major bleeding compared with prophylactic dose bridging.
Graduated compression stockings to treat acute leg pain associated with proximal DVT
Authors: Shapiro Stan , Ducruet Thierry , Wells Philip , Rodger Marc , Kovacs Michael , Anderson David , Tagalakis Vicky , Morrison David , Solymoss Susan , Miron Marie-José , Yeo Erik , Smith Reginald , Schulman Sam , Kassis Jeannine , Kearon Clive , Chagnon Isabelle , Wong Turnly , Demers Christine , Hanmiah Rajendar , Kaatz Scott , Selby Rita , Rathbun Suman , Desmarais Sylvie , Opatrny Lucie , Ortel Thomas , Galanaud Jean-Philippe , Ginsberg Jeffrey , Kahn Susan 
Published: September 2014

SummaryAcute deep venous thrombosis (DVT) causes leg pain. Elastic compression stockings (ECS) have potential to relieve DVT-related leg pain by diminishing the diameter of distended veins and increasing venous blood flow. It was our objective to determine whether ECS reduce leg pain in patients with acute DVT. We performed a secondary analysis of the SOX Trial, a multicentre randomised placebo controlled trial of active ECS versus placebo ECS to prevent the post-thrombotic syndrome.The study was performed in 24 hospital centres in Canada and the U.S. and included 803 patients with a first episode of acute proximal DVT. Patients were randomised to receive active ECS (knee length, 30–40 mm Hg graduated pressure) or placebo ECS (manufactured to look identical to active ECS, but lacking therapeutic compression). Study outcome was leg pain severity assessed on an 11-point numerical pain rating scale (0, no pain; 10, worst possible pain) at baseline, 14, 30 and 60 days after randomisation. Mean age was 55 years and 60% were male. In active ECS patients (n=409), mean (SD) pain severity at baseline and at 60 days were 5.18 (3.29) and 1.39 (2.19), respectively, and in placebo ECS patients (n=394) were 5.38 (3.29) and 1.13 (1.86), respectively. There were no significant differences in pain scores between groups at any assessment point, and no evidence for subgroup interaction by age, sex or anatomical extent of DVT. Results were similar in an analysis restricted to patients who reported wearing stockings every day. In conclusion, ECS do not reduce leg pain in patients with acute proximal DVT.
Binding of vitronectin and Factor H to Hic contributes to immune evasion of Streptococcus pneumoniae serotype 3
Authors: Kohler Sylvia , Hallström Teresia , Singh Birendra , Riesbeck Kristian , Spartà Giuseppina , Zipfel Peter F. , Hammerschmidt Sven 
Published: September 2014

SummaryStreptococcus pneumoniae serotype 3 strains are highly resistant to opsonophagocytosis due to recruitment of the complement inhibitor Factor H via Hic, a member of the pneumococcal surface protein C (PspC) family. In this study, we demonstrated that Hic also interacts with vitronectin, a fluid-phase regulator involved in haemostasis, angiogenesis, and the terminal complement cascade as well as a component of the extracellular matrix. Blocking of Hic by specific antiserum or genetic deletion significantly reduced pneumococcal binding to soluble and immobilised vitronectin and to Factor H, respectively. In parallel, ectopic expression of Hic on the surface of Lactococcus lactis conferred binding to soluble and immobilised vitronectin as well as Factor H. Molecular analyses with truncated Hic fragments narrowed down the vitronectin-binding site to the central core of Hic (aa 151–201). This vitronectin-binding region is separate from that of Factor H, which binds to the N-terminus of Hic (aa 38–92). Binding of pneumococcal Hic was localised to the C-terminal heparin-binding domain (HBD3) of vitronectin. However, an N-terminal region to HBD3 was further involved in Hic-binding to immobilised vitronectin. Finally, vitronectin bound to Hic was functionally active and inhibited formation of the terminal complement complex. In conclusion, Hic interacts with vitronectin and simultaneously with Factor H, and both human proteins may contribute to colonisation and invasive disease caused by serotype 3 pneumococci.
Improving Quality Measurement for Anticoagulation
Authors: Razouki Zayd , Ozonoff Al , Zhao Shibei , Jasuja Guneet K. , Rose Adam J. 
Published: September 2014

Background—
Among patients receiving warfarin, percent time in therapeutic range (TTR) and international normalized ratio (INR) variability predict adverse events individually. Here, we examined what is added to the prediction of adverse events by using both measures together.

Methods and Results—
We included 40 404 patients anticoagulated for atrial fibrillation, aged 65+, within the Veterans Health Administration. TTR and log-transformed INR variability were calculated for each patient. Our study outcomes were ischemic stroke and major bleeding, defined using International Classification of Diseases-9 codes. We estimated the hazard ratios (HRs) for the study outcomes using 3 nested Cox regression models, including (1) TTR or log INR variability separately; (2) TTR and log INR variability together; and (3) both predictors together plus an interaction term. We divided TTR into 3 categories (high, >70%; moderate, 50% to 70%; low, <50%) and log INR variability into 2 categories (stable and unstable). The reference groups high TTR and stable anticoagulation each denote good control.

Higher log INR variability (ie, unstable control) predicted ischemic stroke (HR=1.45,
P
<0.001) and major bleeding (HR=1.57,
P
<0.001) independently, regardless of TTR levels. Our model with interaction terms showed that High log INR variability predicted a significantly higher risk for ischemic stroke and major bleeding compared with low log INR variability, at moderate TTR levels (HR= 1.27 and HR=1.29, respectively) and at high TTR levels (HR=1.55 and HR=1.56, respectively), but not at low TTR levels.

Conclusions—
Unstable anticoagulation predicts warfarin adverse effects independent of TTR. Moreover, knowledge about anticoagulation stability further stratifies the risk for adverse events at given levels of TTR.
Impact of System and Physician Factors on the Detection of Obstructive Coronary Disease With Diagnostic Angiography in Stable Ischemic Heart Disease
Authors: Wijeysundera Harindra C. , Qiu Feng , Bennell Maria C. , Natarajan Madhu K. , Cantor Warren J. , Smith Stuart , Kingsbury Kori J. , Ko Dennis T. 
Published: September 2014

Background—
Wide variation exists in the detection rate of obstructive coronary artery disease (CAD) with elective coronary angiography for suspected stable ischemic heart disease. We sought to understand the incremental impact of nonclinical factors on this variation.

Methods and Results—

We included all patients who underwent coronary angiography for possible suspected stable ischemic heart disease, from October 1, 2008, to September 30, 2011, in Ontario, Canada. Nonclinical factors of interest included physician self-referral for angiography, the physician type (invasive or interventional), and hospital type. Hospitals were categorized into diagnostic angiogram only centers, stand-alone percutaneous coronary intervention centers, or full service centers with coronary artery bypass surgery available. Multivariable hierarchical logistic models were developed to identify system and physician-level predictors of obstructive CAD, after adjustment for patient factors. Our cohort consisted of 60 986 patients, of whom 31 726 had obstructive CAD (52.0%), with significant range across hospitals from 37.3% to 69.2%. Fewer self-referral patients (49.8%) had obstructive CAD compared with nonself-referral patients (53.5%), with an odds ratio of 0.89 (95% confidence interval, 0.86–0.93;
P
<0.001). Angiograms performed by invasive physicians had a lower likelihood of obstructive CAD compared with those by interventional physicians (48.2% versus 56.9%; odds ratio, 0.85; 95% confidence interval, 0.81–0.90;
P
<0.001). Fewer angiograms at diagnostic only centers showed obstructive CAD (42.0%) compared with full service centers (55.1%; odds ratio, 0.62; 95% confidence interval, 0.39–0.98;
P
=0.04). Nonclinical factors accounted for 23.8% of the variation between hospitals.

Conclusions—
Physician and system factors are important predictors of obstructive CAD with coronary angiography.
Effects of Sapropterin on Endothelium-Dependent Vasodilation in Patients With CADASIL
Authors: De Maria Renata , Campolo Jonica , Frontali Marina , Taroni Franco , Federico Antonio , Inzitari Domenico , Tavani Alessandra , Romano Silvia , Puca Emanuele , Orzi Francesco , Francia Ada , Mariotti Caterina , Tomasello Chiara , Dotti Maria Teresa , Stromillo Maria Laura , Pantoni Leonardo , Pescini Francesca , Valenti Raffaella , Pelucchi Claudio , Parolini Marina , Parodi Oberdan , Sedda Valentina , Spagnolo Elisabetta , De Stefano Nicola 
Published: September 2014

Background and Purpose—

Cerebral autosomal–dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a rare autosomal dominant disorder caused by
NOTCH3
mutations, is characterized by vascular smooth muscle and endothelial cells abnormalities, altered vasoreactivity, and recurrent lacunar infarcts. Vasomotor function may represent a key factor for disease progression. Tetrahydrobiopterin, essential cofactor for nitric oxide synthesis in endothelial cells, ameliorates endothelial function. We assessed whether supplementation with sapropterin, a synthetic tetrahydrobiopterin analog, improves endothelium-dependent vasodilation in CADASIL patients.

Methods—
In a 24-month, multicenter randomized, double-blind, placebo-controlled trial, CADASIL patients aged 30 to 65 years were randomly assigned to receive placebo or sapropterin 200 to 400 mg BID. The primary end point was change in the reactive hyperemia index by peripheral arterial tonometry at 24 months. We also assessed the safety and tolerability of sapropterin. Analysis was done by intention-to-treat.

Results—
The intention-to-treat population included 61 patients. We found no significant difference between sapropterin (n=32) and placebo (n=29) in the primary end point (mean difference in reactive hyperemia index by peripheral arterial tonometry changes 0.19 [95% confidence interval, −0.18, 0.56]). Reactive hyperemia index by peripheral arterial tonometry increased after 24 months in 37% of patients on sapropterin and in 28% on placebo; however, after adjustment for age, sex, and clinical characteristics, improvement was not associated with treatment arm. The proportion of patients with adverse events was similar on sapropterin and on placebo (50% versus 48.3%); serious adverse events occurred in 6.3% versus 13.8%, respectively.

Conclusions—
Sapropterin was safe and well-tolerated at the average dose of 5 mg/kg/day, but did not affect endothelium-dependent vasodilation in CADASIL patients.

Clinical Trial Registration—

URL:
https://www.clinicaltrialsregister.eu
. Unique identifier: 2007-004370-55.
Efficacy of Antidepressants in Animal Models of Ischemic Stroke
Authors: McCann Sarah K. , Irvine Cadi , Mead Gillian E. , Sena Emily S. , Currie Gillian L. , Egan Kieren E. , Macleod Malcolm R. , Howells David W. 
Published: September 2014

Background and Purpose—
Poststroke depression is a prevalent complication of stroke with unclear pathogenesis. The benefits of antidepressants in this context and their effects on stroke recovery other than effects on mood are not clearly defined, with some studies suggesting efficacy in improving functional outcome in both depressed and nondepressed stroke patients. We have analyzed the preclinical animal data on antidepressant treatment in focal cerebral ischemia, modeled±depression, to help inform clinical trial design.

Methods—
We performed a systematic review and meta-analysis of data from experiments testing the efficacy of antidepressants versus no treatment to reduce infarct volume or improve neurobehavioral or neurogenesis outcomes in animal models of stroke. We used random-effects metaregression to test the impact of study quality and design characteristics and used trim and fill to assess publication bias.

Results—
We identified 44 publications describing the effects of 22 antidepressant drugs. The median quality checklist score was 5 of a possible 10 (interquartile range, 4–7). Overall, antidepressants reduced infarct volume by 27.3% (95% confidence interval, 20.7%–33.8%) and improved neurobehavioral outcomes by 53.7% (46.4%–61.1%). There was little evidence for an effect of selective serotonin reuptake inhibitors on infarct volume. For neurobehavioral outcomes there was evidence of publication bias. Selective serotonin reuptake inhibitors were the most frequently studied antidepressant subtype and improved neurobehavioral outcome by 51.8% (38.6%–64.9%) and increased neurogenesis by 2.2 SD (1.3–3.0).

Conclusions—
In line with current clinical data and despite some limitations, antidepressant treatments seem to improve infarct volume and neurobehavioral outcome in animal models of ischemic stroke.
Variability of the Australian Monsoon and Precipitation Trends at Darwin
Authors: Evans Stuart , Marchand Roger , Ackerman Thomas 
Published: September 2014

Abstract
An atmospheric classification for northwestern Australia is used to define periods of monsoon activity and investigate the interannual and intraseasonal variability of the Australian monsoon, as well as long-term precipitation trends at Darwin. The classification creates a time series of atmospheric states, which two correspond to the active monsoon and the monsoon break. Occurrence of these states is used to define onset, retreat, seasonal intensity, and individual active periods within seasons. The authors demonstrate the quality of their method by showing it consistently identifies extended periods of precipitation as part of the monsoon season and recreates well-known relationships between Australian monsoon onset, intensity, and ENSO. The authors also find that onset and seasonal intensity are significantly correlated with ENSO as early as July.
Previous studies have investigated the role of the Madden–Julian oscillation (MJO) during the monsoon by studying the frequency and duration of active periods, but these studies disagree on whether the MJO creates a characteristic period or duration. The authors use their metrics of monsoon activity and the Wheeler–Hendon MJO index to examine the timing of active periods relative to the phase of the MJO. It is shown that active periods preferentially begin during MJO phases 3 and 4, as the convective anomaly approaches Darwin, and end during phases 7 and 8, as the anomaly departs Darwin. Finally, the causes of the multidecadal positive precipitation trend at Darwin over the last few decades are investigated. It is found that an increase in the number of days classified as active, rather than changes in the daily rainfall rate during active monsoon periods, is responsible.
Understanding the Anthropogenically Forced Change of Equatorial Pacific Trade Winds in Coupled Climate Models*
Authors: Xiang Baoqiang , Wang Bin , Li Juan , Zhao Ming , Lee June-Yi 
Published: September 2014

Abstract
Understanding the change of equatorial Pacific trade winds is pivotal for understanding the global mean temperature change and the El Niño–Southern Oscillation (ENSO) property change. The weakening of the Walker circulation due to anthropogenic greenhouse gas (GHG) forcing was suggested as one of the most robust phenomena in current climate models by examining zonal sea level pressure gradient over the tropical Pacific. This study explores another component of the Walker circulation change focusing on equatorial Pacific trade wind change. Model sensitivity experiments demonstrate that the direct/fast response due to GHG forcing is to increase the trade winds, especially over the equatorial central-western Pacific (ECWP) (5°S–5°N, 140°E–150°W), while the indirect/slow response associated with sea surface temperature (SST) warming weakens the trade winds.
Further, analysis of the results from 19 models in phase 5 of the Coupled Model Intercomparison Project (CMIP5) and the Parallel Ocean Program (POP)–Ocean Atmosphere Sea Ice Soil (OASIS)–ECHAM model (POEM) shows that the projected weakening of the trades is robust only in the equatorial eastern Pacific (EEP) ( 5°S–5°N, 150°–80°W), but highly uncertain over the ECWP with 9 out of 19 CMIP5 models producing intensified trades. The prominent and robust weakening of EEP trades is suggested to be mainly driven by a top-down mechanism: the mean vertical advection of more upper-tropospheric warming downward to generate a cyclonic circulation anomaly in the southeast tropical Pacific. In the ECWP, the large intermodel spread is primarily linked to model diversity in simulating the relative warming of the equatorial Pacific versus the tropical mean sea surface temperature. The possible root causes of the uncertainty for the trade wind change are also discussed.
Observations of Internal Gravity Waves by Argo Floats
Authors: Hennon Tyler D. , Riser Stephen C. , Alford Matthew H. 
Published: September 2014

AbstractThis study examines the global variability of the internal wave field near a depth of 1000 m using data from a set of 194 Argo floats equipped with Iridium communications, capable of measuring hourly temperature and pressure during the park phase of their 10-day cycles. These data have been used to estimate vertical isotherm displacements at hourly intervals, yielding a global measure of the heaving due to internal gravity waves. The displacement results have been employed to examine the global variability of these waves and how the displacement power spectrum compares to the canonical Garrett–Munk spectrum. Using the data, the authors find correlations between internal wave intensity and seafloor roughness, proximity to the seafloor, and the magnitude of the local barotropic velocity. The measurements also show large seamount-trapped waves at high latitudes and coastally trapped subinertial waves. These observations provide a rough global census of the nature of these waves that can ultimately be used in studies of ocean mixing.
Estimation of Winds from GPS Radio Occultations
Authors: Verkhoglyadova Olga P. , Leroy Stephen S. , Ao Chi O. 
Published: September 2014

AbstractGPS radio occultations (RO) offer the possibility to map winds in the upper troposphere and lower stratosphere (UTLS) region because geopotential height is the independent coordinate of retrieval. Most other sounders do not offer this possibility because their independent coordinate of retrieval is pressure. To estimate the precision with which GPS radio occultation data can map winds, dry pressure profiles are simulated from the Interim European Centre for Medium-Range Weather Forecasts Re-Analysis (ERA-Interim) at the actual locations of the Challenging Minisatellite Payload (CHAMP) and the Constellation Observing System for Meteorology, Ionosphere and Climate (COSMIC) soundings for the year 2007. Monthly wind maps were created by using Bayesian interpolation on subsampled ERA-Interim data in 3–5-day bins and subsequent averaging over a month. Mapping winds in this approach requires that 1) geostrophy approximates winds; 2) dry pressure approximates pressure in the UTLS; and 3) geopotential height can be mapped accurately given sparse, nonuniform distributions of data. This study found that, under these conditions, it is possible to map monthly winds near the tropopause with an accuracy of 5.6 m s−1 with CHAMP alone and 4.5 m s−1 with COSMIC alone. The dominant contributors to uncertainty are undersampling of the atmosphere and ageostrophy, particularly at the leading and trailing edges of the subtropical jet. The former is reduced with increased density of GPS RO soundings. The latter cannot be reduced even after iteration for balanced winds. Nevertheless, it is still possible to capture the general wind pattern and to determine the position of the subtropical jet despite the uncertainty in its magnitude. COSMIC radio occultation measurements from 2006 through 2011 were used to estimate monthly geostrophic winds maps in UTLS. The resultant wind dataset is posted online.
Assimilation of Lightning Data Using a Nudging Method Involving Low-Level Warming
Authors: Marchand Max R. , Fuelberg Henry E. 
Published: September 2014

Abstract
This study presents a new method for assimilating lightning data into numerical models that is suitable at convection-permitting scales. The authors utilized data from the Earth Networks Total Lightning Network at 9-km grid spacing to mimic the resolution of the Geostationary Lightning Mapper (GLM) that will be on the Geostationary Operational Environmental Satellite-R (GOES-R). The assimilation procedure utilizes the numerical Weather Research and Forecasting (WRF) Model. The method (denoted MU) warms the most unstable low levels of the atmosphere at locations where lightning was observed but deep convection was not simulated based on the absence of graupel. Simulation results are compared with those from a control simulation and a simulation employing the lightning assimilation method developed by Fierro et al. (denoted FO) that increases water vapor according to a nudging function that depends on the observed flash rate and simulated graupel mixing ratio. Results are presented for three severe storm days during 2011 and compared with hourly NCEP stage-IV precipitation observations. Compared to control simulations, both the MU and FO assimilation methods produce improved simulated precipitation fields during the assimilation period and a short time afterward based on subjective comparisons and objective statistical scores (~0.1, or 50%, improvement of equitable threat scores). The MU generally performs better at simulating isolated thunderstorms and other weakly forced deep convection, while FO performs better for the case having strong synoptic forcing. Results show that the newly developed MU method is a viable alternative to the FO method, exhibiting utility in producing thunderstorms where observed, and providing improved analyses at low computational cost.