bluuebunny/crossref_metadata_2025 huggingface dataset:
Long-Term Follow Up with Regard to Potential Immunogenicity: Clinical Experience with NovoSeven® (Recombinant Factor VIla)
Authors: Nicolaisen Else Marie
Published: April 2009

Twenty-eight patients were followed up for potential specific antibody formation after repeated use of recombinant factor VIla (rFVIIa). The population included 27 patients with congenital bleeding disorders and 1 nonhemophiliac with an FVIII inhibitor. From 5 to 77 bleeding episodes were treated during a follow-up period of at least 5 months. None of these repeatedly treated patients showed signs of antibody formation against FV∏ or foreign protein that could be related to the treatment.
Dosing and Monitoring NovoSeven® Treatment
Authors: Hedner Ulla
Published: April 2009

The concept of using factor VIla (FVIIa) to induce hemostasis in hemophilia is new and takes advantage of the normal tissue factor/FVII-dependent coagulation pathway which is enhanced by the administration of extra exogenous recombinant FVIIa. Since this is a pharmacological treatment and not a simple substitution therapy the current dosis recommendations are based on preclinical data (in vitro and in animals) as well as on clinical experience. It is concluded that the initial dose should be high enough to maintain a plasma level of FVII-coagulant activity (FVII:C) at > 6 U/ml for several hours corresponding roughly to a dose of 90-120 μg/kg.
Major Surgery in Haemophilic Patients with Inhibitors Using Recombinant Factor VIla
Authors: Ingerslev J. , Freidman D. , Gastineau D. , Gilchrist G. , Johnsson H. , Lucas G. , McPherson J. , Preston E. , Scheibel E. , Shuman M.
Published: April 2009

In the haemophilic patient, development of antibodies that inhibit the function of the missing coagulation factor causes several delicate problems. Most importantly, antibodies will block the function of the specific coagulation factor, and often the antibody activity is so fierce that effective substitution therapy is outruled. In consequence, alternative measures must be adopted to control bleeding. Amongst those most commonly employed, like factor IX concentrates, activated prothrombin complex concentrates, and factor VIII of porcine origin, a new recombinant activated factor VII molecule has been evaluated clinically for some years with promising results. The aim of the present paper was to present a series of patients suffering from haemophilia A or B in whom inhibitors have complicated the clinical picture, and in whom a surgical procedure was indicated. As part of a compassionate use program devised by the producer of this genetically engineered factor VIla, 12 patients underwent life-saving or essential surgery where the recombinant factor VIla product was used to promote haemostasis in 13 surgical procedures. Due to a short in vivo half-life of activated factor VIla, frequent administration was scheduled, injecting factor VIla every 2-3 h for up to 2 days after which dosage intervals were prolonged. In one case, a global evaluation of the end treatment result was not reported, but in all of the other 12 cases the end result were considered excellent (n = 11) or efficient (n = 1). In none of the cases was other types of coagulation factor treatment modalities necessary. In conclusion, recombinant factor VIla seems a tempting alternative to traditional treatment of the haemophilic patient with inhibitors, in whom surgery is called for. With other types of haemostatic agents, surgery in haemophilic inhibitor patients has only been studied rarely, and operations have generally been restricted to life-threatening situations.
Recombinant Factor VIla (NovoSeven®) in the Treatment of Internal Bleeding in Patients with Factor VIM and IX Inhibitors
Authors: Lusher Jeanne M.
Published: April 2009

Recombinant factor VIla (NovoSeven®) was used on a compassionate use basis to treat 51 episodes of internal bleeding in 43 patients. All had become refractory to (or were not candidates for) other therapeutic agents. 26 of the 43 patients had hemophilia A and FVIII inhibitor antibodies, 13 had acquired FVIII inhibitors, 2 had hemophilia B and FIX inhibitors, and 2 had other coagulopathies, of 50 episodes of internal bleeding evaluated 76% had an excellent or effective response to rFVIIa. The average dosage given was 84 μg/kg; the median number of doses given was 38. rFVIIa appears to be a very valuable addition to one’s therapeutic armamentarium for treating serious bleeding episodes in inhibitor patients.
NovoSeven® (Recombinant Factor VIla) in Central Nervous System Bleeds
Authors: Rice K.M. , Savidge G.F.
Published: April 2009

Data is presented from two compassionate-use clinical trials using recombinant factor VIla (rFVIIa) to treat central nervous system haemorrhage in 18 haemophilia A and B patients with inhibitors, and in 3 patients with FVII deficiency. Prior to rFVIIa treatment 78% of the haemophilia patients had inhibitor titres greater than 10 Bethesda units/ml. Sixty-two percent of the bleeding episodes were treated with a mean dose of 80-100 μg/kg of rFVIIa administered repeatedly until cessation of bleeding. The overall efficacy was 84% with only one fatality and there were no major adverse events or laboratory indicators of disseminated intravascular coagulation.
Recombinant Factor VIla in Joint and Muscle Bleeding Episodes
Authors: Mølskov Bech R.
Published: April 2009

Recombinant factor Vila (rFVIIa) improves haemostasis and eliminates the risk of transmission of blood-borne infection in haemophilia patients with inhibitors, acquired inhibitors to factor VIII or IX or FVII deficiency. rFVIIa has been available on a compassionate use basis since 1988 and has been administered to 111 patients for a total of 494 joint and muscle bleeding episodes. Seventy-nine percent of joint and 65% of muscle bleeding episodes were evaluated by the investigator as having an excellent/effective response. rFVIIa is also an effective treatment for joint and muscle bleeding episodes in patients undergoing immune tolerance regimens and does not affect the inhibitor titre level.
Thrombelastgram as a Hemostatic Monitor during Recombinant Factor VIla Treatment in Hemophilia A Patients with Inhibitor to Factor VIII
Authors: Yoshioka A. , Nishio K. , Shima M.
Published: April 2009

Thrombelastgram (TEG) is an old but automated instrument that demonstrates changes occurring during blood coagulation and fibrinolysis. TEG was evaluated to be better than activated partial thromboplastin time (APTT) as a monitor of hemostatic effects when using recombinant factor VIla (65-80 μg/kg) in 3 hemophilia A patients with a high titer of factor VIII inhibitors. TEG was more suitable than APTT, because r, r+k and ma values of TEG were normalized at least for 4 h after the infusion, whereas APTT was variably shortened and was not always maintained at a normal level for 4 h.
Use of Recombinant Factor VIla (NovoSeven®) in the Treatment of Two Patients with Type III von Willebrand’s Disease and an inhibitor against von Willebrand Factor
Authors: Ciavarella N. , Schiavoni M. , Valenzano E. , Mangini F. , Inchingolo F.
Published: April 2009

Two siblings affected by type III von Willebrand’s disease with precipitating alloantibodies against von Willebrand’s factor (vWF) and not susceptible to treatment with factor VIII/ vWF concentrates received recombinant activated factor VII for oral surgery. This therapy, combined with antifibrinolytic drugs and local application of fibrin glue, seems to be effective and safe. It may be considered a promising approach to the management of this rare condition.
Treatment of Factor VII Deficiency with Recombinant Factor VIla
Authors: Bauer Kenneth A.
Published: April 2009

Factor VII deficiency is a relatively infrequent hereditary bleeding disorder. Recombinant factor VIla has been used to treat patients with factor VII deficiency with bleeding episodes or undergoing surgery. The drug has shown a high efficacy rate and will provide factor VH-deficient patients with a therapeutic agent that is not derived from human plasma.
Clinical Experience with Recombinant Factor VIla in Patients with Thrombocytopenia
Authors: Kristensen Jörgen , Killander Andreas , Hippe Erik , Helleberg Carsten , Ellegård Jörgen , Holm Mette , Kutti Jack , Mellqvist Ulf-Henrik , Johansson Jan Erik , Glazer Steven , Hedner Ulla
Published: April 2009

Platelets play a central role in primary hemostasis. The role of the coagulation mechanism during early stages of hemostasis is less clear, although increasing evidence is emerging indicating the ultimate importance of the factor VII (FVII)-tissue factor-dependent coagulation system in providing the first thrombin molecules necessary for the platelet activation to occur. Supporting this, early fibrin formation has been reported to occur within the bleeding time wound and infusion of recombinant FVIIa (rFIIa) has been shown to shorten the bleeding time in rabbits. We have investigated whether infusion of rFVIIa would enhance fibrin formation in bleeding time wounds in patients with thrombocytopenia as reflected by a shortening of the bleeding time. A reduction of the bleeding time was found in 55/105 cases (52%). The decrease was significantly more pronounced when the platelet count exceeded 20 × 109/l. With the exception of an anaphylactoid reaction in 1 patient, no major adverse reactions related to the study drug were observed. Nine infusions of rFVIIa were given to 8 thrombocytopenic patients with overt bleeding. One patient received two infusions. Bleeding decreased in all patients and stopped in 6 patients.
Low-Molecular-Weight Heparins and New Strategies for the Treatment of Patients with Established Venous Thrombosis
Authors: Baglin T.P.
Published: April 2009

Unfractionated heparin is the commonest treatment for established venous thromboembolism. While this treatment undoubtedly reduces mortality and morbidity there are problems associated with its use. It does not always prevent thrombus propagation or embolisation, the low bioavailability results in a frequent failure to achieve therapeutic heparin levels in vivo and the variable sensitivity of the partial thromboplastin time to the heparin effect may result in inappropriate heparin dosage. The low-molecular-weight heparins have high predictable bioavailability and can be administered as weight-calculated fixed-dose regimens for the treatment of established venous thromboembolism. While statistically significant clinical results are awaited, there is increasing evidence for the superior benefit-risk ratios for these agents compared to unfractionated heparin. In routine practice, the frequent failure to achieve a therapeutic intensity of anticoagulation is currently the main reason for adopting low-molecular-weight heparins for first-line treatment of venous thromboembolism. Cost analysis studies based on total health care costs may support the use of these drugs, because savings from the abolishment of laboratory monitoring, improved clinical outcome and shorter in-patient stay may prove treatment with low-molecular weight heparin to be more cost-effective than treatment with unfractionated heparin.
Prevention of Venous Thromboembolic Risk in Non-Surgical Patients
Authors: Bergmann Jean-François , Elkharrat David
Published: April 2009

The risk of deep-vein thrombosis in hospitalized medical patients varies considerably among diseases and should be systematically assessed as a function of the presence of different risk factors. The need for drug prophylaxis of thromboembolic risk in patients at moderate or high risk of thrombosis is now recommended. In such cases, only standard or low-molecular-weight heparins have been evaluated in controlled trials. The efficacy of heparin prophylaxis has been demonstrated in hospitalized cardiac patients following myocardial infarction, in neurological patients with paralysis of one or both lower limbs, and in intensive-care patients or in those with a serious medical condition, particularly if they have a history of deep-vein thrombosis. The choice between the different heparins, their dosages and treatment durations, and the possible indication for prophylaxis in patients at low thrombotic risk should be evaluated in controlled trials.
Low-Molecular-Weight Heparins: An Overview of their Pharmacodynamics, Pharmacokinetics and Metabolism in Humans
Authors: Frydman Armand
Published: April 2009

Low-molecular-weight heparins (LMWHs) comprise a group in the class of antithrombotic medications, a class headed by unfractionated heparin (UFH). The LMWHs, with mean molecular weights of 4.0-6.0 kD, differ in their individual manufacturing processes, the distribution of their fragment molecular weights, their in vitro potency (anti-Xa, antithrombin and anticoagulant activities) and, consequently, in their biodynamic patterns, recommended dose regimen, and efficacy/safety ratio. Their drug disposition profiles have been evaluated using two significant markers of their pharmacodynamic activity, namely anti-Xa and anti-IIa activities. Since they are mainly administered subcutaneously, then compared to UFH, they are almost completely absorbed (F > 90%) and, in contrast to UFH, those for which data are available in the literature exhibit linear pharmacokinetics with proportionality between anti-Xa (and anti-IIa in some cases) plasma concentration and dose, and stationary distribution volume and clearance processes when the dosage is increased. Their distribution volume is close to the blood volume, they are partially metabolized by desulphatation and depolymerization, but urinary excretion of anti-Xa activity for enoxaparin, dalteparin and nadroparin, all given at doses for prevention of venous thrombosis, is between 5 and 10% of the injected dose. However, these LMWHs differ in the extent of their non-renal clearance, resulting in different apparent elimination half-life values and relative apparent bioavailability. When considering certain at-risk situations, using doses for preventing thromboembolism, the LMWHs do not significantly cross the placenta of pregnant women and their excretion profiles are only slightly altered in severe (endogenous creatinine clearance less than 15 ml/min) renal disease patients when given at doses recommended for prevention of venous thromboembolism. Because of the differences among LMWHs, the clinical profile of a given LMWH cannot be extrapolated to another one or generalized to the whole LMWH family.
The Venous Thrombotic Risk in Non-Surgical Patients: Epidemiological Data and Efficacy/Safety Profile of a Low-Molecular-Weight Heparin (Enoxaparin)
Authors: Lechler E. , Schramm W. , Flosbach C.W.
Published: April 2009

In a multicentre, randomized, double-blind controlled trial comparing the low-molecular-weight heparin enoxaparin (40 mg) with a standard unfractionated heparin (Ca-heparin, 3 × 5,000 U) in deep-vein thrombosis prophylaxis in a high-risk group of 959 hospitalized medical patients, enoxaparin was at least as efficacious as standard heparin, with fewer adverse events.
Mechanisms, Markers and Management of Hypercoagulable States
Authors: Mannucci Pier Mannuccio , Tripodi Armando
Published: April 2009

Information on hypercoagulability can be achieved through the measurement of pep-tides that are generated when zymogens are activated, of the active enzymes, or of the complexes that form in the circulation when enzymes are inactivated by their plasmatic inhibitors. These assay methods have dramatically improved our understanding of the mechanisms which regulate coagulation in health and disease. However, their choice and use as predictors of thrombotic events and to monitor anticoagulant treatment still need to be defined in prospective clinical trials.
Consequences Of Transcellular Biosynthesis Of Leukotriene C4 On Organ Function
Authors: Maclouf Jacques , Sala Angelo , Rossoni Giuseppe , Berti Ferruccio , Muller-Peddinghaus Reiner , Folco Giancarlo
Published: April 2009

Formation of eicosanoids is a special mode of cell communication whereby production of eicosanoids by mixed cell populations differs from that expected from each individual cell. Transcellular biosynthesis of leukotriene C4 occurs via transfer of the reactive intermediate leukotriene A4 from neutrophils to vicinal acceptor cells devoid of 5-lipoxygenase activity such as platelets or vascular cells. Evidence for the in vivo relevance of transcellular eicosanoid metabolism results from experiments using the isolated beating rabbit heart perfused with activated neutrophils. The resultant leukotriene C4 synthesis is timely related to the pressor response of the coronary arteries and inflammatory damage of the heart by edema formation and neutrophil infiltration into the organ. Blockade of leukotriene C4 synthesis by 5-lipoxygenase inhibitors or leukotriene C4 actions by respective receptor antagonists facilitated significant protective effects. Further confirmation of the potential role of LTC4 in myocardial ischemia comes from in vivo studies in the rabbit.
Injury Models Of The Vascular Endothelium: Apoptosis And Loss Of Thromboresistance Induced By A Viral Protein
Authors: Eldor A. , Sela-Donenfeld D. , Korner M. , Pick M. , Resnick-Roguel N. , Panet A.
Published: April 2009

Endothelial injury caused by viruses usually involves viral replication or transformation. We report a novel mechanism of endothelial damage by a toxic viral protein. We have isolated a new retrovirus from hemangiosarcomas which appeared among layer hens. The isolated avian hemangiosarcoma virus (AHV) is capable of inducing hemangiomas in hens in-vivo and causes a cytopathic effect (CPE) and loss of thromboresistance in cultured bovine aortic endothelial cells (BAEC). These effects do not require viral replication and can be induced by purified AHV envelope glycoprotein (gp85). AHV causes CPE in BAEC through a typical programmed cell death (apoptosis). Quiescent G0/G1-BAEC are much more sensitive to AHV induced apoptosis than actively dividing cells. These experiments demonstrate the capacity of viral proteins to affect the integrity and functionality of vascular endothelial cells.
Dietary Fatty Acids In Athero-Thrombogenesis: Influence Of Palm Oil Ingestion
Authors: de Bosch Norma B , Bosch Virgilio , Apitz Rafael
Published: April 2009

Dietary experiments, performed in metabolic wards, gave rise to predictive regression equations relating changes of plasma cholesterol concentration to the intake of fatty acids of the diet. It has been established that polyunsaturated fatty acids diminish and most saturated fatty acids increase plasma cholesterol concentration. This information led to expect that dietary use of palm oil may induce an unfavorable plasma lipoprotein profile. This has not been the case as shown in various dietary experiments. The reasons for this discrepancy is discussed. The influence of palm oil enriched diets on prothrombotic variables show that platelets are not affected in their function during prolonged dietary intervention. It is important to continue research on the effects of palm oil based diet on plasma fibrinogen, factor VII. There is still discordant information in this field.
Which experimental model to choose to study arterial thrombosis and evaluate potentially useful therapeutics?
Authors: Andre Patrick , Bal dit Sollier Claire , Bonneau Michel , Pignaud George , Hainaud Patricia , Azzam Kalid , Drouet Ludovic
Published: April 2009

The use of experimental models of arterial thrombosis both in vivo and ex vivo in animals and ex vivo in humans is an obligatory step for the understanding of mechanisms involved in thrombogenesis as well as in the evaluation of anti-thrombotic therapeutics. Arterial thrombogenesis is a complex phenomenon which involves multiple systems, mechanisms and parameters. Therefore studies of thrombogenesis from a pathological as well as a therapeutic point are necessary for understanding this problem in its entirety. For these reasons, it is necessary to use models as representative as possible of the human pathological condition. Besides these theoretical requirements, practical needs have also to be fulfilled (accessibility of the models, adaptation to the type of the technique to different animal model and/or of the size of the animal to the amount of molecule available, cost...) which necessary lead to some promises. In this review we have tried to underline the criteria for the choice, characteristics, advantages and disadvantages of the major models commonly accepted and used, in such a form that the reader who may not be an expert in the field would be led either to a choice of a particular model for a specific purpose or to appreciate a paper or a report based on an experimental model of arterial thrombosis. In vitro models of arterial thrombosis are so far removed from reality and due to their nature can generate so much artifacts that we have omitted their discussion from this paper.
Modulating Platelet Function With Selective Thrombin Inhibitors
Authors: Verstraete M.
Published: April 2009

In addition to its pivotal role in blood coagulation, thrombin is one of the most important agonists for platelet recruitment and aggregation. Thrombin inhibitors impede thrombin-induced platelet aggregation but have no effect on aggregation induced by other agonists. A review is presented of selective thrombin inhibitors now in clinical investigation, some of which are also orally active.
New thoughts on strategies for modulating platelet function through the inhibition of surface receptors
Authors: Nurden Alan T
Published: April 2009

Platelets play a key role in arterial thrombosis. Inhibition of platelet function forms an essential part of anti-thrombotic therapy. Although aspirin is a cost-effective drug which offers considerable scope in the prevention of arterial thrombosis, it only inhibits part of the platelet activation process. Much recent progress has concerned the inhibition of surface receptors of platelets. Ticlopidine and clopidogrel specifically interfere with the ADP-induced activation pathway. Inhibitors of GP IIb-IIIa complexes, including c7E3, block the final step of the platelet aggregation process as used by all physiologic agonists and are proving powerful therapeutic agents. This review looks at these and future advances in the construction of therapeutic strategies aimed at combatting arterial thrombosis.
Influence Of Hypoxia And Hypoxia-Reoxygenation On Endothelial P-Selectin Expression
Authors: Closse Christèle , Seigneur Martine , Renard Martine , Pruvost Annie , Dumain Patrice , Belloc Francis , Boisseau Michel René
Published: April 2009

P-selectin is an endothelial adhesion molecule involved in the initial step of the neutrophil recruitment. We investigated the effect of hypoxia (95% N2, 5% CO2) and of hypoxia-reoxygenation (95% air, 5% CO2) on the expression of P-selectin by human umbilical vein endothelial cells (HUVEC). P-selectin expression was detected by immunolabelling and quantified by flow cytometric analysis. Our data indicate that hypoxia induces an increase in P-selectin expression with a maximum reached after 90 minutes. A hypoxic exposure of 90 minutes results in a highly significant increase compared to normoxia (p < 0.001, n=13). Furthermore, when a reoxygenation period follows 90 minutes of hypoxia, the initially elevated levels of P-selectin are dramatically enhanced with a maximum obtained after 60 minutes of reoxygenation.
Effect Of Buflomedil On The Neutrophil-Endothelial Cell Interaction Under Inflammatory And Hypoxia Conditions
Authors: Boisseau M.R. , Pruvost A. , Renard M. , Closse C. , Belloc F. , Seigneur M. , Maurel A.
Published: April 2009

In hypoxia/ischaemia and ischaemia/reperfusion, human neurophils are likely to play an important role in the development of endothehal cell damage in the microcirculation. Buflomedil hypochloride improves the capillary perfusion in such related situations, evoking a possible effect upon neutrophils. Using in vitro models of cell adhesion, buflomedil decreased 100% of histamin related neutrophil adhesion (flow sytem) and partially inhibited adhesion after IL-1–4 hours (flow and stable systems). Hypoxia induced neutrophil adhesion (4 hours) was also reduced by buflomedil, which decreased the expression of P-selectin at the surface of endothehal cells. As adenosin (NECA) exhibited the same results in hypoxia and theophylline inhibited them, such results support an action of buflomedil presumably via the A2 receptor.
New Antithrombotic Agents For The Prevention And Treatment Of Deep Vein Thrombosis
Authors: Boneu B.
Published: April 2009

Besides low molecular weight heparins (LMWHs) a number of new antithrombotic agents have been evaluated mainly in the prevention of deep vein thrombosis (DVT) and, to a lesser extent, in the treatment of established DVT. They include the Pentasaccharide, a synthetic ultra LMWH, Dermatan Sulphate, a glycosaminoglycan which activates heparin cofactor II, Orgaran, a mixture of Heparan and of Dermatan Sulphate, Hirulog and Hirudin, two direct thrombin inhibitors. The efficacy and safety of these compounds have been studied in comparison with a placebo or with unfractionated heparin but not with LMWH which is considered as a gold standard for these clinical indications. It is thus difficult at present to appreciate the advantages of these new antithrombotic agents over conventional LMWH therapy.
Neutralization of DHG, a New Depolymerized Holothurian Glycosaminoglycan, by Protamine Sulfate and Platelet Factor 4
Authors: Sasaki Eiji , Minamiguchi Kazuhisa , Kitazato Keiko T. , Nagase Hideki , Kitazato Kenji
Published: April 2009

The neutralization of depolymerized holothurian glycosaminoglycan (DHG), unfractionated heparin (UFH), and low-molecular-weight heparin (LMWH) by protamine sulfate (PS) or platelet factor 4 (PF4) was studied. In in vitro studies, the prolongation of thrombin clotting time (TCT) by these glycos-aminoglycans was completely neutralized by PS, whereas activated partial thromboplastin time (APTT) was relatively resistant to neutralization. In rats, prolongation of bleeding time by DHG was neutralized by PS with concomitant normalization of TCT ex vivo. Heparin-cofactor-II-dependent antithrombin activity of DHG or UFH was neutralized by PF4 at a high concentration to the same extent; however, prolongation of the APTT by DHG was more resistant to neutralization by PF4 at a physiological plasma level than that by UFH. In conclusion, since the prolongation of bleeding time by DHG was neutralized by PS with concomitant normalization of TCT, and since PF4 neutralized the antithrombin activity of DHG, these proteins may be useful as antidotes for DHG to prevent bleeding in case of an overdose.
Effect of Race on the Clinical Outcomes in the Bypass Angioplasty Revascularization Investigation Trial
Authors: Melsop Kathryn , Brooks Maria M. , Boothroyd Derek B. , Hlatky Mark A.
Published: April 2009

Background—

In observational studies, clinical outcomes for black patients with coronary disease have been worse than for white patients. There are few data from randomized trials comparing the outcomes of coronary revascularization between black patients and white patients.

Methods and Results—

We analyzed data from the Bypass Angioplasty Revascularization Investigation randomized trial. At study entry, the 113 black patients had significantly higher rates of diabetes, hypertension, smoking, heart failure, and abnormal left ventricular function than the 1653 white patients. Black patients had significantly higher mortality than white patients (hazard ratio, 2.16;
P
<0.001), which remained significant after statistical adjustment for differences in baseline clinical characteristics (hazard ratio, 1.59;
P
=0.003). In a substudy of economic and quality of life outcomes, the 67 black patients had similar frequency of physician visits and use of evidence-based cardiac medications but significantly worse physical function scores than the 885 white patients. The effect of random assignment to either surgery or angioplasty on clinical outcomes was not significantly modified by race (interaction probability values ≥0.18).

Conclusions—

Clinical outcomes of black patients after coronary revascularization were worse than those of white patients in a clinical trial setting with similar treatment and access to care. The differences in outcome between black and white patients were not completely attributable to the greater levels of comorbidity among black patients at study entry.
Use of Guidelines-Recommended Management and Outcomes Among Women and Men With Low-Level Troponin Elevation
Authors: Halim Sharif A. , Mulgund Jyotsna , Chen Anita Y. , Roe Matthew T. , Peterson Eric D. , Gibler W. Brian , Ohman E. Magnus , Newby L. Kristin
Published: April 2009

Background—

Troponin elevation above the upper limit of normal (ULN) is diagnostic of myocardial infarction, but interpretation of “gray-zone” troponin elevations (1 to 1.5� ULN) remains uncertain. Using the CRUSADE database, we explored relationships between sex and treatment and outcomes among patients with troponin 1 to 1.5� ULN.

Methods and Results—

We compared treatment and outcomes among women and men using logistic generalized estimating equation method. Overall, 5049 of 85 671 (5.9%) non–ST-segment elevation acute coronary syndromes patients (2156 women, 2893 men) had troponin 1 to 1.5� ULN within 24 hours of presentation. Compared with troponin >1.5� ULN, “gray-zone” patients less often received all guidelines-indicated acute (mean composite score, 63% versus 72%) and discharge therapies (mean composite score, 73% versus 78%), but received them more frequently than patients with troponin <1� ULN (mean composite scores, 58% acute and 67% discharge). Among “gray-zone” patients, acute and discharge therapy use was similar between women and men, except acute aspirin (adjusted odds ratio, 0.80 [95% CI, 0.65 to 0.98]) and discharge angiotensin-converting enzyme inhibitors (adjusted odds ratio, 0.77 [95% CI, 0.67 to 0.88]). “Gray-zone” patients had lower mortality (2.3%) than the >1.5� ULN (4.5%) group but higher than the <1� ULN group (1.1%). Outcomes were similar among “gray-zone” women and men (adjusted odds ratios: death, 0.88 [95% CI, 0.58 to 1.35]; death/myocardial infarction, 0.77 [95% CI, 0.55 to 1.06]; transfusion, 1.04 [95% CI, 0.85 to 1.27]).

Conclusions—

Patients with non–ST-segment elevation acute coronary syndromes and low-level troponin elevations had lower overall risk and received less aggressive guidelines-based treatment than those with greater troponin elevations, but treatment patterns were largely similar by sex across troponin elevation groups.
Changes in Adherence to Evidence-Based Medications in the First Year After Initial Hospitalization for Heart Failure
Authors: Lamb Darcy A. , Eurich Dean T. , McAlister Finlay A. , Tsuyuki Ross T. , Semchuk William M. , Wilson Thomas W. , Blackburn David F.
Published: April 2009

Background—

The use of evidence-based medications in patients with heart failure has increased over the past 10 years. We aimed to determine whether adherence to these medications has also increased during this time.

Methods and Results—

A retrospective cohort was created using administrative databases from the province of Saskatchewan, Canada. Subjects discharged alive from their first hospitalization for heart failure between 1994 and 2003 were eligible. Those filling a prescription for a β-blocker (BB), angiotensin-converting enzyme inhibitor (ACEI), or angiotensin receptor blocker (ARB) within 6 months of discharge were followed for 1 year after the initial prescription. Of 8805 eligible patients, 67% of BB users (941/1414) and 74% of ACEI/ARB users (4441/5991) exhibited optimal adherence at 1 year (defined as ≥80% adherence calculated from pharmacy refill records). When grouped by year of initial heart failure hospitalization, the proportion of optimally adherent patients improved from 54% to 75% with BB and from 67% to 80% with ACEI/ARBs between 1994/1995 and 2002/2003 (
P
for trend <0.001 for both). Mean 1-year adherence improved from 71% to 83% for BB and 80% to 88% for ACEI/ARBs. After adjustment using multivariable logistic regression, subjects discharged in 2003 were significantly more likely to exhibit optimal adherence to a BB (odds ratio, 2.04; 95% CI, 1.21 to 3.44) or an ACEI/ARB (odds ratio, 1.65; 95% CI, 1.30 to 2.08) than those prescribed therapy in 1994/1995.

Conclusions—

One-year adherence to BB and ACEI/ARB is improving over time in patients discharged after first heart failure hospitalization. Patients taking multiple cardiac medications were not any less likely to exhibit optimal adherence than patients taking only 1 medication.
Understanding Why Patients Delay Seeking Care for Acute Coronary Syndromes
Authors: Sullivan Mark D. , Ciechanowski Paul S. , Russo Joan E. , Soine Laurie A. , Jordan-Keith Kier , Ting Henry H. , Caldwell James H.
Published: April 2009

Background—

Better insight into the psychosocial factors associated with prehospital delays in seeking care for acute coronary syndromes is needed to inform the design of future interventions. Delay in presenting for care after the onset of symptoms is common, limits the potential benefit of acute reperfusion, and has not been reduced by interventions tested thus far.

Methods and Results—

Seven hundred ninety-six patients with suspected ischemic heart disease scheduled for clinically indicated imaging stress tests completed questionnaires concerning psychological distress and attachment styles (worthiness to receive care, trustworthiness of others to provide care). The primary dependent variable for this study was response to a question from the rapid early action for coronary treatment trial concerning intention to “wait until very sure” before seeking care for a possible “heart attack.” Responses to this question were strongly associated with actual emergency department-reported and self-reported care delay in the rapid early action for coronary treatment trial. In multivariable ordinal regression models, a more negative view of the trustworthiness of others, greater physical limitations from angina, and no previous revascularization were independently associated with increased intention to wait to seek care for a myocardial infarction. Intention to wait was not associated with inducible ischemia or self-perceived risk of myocardial infarction.

Conclusions—

Intention to delay seeking care for acute coronary syndromes is associated with a patient’s view of the trustworthiness of others, previous experience with revascularization, and functional limitations, even after adjustment for objective and perceived acute coronary syndromes risk. These findings provide insight into novel factors contributing to longer delay times and may inform future interventions to reduce delay time.
Psychiatric Comorbidity and Mortality After Acute Myocardial Infarction
Authors: Abrams Thad E. , Vaughan-Sarrazin Mary , Rosenthal Gary E.
Published: April 2009

Background—

Prior studies of the impact of psychiatric comorbidity on outcomes after acute myocardial infarction (AMI) have frequently relied on inpatient secondary diagnosis codes. This study compared associations between psychiatric comorbidity and AMI outcomes that were derived using secondary diagnosis codes and codes captured from prior outpatient encounters.

Methods and Results—

Retrospective cohort study analyzing 21 745 patients admitted in 2004 to 2006 to Veterans Health Administration hospitals with AMI using administrative data. Psychiatric comorbidity was identified using (1) secondary inpatient diagnosis codes from the index hospitalization and (2) diagnoses from prior outpatient encounters. Outcomes included 30- and 365-day mortality and the receipt of coronary revascularization within 30 days of admission. Generalized estimating equations and Cox proportional hazards were used to adjust mortality and receipt of revascularization for demographic and clinical variables. Psychiatric disorders were identified in 2285 (10%) patients from inpatient secondary diagnosis codes and 5225 (24%) patients from prior outpatient codes. Patients with psychiatric comorbidity had higher adjusted 30- and 365-day mortality, based on outpatient codes (odds ratios, 1.19 [95% CI, 1.09 to 1.30] and 1.12 [95% CI, 1.03 to 1.22], respectively), but similar mortality based on inpatient codes (odds ratios, 0.89 [95% CI, 0.69 to 1.01] and 0.93 [95% CI, 0.82 to 1.06], respectively). In contrast, patients with psychiatric comorbidity had lower receipt of coronary revascularization based on outpatient codes (hazard ratio, 0.92; [95% CI, 0.85 to 0.99], but similar receipt based on inpatient codes (hazard ratio, 1.00 [95% CI, 0.91 to 1.10]).

Conclusions—

Inpatient secondary diagnosis codes identified fewer patients with psychiatric comorbidity than prior outpatient codes. Moreover, associations with AMI outcomes differed for the 2 approaches. These findings raise potential concerns about the validity and reliability of psychiatric inpatient secondary diagnosis in estimating the impact of psychiatric comorbidities on AMI outcomes and in developing risk-adjustment models.
Arctic Mixed-Phase Stratiform Cloud Properties from Multiple Years of Surface-Based Measurements at Two High-Latitude Locations
Authors: de Boer Gijs , Eloranta Edwin W. , Shupe Matthew D.
Published: April 2009

Macro- and microphysical properties of single-layer stratiform mixed-phase clouds are derived from multiple years of lidar, radar, and radiosonde observations. Measurements were made as part of the Mixed-Phase Arctic Clouds Experiment (MPACE) and the Study of Environmental Arctic Change (SEARCH) in Barrow, Alaska, and Eureka, Nunavut, Canada, respectively. Single-layer mixed-phase clouds occurred between 4% and 26% of the total time observed, varying with season and location. They had mean cloud-base heights between ∼700 and 2100 m and thicknesses between ∼200 and 700 m. Seasonal mean cloud optical depths ranged from 2.2 up. The clouds existed at temperatures of ∼242–271 K and occurred under different wind conditions, depending on season. Utilizing retrievals from a combination of lidar, radar, and microwave radiometer, mean cloud microphysical properties were derived, with mean liquid effective diameters estimated from 16 to 49 μm, mean liquid number densities on the order of 104–105 L−1, and mean water contents estimated between 0.07 and 0.28 g m−3. Ice precipitation was shown to have mean ice effective diameters of 50–125 μm, mean ice number densities on the order of 10 L−1, and mean water contents estimated between 0.012 and 0.031 g m−3. Mean cloud liquid water paths ranged from 25 to 100 g m−2. All results are compared to previous studies, and potential retrieval errors are discussed. Additionally, seasonal variation in macro- and microphysical properties was highlighted. Finally, fraction of liquid water to ice mass was shown to decrease with decreasing temperature.
The Basic Ingredients of the North Atlantic Storm Track. Part I: Land–Sea Contrast and Orography
Authors: Brayshaw David James , Hoskins Brian , Blackburn Michael
Published: April 2009

Understanding and predicting changes in storm tracks over longer time scales is a challenging problem, particularly in the North Atlantic. This is due in part to the complex range of forcings (land–sea contrast, orography, sea surface temperatures, etc.) that combine to produce the structure of the storm track. The impact of land–sea contrast and midlatitude orography on the North Atlantic storm track is investigated through a hierarchy of GCM simulations using idealized and “semirealistic” boundary conditions in a high-resolution version of the Hadley Centre atmosphere model (HadAM3). This framework captures the large-scale essence of features such as the North and South American continents, Eurasia, and the Rocky Mountains, enabling the results to be applied more directly to realistic modeling situations than was possible with previous idealized studies. The physical processes by which the forcing mechanisms impact the large-scale flow and the midlatitude storm tracks are discussed. The characteristics of the North American continent are found to be very important in generating the structure of the North Atlantic storm track. In particular, the southwest–northeast tilt in the upper tropospheric jet produced by southward deflection of the westerly flow incident on the Rocky Mountains leads to enhanced storm development along an axis close to that of the continent’s eastern coastline. The approximately triangular shape of North America also enables a cold pool of air to develop in the northeast, intensifying the surface temperature contrast across the eastern coastline, consistent with further enhancements of baroclinicity and storm growth along the same axis.
Temporal–Spatial Distribution of Thin Moist Layers in the Midtroposphere over the Tropical Eastern Pacific
Authors: Otsuka Shigenori , Yoden Shigeo
Published: April 2009

The temporal–spatial distribution of thin moist layers in the midtroposphere over the tropical eastern Pacific is studied by data analyses of radiosonde soundings and downscaling numerical experiments with a regional model. Radiosonde soundings at San Cristóbal, Galápagos, show frequent existence of thin moist layers between 2 and 10 km in altitude, with a local minimum at 7–8 km. The downscaling experiments with global objective analyses are completed for 2005–06, September and December of 1999–2004, and March of 2000–04. The vertical distribution of thin moist layers has three local maxima at 5, 10, and 16 km, where bimodality of the frequency distribution of water vapor is evident. Between 4 and 7 km, an annual variation is dominant in the occurrence ratio of thin moist layers, which tend to appear in nonconvective regions. In boreal winter, the layers appear to the north of the intertropical convergence zone (ITCZ), whereas in boreal summer the layers appear in the equator-side of the ITCZ. Interannual variations of the appearance of thin moist layers are also studied in 1999–2006, based on the experiments for particular months (March, September, and December). The occurrence ratio is generally high in December and March and low in September. In La Niña years, the annual variation is smaller than that in El Niño years; the occurrence ratio is higher in boreal summer to the south of the ITCZ.
Predictions of Indian Ocean SST Indices with a Simple Statistical Model: A Null Hypothesis
Authors: Dommenget Dietmar , Jansen Malte
Published: April 2009

Several recent general circulation model studies discuss the predictability of the Indian Ocean dipole (IOD) mode, suggesting that it is predictable because of coupled ocean–atmosphere interactions in the Indian Ocean. However, it is not clear from these studies how much of the predictability is due to the response to El Niño. It is shown in this note that a simple statistical model that treats the Indian Ocean as a red noise process forced by tropical Pacific SST shows forecast skills comparable to those of recent general circulation model studies. The results also indicate that some of the eastern tropical Indian Ocean SST predictability in recent studies may indeed be beyond the skill of the simple model proposed in this note, indicating that dynamics in the Indian Ocean may have caused this improved predictability in this region. The model further indicates that the IOD index may be the least predictable index of Indian Ocean SST variability. The model is proposed as a null hypothesis for Indian Ocean SST predictions.
Comparison between the Large-Scale Environments of Moderate and Intense Precipitating Systems in the Mediterranean Region
Authors: Funatsu Beatriz M. , Claud Chantal , Chaboureau Jean-Pierre
Published: April 2009

A characterization of the large-scale environment associated with precipitating systems in the Mediterranean region, based mainly on NOAA-16 Advanced Microwave Sounding Unit (AMSU) observations from 2001 to 2007, is presented. Channels 5, 7, and 8 of AMSU-A are used to identify upper-level features, while a simple and tractable method, based on combinations of channels 3–5 of AMSU-B and insensitive to land–sea contrast, was used to identify precipitation. Rain occurrence is widespread over the Mediterranean in wintertime while reduced or short lived in the eastern part of the basin in summer. The location of convective precipitation shifts from mostly over land from April to August, to mostly over the sea from September to December. A composite analysis depicting large-scale conditions, for cases of either rain alone or extensive areas of deep convection, is performed for selected locations where the occurrence of intense rainfall was found to be important. In both cases, an upper-level trough is seen to the west of the target area, but for extreme rainfall the trough is narrower and has larger amplitude in all seasons. In general, these troughs are also deeper for extreme rainfall. Based on the European Centre for Medium-Range Weather Forecasts operational analyses, it was found that sea surface temperature anomalies composites for extreme rainfall are often about 1 K warmer, compared to nonconvective precipitation conditions, in the vicinity of the affected area, and the wind speed at 850 hPa is also stronger and usually coming from the sea.
Explaining Grammatical Variation and Change: A Case Study of Complementation in American English over Three Decades
Authors: Rudanko Juhani
Published: April 2009

This article examines sentential complements of the adjective accustomed involving subject control in the 1930s, 1940s, and 1950s on the basis of the TIME Magazine Corpus. Two specific principles are identified to explain the argument structure properties of accustomed. The first is the role of extractions, which is shown to have played a significant role in the 1930s in favor of to infinitives.The other principle is semantic: when the situation encoded by the lower clause predicate involves agentivity and choice on the part of the lower subject, the complement is likely to be of the to infinitive form in the 1930s, whereas a lower clause with a [—Choice] predicate is likely to be of the to -ing type. In the 1940s and 1950s, the to infinitive declines rapidly in frequency, with the to -ing pattern becoming entrenched even in contexts that had favored to infinitives earlier.
Did You See It Coming?
Authors: Palomares Nicholas A.
Published: April 2009

To test aspects of a theoretical framework on goal detection in social interaction, an experiment examined dyadic initial interactions wherein one participant pursued a goal unbeknownst to another participant. The level of specificity and efficiency at which a pursuer sought a goal interacted to affect the accuracy of the detector's inference as well as the time of onset for that inference. Consistent with hypotheses, efficiency was unrelated to accuracy and negatively correlated with onset latency when pursuers had an abstract information-seeking goal, whereas efficiency was positively correlated with accuracy and onset latency when detecting a concrete (i.e., specific) information-seeking goal. Unexpectedly, efficiency was unrelated to accuracy and onset latency for a midlevel information-seeking goal. Other results focused on the role of individual differences (i.e., perspective-taking and suspicion in others' motives) and perceived communication competence in the goal detection process. A more controlled, second experiment that employed confederates generally replicated results.