Effects of MitraClip on cognitive and psychological function in heart failure patients: the sicker the better

Purpose: Cognitive impairment and reduced quality of life is a common condition in patients with heart failure (HF). Percutaneous mitral valve repair using (PMVR) MitraClip (MC) has emerged as a promising interventional tool, reducing all-cause mortality and hospitalization as well as increasing cognitive functioning and quality of life. However, the benefit of HF patients with severely depressed cognitive functioning remains unknown. Methods: We assessed cognitive functioning (figural memory—FGT, executive function—TOL, TMT B), psychosocial functioning (depression—PHQ-9, quality of life—SF36), and clinical parameters (echocardiography, 6-min walk test distance, and cardiac biomarkers) 1 day before (t0) and 6 weeks after (t1) MC intervention in HF patients (n = 40). First, paired sample t tests were conducted to uncover improvements in cognitive functioning post-MC intervention. Second, the COGBAT Norm-sample, a representative age-matched healthy sample, was used to compare participants’ individual scores. Third, bivariate linear regressions were calculated for all key predictors of the detected improvements in cognitive functioning post-MC intervention (t1–t0). Results: Following the MC intervention, we found significant improvements in figural memory, executive functioning, and psychosocial functioning. Most of the patients with depressed executive functioning before the MC intervention showed post-intervention test scores within the normal range (> 50th percentile; t0 22.5% vs. t1 60%) as compared to the normative COGBAT sample. Regression analyses revealed that lower baseline scores in planning ability before the MC intervention (t0) were associated with greater planning ability (TOL; B = − 0.78, 95% CI − 1.04 to − 0.53), figural memory (FGT; B = − 0.26, 95% CI − 0.44 to − 0.07), and cognitive flexibility (TMT B; B = − 0.36, 95% CI − 0.50 to − 0.23) improvement post-MC intervention (t1–t0). Psychosocial functioning and age were not associated with these improvements. Conclusions: Patients with depressed executive functioning showed the greatest benefit from the MC intervention regarding cognitive functioning. Age and psychological functioning seem less important for cognitive performance improvements post-MC intervention. Hence, severely depressed cognitive functioning in patients is not a contraindication for PMVR using MitraClip

Prevention and treatment of experimental thrombosis in rabbits with rivaroxaban (BAY 597939) - an oral, direct factor Xa inhibitor

Current anticoagulant therapies for the prevention and treatment of thromboembolic disorders have many drawbacks: vitamin K antagonists interact with food and drugs and require frequent laboratory monitoring, and heparins require parenteral administration. Oral rivaroxaban (BAY 597939) is a new, highly selective and potent direct factor-Xa (FXa) inhibitor with a predictable pharmacodynamic and pharmacokinetic profile and could therefore be an attractive antithrombotic drug. It was the objective of this study to investigate the antithrombotic efficacy of oral rivaroxaban in two rabbit models of experimental venous thrombosis. In the venous stasis (prevention) model, animals were randomized to receive oral rivaroxaban 0.3, 1.0, 3.0 or 10.0 mg/kg or vehicle control. Thrombosis was induced by jugular vein stasis and injection of thromboplastin into the ear vein. In the venous thrombosis (treatment) model, intravenous (1.0 and 3.0 mg/kg) and oral (3.0 mg/kg) rivaroxaban was compared with intravenous nadroparin (40 U bolus and 20 U/h), fondaparinux (42 mu g/kg) and vehicle control. Thrombus growth was assessed by measuring the accretion of radiolabelled fibrinogen into preformed clots in the jugular veins. Bleeding was assessed using an ear bleeding model. In the prevention model, rivaroxaban reduced thrombus formation dose-dependently (calculated ED50 1.3 mg/kg). In the treatment model, oral rivaroxaban (3.0 mg/kg) reduced thrombus growth to a similar extent to intravenous rivaroxaban (1.0 mg/kg), nadroparin and fondaparinux. Oral rivaroxaban did not prolong bleeding time. In conclusion, the orally available selective, direct FXa inhibitor rivaroxaban is effective in the prevention and treatment of venous thrombosis in two well-established models of experimental thrombosi

Patient-controlled analgesia versus continuous infusion of morphine during vaso-occlusive crisis in sickle cell disease, a randomized controlled trial

Intravenous morphine is the treatment of choice for severe pain during vaso- occlusive crisis in sickle cell disease (SCD). However, side effects of morphine may hamper effective treatment, and high plasma levels of morphine are associated with severe complications such as acute chest syndrome. Furthermore, adequate dosing remains a problem since no objective measurement of pain severity exists and analgesia should be titrated upon the patient's reported pain. Patient-controlled analgesia (PCA) may therefore be an interesting alternative since patients can titrate the level of analgesia themselves. In this randomized controlled study, the efficacy of intravenous morphine administration with PCA was compared with continuous infusion (CI) of morphine in patients with SCD during vaso-occlusive crisis. Twenty five consecutive episodes of vaso-occlusive crisis in 19 patients with SCD were included in the study. Patients in the PCA-group had a markedly and significant lower mean and cumulative morphine consumption when compared with the patients in the CI-group (0.5 mg/hr versus 2.4 mg/hr (P < 0.001) and 33 mg versus 260 mg (P = 0.018, respectively). The mean daily pain scores were comparable (4.9 versus 5.3). The lower mean and cumulative morphine consumption in the PCA-group led to significant less nausea and constipation during treatment when compared with the CI-group (area under the curve, respectively, 11 versus 18 (P = 0.045) and 30 versus 45 (P = 0.021). Furthermore, a nonsignificant reduction in the duration of hospital admission of 3 days was observed in the PCA-group. PCA results in adequate pain relief at a much lower morphine consumption and should considered to be the first choice in morphine administration to sickle cell patients admitted with vaso-occlusive crisi

Activation of coagulation by administration of recombinant factor VIIa elicits interleukin 6 (IL-6) and IL-8 release in healthy human subjects

The activation of coagulation has been shown to contribute to proinflammatory responses in animal and in vitro experiments. Here we report that the activation of coagulation in healthy human subjects by the administration of recombinant factor VIIa also elicits a small but significant increase in the concentrations of interleukin 6 (IL-6) and IL-8 in plasma. This increase was absent when the subjects were pretreated with recombinant nematode anticoagulant protein c2, the inhibitor of tissue factor-factor VII

Effect of recombinant activated factor VII on perioperative blood loss in patients undergoing retropubic prostatectomy: a double-blind placebo-controlled randomised trial

BACKGROUND: Recombinant activated factor VII (factor VIIa) has prohaemostatic effects in bleeding patients with coagulation abnormalities. We aimed to test the hypothesis that recombinant factor VIIa could reduce perioperative blood loss in patients with normal coagulation systems. Therefore, we assessed safety and efficacy of this drug in patients undergoing retropubic prostatectomy, which is often associated with major blood loss and need for transfusion. METHODS: In a double-blind, randomised placebo-controlled trial, we recorded blood loss and transfusion requirements in 36 patients undergoing retropubic prostatectomy, who were randomised to receive an intravenous bolus of recombinant factor VIIa (20 microg/kg or 40 microg/kg) or placebo in the early operative phase. FINDINGS: Median perioperative blood loss was 1235 mL (IQR 1025-1407) and 1089 mL (928-1320) in groups given recombinant factor VIIa 20 microg/kg and 40 microg/kg, respectively, compared with 2688 mL (1707-3565) in the placebo group (p=0.001). Seven of twelve placebo-treated patients were transfused, whereas no patients who received 40 microg/kg recombinant factor VIIa needed transfusion. The odds ratio for receiving any blood product in patients treated with recombinant factor VIIa compared with control patients was 0 (95% CI 0.00-0.33) No adverse events arose. INTERPRETATION: An injection of recombinant factor VIIa can reduce perioperative blood loss and eliminate the need for transfusion in patients undergoing major surger

Rapid Publication Enhancement of Rabbit Jugular Vein Thrombolysis by Neutralization of Factor XI In Vivo Evidence for a Role of Factor XI as an Anti-fibrinolytic Factor

Recent in vitro studies have shown that fibrinolytic activity may be attenuated by a thrombin-activatable fibrinolysis inhibitor (TAFI), which is activated by thrombin, generated via the intrinsic pathway of coagulation in a factor XI–dependent way. Thus factor XI may play a role in the regulation of endogenous fibrinolysis. The aim of this study was to investigate the effect of in vivo inhibition of factor XI and TAFI in an experimental thrombosis model in rabbits. Incorporation of anti–factor XI antibodies in jugular vein thrombi resulted in an almost twofold increase in endogenous thrombolysis compared with a control antibody. A similar effect was observed when the anti–factor XI antibody was administered systemically. Inhibition of TAFI activity also resulted in a twofold increase in clot lysis whereas inhibition of both factor XI and TAFI activity had no additional effect. Thus, we provide the first in vivo evidence for enhanced thrombolysis through inhibition of clotting factor XI, demonstrating a novel role for the intrinsic pathway of coagulation. Furthermore we demonstrate that inhibition of TAFI had a similar effect on thrombolysis. We postulate that inhibition of factor XI activity enhances thrombolysis because of diminished indirect activation of TAFI. (J. Clin. Invest

REtrieval And cure of Chronic Hepatitis C (REACH) : Results of micro-elimination in the Utrecht province

Background: The Netherlands is one of the six European countries considered on track to eliminate hepatitis C virus by 2030. To achieve this goal, continuous efforts have to be put into designing efficient case-finding strategies, including the retrieval of previously diagnosed hepatitis C virus-infected who are lost to follow-up. Aims: To trace and treat all lost to follow-up hepatitis C virus patients in the Utrecht region and create an efficient retrieval strategy that can be used in future (national) retrieval initiatives. Methods: Positive hepatitis C virus diagnostic tests (anti-hepatitis C virus IgG or hepatitis C virus-RNA) from the laboratory of all four hospitals and one central laboratory for primary care diagnostics in the province of Utrecht from 2001 to 2015 were linked to clinical records. Untreated patients with available contact information were deemed eligible for retrieval and invited for reevaluation with (virology) blood tests, fibroscan measurement and possible direct-acting antiviral therapy. Main results: After screening all hepatitis C virus diagnostics, 1913 chronic hepatitis C virus-infected were identified of which 14.1% (n = 269) were invited back into care. Overall, 17.4% was traced with the highest yield (28.3%) in those who lived in the Utrecht province. Through renewed patient assessments, 42 chronic hepatitis C virus infections were re-identified (76% with a history of intravenous drug use, 24% with Metavir F3-F4). Until now, 59% has either scheduled or initiated direct-acting antiviral therapy. Conclusion: The retrieval of previously diagnosed hepatitis C virus patients through screening of laboratory diagnostics from the past is feasible and should be pursued for further control and reduction of hepatitis C virus infection. Retrieval is most successful when performed regionally. Lay summary: To completely eliminate chronic hepatitis C virus (HCV) infection and prevent complications, undiagnosed and also previously diagnosed but lost to follow-up (LFU) HCV patients have to be brought (back) into care for therapy. Retrieval of LFU HCV patients through screening of laboratory diagnostics from the past is feasible and most successful when performed regionally