scholarly journals P1371HEART FAILURE HOSPITALISATIONS IN THE PIVOTAL TRIAL OF IV IRON IN HAEMODIALYSIS PATIENTS: A PRE-SPECIFIED SECONDARY ANALYSIS

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Pardeep Jhund ◽  
Mark Petrie ◽  
Michele Robertson ◽  
Patrick Mark ◽  
Michael Macdonald ◽  
...  
Keyword(s):  
Heart Failure ◽  
Low Dose ◽  
Randomised Trial ◽  
Recurrent Event ◽  
High Dose ◽  
Iron Group ◽  
Dose Strategy ◽  
Iv Iron ◽  
Cardiovascular Endpoint ◽  
The Impact

Abstract Background and Aims Heart failure (HF) is a common and potentially deadly complication in patients receiving haemodialysis which is difficult to diagnose and treat. The impact of a proactive high-dose strategy compared to a reactive low-dose strategy of IV iron administration was investigated in the PIVOTAL randomised trial in incident haemodialysis patients, with fatal HF and HF hospitalisation being components of the composite primary cardiovascular endpoint as well as a pre-specified key secondary event. The aim of this analysis was to examine the effect of a proactive high-dose strategy compared to a reactive lower dose strategy on HF events in patients recruited to PIVOTAL. Method As with the primary composite cardiovascular endpoint, HF hospitalisations in PIVOTAL were recorded prospectively via an electronic database, and events were then adjudicated by a blinded Endpoint Adjudication Committee. The time-to-event analyses of the primary, secondary and post hoc outcomes were performed in the intention-to-treat population using Cox proportional hazards regression, with treatment group as the only explanatory variable. The Kaplan–Meier method was used to estimate event rates. Both fatal and non-fatal HF events were analysed as time to first event, and a recurrent event analysis was also performed for non-fatal events. Results Overall, 2141 participants were followed for a median of 2.1 years. A first fatal or non-fatal HF event occurred in 51 of 1093 patients (4.7%) in the high-dose iron group and in 70 of 1048 patients (6.7%) in the low-dose iron group (hazard ratio 0.66, 95% confidence interval 0.46 to 0.94; P<0.001) (Figure). There was a total of 63 HF events (including first and recurrent events) in the high-dose iron group and 98 in the low-dose iron group, giving a rate ratio of 0.59 (0.40-0.87); p=0.0084. A history of HF and diabetes were independent predictors of a heart failure event. Conclusion Compared with a low-dose regimen, high-dose intravenous iron decreased the occurrence of first and recurrent heart failure events in incident patients undergoing haemodialysis, with large relative and absolute risk reductions.

Abstract 11983: Auraptene, a Coumaric Compounds Analogous, Improved the Worsening of Systolic Function by Activating Mitochondrial Function After Myocardial Infarction in Rats

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Yoichi Sunagawa ◽  
Miho Suzuki ◽  
Masafumi Funamoto ◽  
Yasufumi Katanasaka ◽  
Hidetoshi Suzuki ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Lipid Metabolism ◽  
Mitochondrial Function ◽  
Low Dose ◽  
Systolic Function ◽  
Pharmacological Therapy ◽  
Vehicle Group ◽  
High Dose ◽  
Related Gene

Introduction: Heart failure is associated with pathological growth and mitochondrial dysfunction of constituent cardiomyocytes. To achieve effective oral pharmacological therapy for heart failure, we screened compounds isolated from natural products and found that auraptene derived from the peel of Citrus Hassaku may be applicable to pharmacological therapy for heart failure. Hypothesis: We assessed the hypothesis that auraptene could improve the deterioration of mitochondrial function and the development of heart failure in rats with myocardial infarction (MI). Methods and Results: In cultured cardiomyocytes, auraptene (2.5-10 μM) dose-dependently repressed phenylephrine-induced hypertrophic responses such as increase in cell size and ANF and ET-1 promoter activations. Auraptene also activated mitochondrial- and lipid metabolism-related gene transcriptions, such as PGC1α, PPARα/γ, mCPT1, UCP3, and PDK4. One week after operation, 22 rats with a moderate size of MI (Fractional shortening (FS) < 40%) were then randomly assigned to vehicle (n=8), auraptene low-dose (5 mg/kg/day, n=7), or high-dose (50 mg/kg/day, n=7). Oral daily treatments with these agents were continued for 6 weeks. There were no differences in left ventricle (LV) geometric and functional data among the 3 MI groups before treatment. After treatment, LVFS was significantly higher in the auraptene low-dose (21%, p < 0.0001) and high-dose (26%, p < 0.0001) groups than the vehicle group (16%). LV wall thickness in the remote non-infarct area was significantly thinner in the auraptene low-dose (1.4 mm, p < 0.01) and high-dose (1.2 mm, p < 0.0001) groups than the vehicle group (2.5 mm). Histological analysis demonstrated that auraptene treatment significantly suppressed MI-induced increases in myocardial cell diameter and perivascular fibrosis compared with vehicle treatment. Moreover, auraptene also prevented the activations of ANF and MCP-1 mRNA levels and up-regulated mitochondrial- and lipid metabolism-related gene transcriptions in LV. Conclusions: Auraptene treatment prevents the worsening of LV systolic function and represses hypertrophy after MI in adult rats. A natural compound, auraptene is expected as a novel useful agent for heart failure therapy in humans.

The impact of low-dose versus high-dose antibiotic prophylaxis regimens on surgical site infection rates after cesarean delivery

2019 ◽  
Vol 301 (1) ◽  
pp. 69-73 ◽  
Author(s):  
Mauricio La Rosa ◽  
Chasey Omere ◽  
Tiffany Redfern ◽  
Mahmoud Abdelwahab ◽  
Nicholas Spencer ◽  
...  
Keyword(s):  
Surgical Site Infection ◽  
Antibiotic Prophylaxis ◽  
Cesarean Delivery ◽  
Low Dose ◽  
High Dose ◽  
Site Infection ◽  
Infection Rates ◽  
The Impact

Prevention Of Deep Vein Thrombosis In Medical Patients By Low Dose Subcutaneous Heparin

1981 ◽  
Author(s):  
J J F Belch ◽  
G D O Lowe ◽  
A G Ward ◽  
C D Forbes ◽  
C R M Prentice
Keyword(s):  
Heart Failure ◽  
Deep Vein Thrombosis ◽  
Low Dose ◽  
Randomised Trial ◽  
Medical Patients ◽  
Chest Infection ◽  
Vein Thrombosis ◽  
Subcutaneous Heparin ◽  
Patients With Heart Failure ◽  
Deep Vein

In recent years it has been repeatedly shown that low-dose subcutaneous heparin reduces the incidence of deep vein thrombosis (D.V.T.) after major general surgery. By comparison, the prevention of thrombosis in medical patients has been little studied. A randomised trial was undertaken in one hundred patients with heart failure and/or chest infection to determine whether low-dose subcutaneous heparin reduced the frequency of D.V.T. in the legs. Heparin (5000 units 8 hourly), started within 12 hours of admission to hospital and continued until the patient was fully mobile, significantly reduced the frequency of D.V.T. diagnosed by the 125I- fibrinogen scan technique, from 26% to 4% (p<0.01). Heparin did not cause bleeding problems except for a 20% incidence of injection site bruising. We therefore recommend prophylaxis with low dose subcutaneous heparin in patients with heart failure or chest infection who require more than 3 days’ bed rest.

scholarly journals CD8+-T-Cell Response to Secreted and Nonsecreted Antigens Delivered by Recombinant Listeria monocytogenes during Secondary Infection

2002 ◽  
Vol 70 (1) ◽  
pp. 153-162 ◽  
Author(s):  
Amy R. Tvinnereim ◽  
Sara E. Hamilton ◽  
John T. Harty
Keyword(s):  
T Cells ◽  
Listeria Monocytogenes ◽  
T Cell ◽  
Cell Response ◽  
Low Dose ◽  
Recombinant Antigen ◽  
T Cell Response ◽  
Vector System ◽  
High Dose ◽  
The Impact

ABSTRACT Understanding how existing antivector immunity impacts live vaccine delivery systems is critical when the same vector system may be used to deliver different antigens. We addressed the impact of antivector immunity, elicited by immunization with attenuated actA-deficient Listeria monocytogenes, on the CD8+-T-cell response to a well-characterized lymphocytic choriomeningitis virus epitope, NP118-126, delivered by infection with recombinant L. monocytogenes. Challenges of immune mice with actA-deficient and with wild-type recombinant L. monocytogenes generated similar numbers of CD8+ T cells specific for the NP118-126 epitope. High-dose immunization with actA-deficient L. monocytogenes resulted in substantial numbers of CD8+ T cells specific for the L. monocytogenes LLO91-99 epitope in the effector and memory stages of the T-cell response. Challenge of these immune mice with recombinant L. monocytogenes resulted in rapid control of the infection and decreased CD8+-T-cell responses against both the secreted and nonsecreted form of the recombinant antigen compared to the response of naïve mice. In contrast, mice immunized with a low dose of actA-deficient L. monocytogenes had ∼10-fold fewer effector and memory T cells specific for LLO91-99 and a substantially higher CD8+-T-cell response against the recombinant antigen after challenge with recombinant L. monocytogenes. Although mice immunized with low-dose actA-deficient L. monocytogenes had a substantial recall response to LLO91-99, which reached the same levels by 5 to 7 days postchallenge as that in high-dose-immunized mice, they exhibited decreased ability to control L. monocytogenes replication. Thus, the level of antivector immunity impacts the control of infection and efficiency of priming responses against new antigens introduced with the same vector.

Do adjuvants add to the efficacy and tolerance of bowel preparations? A meta-analysis of randomized trials

Endoscopy ◽  
2017 ◽  
Vol 50 (02) ◽  
pp. 159-176 ◽  
Author(s):  
Sophie Restellini ◽  
Omar Kherad ◽  
Charles Menard ◽  
Myriam Martel ◽  
Alan Barkun
Keyword(s):  
Randomized Trials ◽  
Low Dose ◽  
Meta Analysis ◽  
High Dose ◽  
Detection Rates ◽  
Adenoma Detection ◽  
Adenoma Detection Rates ◽  
Split Dosing ◽  
Bowel Preparations ◽  
The Impact

Abstract Background and study aims Recommendations on adjuvant use with bowel preparations remain disparate. We performed a meta-analysis determining the clinical impact of adding an adjuvant to polyethylene glycol (PEG), sodium phosphate, picosulfate (PICO), or oral sulfate solutions (OSS)-based regimens. Methods Systematic searches were made of MEDLINE, EMBASE, Scopus, CENTRAL and ISI Web of knowledge for randomized trials from January 1980 to April 2016 that assessed preparations with or without adjuvants, given in split and non-split dosing, and PEG high- (> 3 L) or low-dose (≤ 2 L) regimens. Bowel cleansing efficacy was the primary outcome. Secondary outcomes included patient willingness to repeat the procedure, and polyp and adenoma detection rates. Results Of 3093 citations, 77 trials fulfilled the inclusion criteria. Overall, addition of an adjuvant compared with no adjuvant, irrespective of the type of preparation and mode of administration, yielded improvements in bowel cleanliness (odds ratio [OR] 1.23 [1.01 – 1.51]) without greater willingness to repeat (OR 1.40 [0.91 – 2.15]). Adjuvants combined with high-dose PEG significantly improved colon cleansing (OR 1.96 [1.32 – 2.94]). The odds for achieving adequate preparation with low-dose PEG with an adjuvant were not different to high-dose PEG alone (OR 0.95 [0.73 – 1.22]), but yielded improved tolerance (OR 3.22 [1.85 – 5.55]). However, split high-dose PEG yielded superior cleanliness to low-dose PEG with adjuvants (OR 2.53 [1.25 – 5.13]). No differences were noted for OSS and PICO comparisons, or for any products regarding polyp or adenoma detection rates. Conclusions Critical heterogeneity precludes firm conclusion on the impact of adjuvants with existing bowel preparations. Additional research is required to better characterize the methods of administration and resulting roles of adjuvants in an era of split-dosing.

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