5366 research outputs found
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Effects of Rivaroxaban on Biomarkers of Coagulation and Inflammation: A Post Hoc Analysis of the X-VeRT Trial.
No full textThis X-VeRT (eXplore the efficacy and safety of once-daily oral riVaroxaban for the prevention of caRdiovascular events in patients with nonvalvular aTrial fibrillation scheduled for cardioversion) substudy evaluated the effects of treatment with rivaroxaban or a vitamin-K antagonist (VKA) on levels of biomarkers of coagulation (D-dimer, thrombin-antithrombin III complex [TAT] and prothrombin fragment [F1.2]) and inflammation (high sensitivity C-reactive protein [hs-CRP] and high-sensitivity interleukin-6 [hs-IL-6]) in patients with atrial fibrillation (AF) who were scheduled for cardioversion and had not received adequate anticoagulation at baseline (defined as, in the 21 days before randomization: no oral anticoagulant; international normalized ratio <2.0 with VKA treatment; or <80% compliance with non-VKA oral anticoagulant treatment). Samples for biomarker analysis were taken at baseline ( = 958) and treatment completion (42 days after cardioversion; = 918). The influence of clinical characteristics on baseline biomarker levels and the effect of treatment on changes in biomarker levels were evaluated using linear and logistic models. Baseline levels of some biomarkers were significantly associated with type of AF (D-dimer and hs-IL-6) and with history of congestive heart failure (hs-CRP, D-dimer, and hs-IL-6). Rivaroxaban and VKA treatments were associated with reductions from baseline in levels of D-dimer (-32.3 and -37.6%, respectively), TAT (-28.0 and -23.1%, respectively), hs-CRP (-12.5 and -17.9%, respectively), and hs-IL-6 (-9.2 and -9.8%, respectively). F1.2 levels were reduced from baseline in patients receiving a VKA (-53.0%) but not in those receiving rivaroxaban (2.7%). Anticoagulation with rivaroxaban reduced levels of key inflammation and coagulation biomarkers to a similar extent as VKAs, with the exception of F1.2. Further investigation to confirm the value of these biomarkers in patients with AF is merited
A novel behavioural INTErvention to REduce Sitting Time in older adults undergoing orthopaedic surgery (INTEREST): results of a randomised-controlled feasibility study.
No full textBACKGROUND
Osteoarthritis is a prevalent condition in older adults that causes many patients to require a hip or knee replacement. Reducing patients' sedentariness prior to surgery may improve physical function and post-operative outcomes.
METHODS
We conducted a pragmatic randomised-controlled feasibility study with 2:1 allocation into intervention or usual care groups. The intervention, based on Self-Determination Theory, involved techniques to reduce sedentary behaviour, including motivational interviewing, setting of behavioural goals, and more. The primary outcome was feasibility, assessed using mixed methods. We included exploratory measures to inform a future definitive trial, such as ActivPal3 accelerometry to measure movement, the Short Physical Performance Battery (SPPB), Basic Psychological Needs, and cardiometabolic biomarkers. Assessments were at baseline, 1-week pre-surgery, and 6-week post-surgery.
RESULTS
We recruited 35 participants aged ≥ 60 years approximately 8 weeks before hip or knee arthroplasty. Participant uptake rate was 14.2%, and retention rate 85.7%. Participants were very satisfied with the study which was found to be feasible with some modifications. Exploratory within-group comparisons found that the intervention has potential to improve SPPB by 0.71 points from baseline to pre-surgery, a clinically significant increase, and reduce sedentary time by up to 66 min d.
CONCLUSION
In this older surgical population, it is feasible to use behavioural techniques to displace sedentary time to activity and to conduct a trial spanning the period of surgical intervention. This may improve physical function and surgical outcomes. The INTEREST intervention is now ready for evaluation in a full-scale randomised-controlled trial.
REGISTRATION
This trial was registered on Clinicaltrials.gov on 13/11/2018. ID: NCT03740412
In vitro endothelial hyperpermeability occurs early following traumatic hemorrhagic shock.
No full textBACKGROUND
Endothelial hyperpermeability is suggested to play a role in the development of microcirculatory perfusion disturbances and organ failure following hemorrhagic shock, but evidence is limited.
OBJECTIVE
To study the effect of plasma from traumatic hemorrhagic shock patients on in vitro endothelial barrier function.
METHODS
Plasma from traumatic hemorrhagic shock patients was obtained at the emergency department (ED), the intensive care unit (ICU), 24 h after ICU admission and from controls (n = 8). Sublingual microcirculatory perfusion was measured using incident dark field videomicroscopy at matching time points. Using electric cell-substrate impedance sensing, the effects of plasma exposure on in vitro endothelial barrier function of human endothelial cells were assessed.
RESULTS
Plasma from traumatic hemorrhagic shock patients collected at ED admission induced a 19% loss of in vitro endothelial resistance compared to plasma from controls (p 0.99). Interestingly, in vitro endothelial resistance showed a positive association with in vivo microcirculatory perfusion (r = 0.56, p < 0.01).
CONCLUSIONS
Plasma from traumatic hemorrhagic shock patients obtained following ED admission, but not at later stages, induced in vitro endothelial hyperpermeability. This coincided with in vivo microcirculatory perfusion disturbances
British Society for Rheumatology guideline on diagnosis and treatment of giant cell arteritis
No full textRestrictive Transfusion Practice in Adults Receiving Venovenous Extracorporeal Membrane Oxygenation: A Single-Center Experience.
No full textObjectives
Restrictive transfusion policies have been adopted in critical care, although these have not included patients receiving extracorporeal membrane oxygenation. We aimed to assess survival outcomes, adverse events related to RBC transfusion, and cost implications following a change from a "liberal" to a "restrictive" RBC transfusion practice in patients receiving extracorporeal membrane oxygenation.
Design
Retrospective observational study.
Setting
Single high-volume tertiary critical care department at a university hospital.
Patients
Patients 16 years old or greater receiving venovenous extracorporeal membrane oxygenation between 2011 and 2017 for more than 24 hours.
Interventions
None.
Measurements and Main Results
Clinical diagnoses, complications, outcomes, median hemoglobin, and hematocrit levels were obtained from patients' electronic records. All laboratory results for hemoglobin and hematocrit were included. RBC transfusions were obtained from prescription charts. We included 402 patients: 99 during a "liberal" transfusion practice (2011-2014)-when the target hemoglobin level was greater than 100 g/L; and 303 treated during a "restrictive" transfusion practice (2014-2017) when the target hemoglobin level was greater than 80 g/L. We found that survival outcomes did not change following the implementation of a "restrictive" transfusion policy. There was also a decrease in the extracorporeal blood flow rates with restrictive transfusion of 0.5 L/min. Nonsurvivors of venovenous extracorporeal membrane oxygenation had higher usage of RBC units following a change in transfusion practice. The restrictive strategy allowed a cost saving of £454 per patient.
Conclusions
These results suggest that the adoption of a more restrictive approach to RBC transfusion during venovenous extracorporeal membrane oxygenation is more cost-effective and associated with similar survival outcomes, than when compared with a more liberal approach
Exploring The Current Management Idiopathic Intracranial Hypertension, And Understanding The Role Of Dural Venous Sinus Stenting.
No full textIdiopathic Intracranial Hypertension (IIH) is a debilitating disorder characterised by raised intracranial pressure (ICP), papilloedema with the potential risk of permanent visual loss, and headaches that are profoundly disabling and reduce the quality of life. The first consensus guidelines have been published on investigation and management of adult IIH and one key area of uncertainty is the utility of dural venous sinus stenting for the management of headache and visual loss. There are an increasing number of series published and to help understand the successes and complications. During a patient physician priority setting, the understanding of the best type of intervention to treat IIH was assigned to the top 10 of most desired research questions for the disease. Ultimately randomised clinical trials (RCTs) in neurovascular stenting for IIH would be instructive, as the literature to date may suffer from publication bias. Due to the increasing incidence of IIH, there is no better time to systematically investigate interventions that may reverse the disease process and achieve remission. In this review we discuss the pathophysiology of IIH in relation to venous sinus stenosis, the role of venous sinus stenting with a review of the relevant literature, the advantages and disadvantages of stenting compared with other surgical interventions, and the future of stenting in the treatment of IIH
Association Between Fibrosis Stage and Outcomes of Patients with Non-Alcoholic Fatty Liver Disease: a Systematic Review and Meta-Analysis.
No full textBACKGROUND & AIMS
Biopsy-confirmed liver fibrosis is a prognostic factor for patients with non-alcoholic fatty liver disease (NAFLD). We performed a systematic review to quantify the prognostic value of fibrosis stage in patients with NAFLD and the subgroup of patients with non-alcoholic steatohepatitis (NASH) and to assess the evidence that change in fibrosis stage is a surrogate endpoint.
METHODS
We searched the MEDLINE, EMBASE, Cochrane Library, and trial registry databases through August 2018 for prospective or retrospective cohort studies of liver-related clinical events and outcomes in adults with NAFLD or NASH. We collected data on mortality (all-cause and liver-related) and morbidity (cirrhosis, liver cancer, and all liver-related events) by stage of fibrosis, determined by biopsy, for patients with NAFLD or NASH. Using fibrosis stage 0 as a reference population, we calculated fibrosis stage-specific relative risk (RR) and 95% CI values for mortality and morbidities. We performed fixed-effect and random-effect model meta-analyses. Meta-regression was used to examine associations among study design (prospective vs retrospective cohort), overall risk of bias (medium or high), and mean duration of follow up (in years).
RESULTS
Our meta-analysis included 13 studies, comprising 4428 patients with NAFLD; 2875 of these were reported to have NASH. Compared to no fibrosis (stage 0), unadjusted risk increased with increasing stage of fibrosis (stage 0 vs 4): all-cause mortality RR, 3.42 (95% CI, 2.63-4.46); liver-related mortality RR, 11.13 (95% CI, 4.15-29.84); liver transplantation RR, 5.42 (95% CI, 1.05-27.89), and liver-related events RR, 12.78 (95% CI, 6.85-23.85). The magnitude of RR did not differ significantly following adjustment for confounders including age or sex in the subgroup of NAFLD patients with NASH. Three studies examined the effects of increasing fibrosis on quality of life had inconsistent findings.
CONCLUSIONS
In a systematic review and meta-analysis, we found biopsy-confirmed fibrosis to be associated with risk of mortality and liver-related morbidity in patients with NAFLD, with and without adjustment for confounding factors and in patients with reported NASH. Further studies are needed to assess the association between fibrosis stage and patient quality of life and establish that change in liver fibrosis stage is a valid endpoint for use in clinical trials
Corrigendum to "HEART UK consensus statement on Lipoprotein(a): A call to action" [Atherosclerosis 291 (2019) 62-70].
No full textTherapeutic senescence via GPCR activation in synovial fibroblasts facilitates resolution of arthritis.
No full textRheumatoid arthritis affects individuals commonly during the most productive years of adulthood. Poor response rates and high costs associated with treatment mandate the search for new therapies. Here we show that targeting a specific G-protein coupled receptor promotes senescence in synovial fibroblasts, enabling amelioration of joint inflammation. Following activation of the melanocortin type 1 receptor (MC), synovial fibroblasts acquire a senescence phenotype characterized by arrested proliferation, metabolic re-programming and marked gene alteration resembling the remodeling phase of wound healing, with increased matrix metalloproteinase expression and reduced collagen production. This biological response is attained by selective agonism of MC, not shared by non-selective ligands, and dependent on downstream ERK1/2 phosphorylation. In vivo, activation of MC leads to anti-arthritic effects associated with induction of senescence in the synovial tissue and cartilage protection. Altogether, selective activation of MC is a viable strategy to induce cellular senescence, affording a distinct way to control joint inflammation and arthritis
