Use of alternative methodologies for evaluation of composite end points in trials of therapies for critical limb ischemia.
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ABSTRACT:
SUBMITTER: Subherwal S
PROVIDER: S-EPMC3950277 | biostudies-literature | 2012 Sep
REPOSITORIES: biostudies-literature
Publications
Use of alternative methodologies for evaluation of composite end points in trials of therapies for critical limb ischemia.
Subherwal Sumeet S Anstrom Kevin J KJ Jones William S WS Felker Michael G MG Misra Sanjay S Conte Michael S MS Hiatt William R WR Patel Manesh R MR
American heart journal 20120901 3
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Project description: Not available
| S-EPMC554039 | biostudies-literature
Project description:Background and purposeConventional analysis of vascular prevention trials assigns equal weight to disparate vascular events in a composite end point at variance with the public's perception of their differential impact on health outcome. This study sought to apply the disability-adjusted life-year (DALY) metric to differential weighting individual vascular end points in trial analyses.MethodsDALY values for the most common major end points in vascular prevention trials (nonfatal myocardial infarction, nonfatal stroke, and vascular death), were derived by using World Health Organization Global Burden of Disease Project methodology. The standardized DALYs for each event were applied to recent major primary and secondary vascular prevention trials and to hypothetical model trials.ResultsStandardized DALYs lost were 7.63 for nonfatal stroke, 5.14 for nonfatal myocardial infarction, and 11.59 for vascular death. In the published trials analyses, the direction of treatment effects was consistent between DALY and standard event analysis, but the rank order of treatment effect changed for 10 of 18 trials. The DALY analysis also permitted derivation of number-needed-to-treat values to gain 1 DALY: 2.1 for anticoagulation in atrial fibrillation, 2.7 for carotid endarterectomy in symptomatic stenosis, and 4.7 for clopidogrel added to aspirin in acute coronary syndrome. Hypothetical trial analyses demonstrated that the DALY metric more finely discriminates treatment effects.ConclusionsCompared with a nonfatal myocardial infarction, a nonfatal stroke causes a 1.48-fold greater loss and vascular death a 2.25-fold greater loss of DALY. DALY analysis integrates these valuations in a summary metric reflecting the net impact of therapy on patient and societal health, complementing conventional end point analyses.
| S-EPMC3109505 | biostudies-literature
Project description:Peripheral artery disease, caused by chronic arterial occlusion of the lower extremities, affects over 200 million people worldwide. Peripheral artery disease can progress into critical limb ischemia (CLI), its more severe manifestation, which is associated with higher risk of limb amputation and cardiovascular death. Aiming to improve tissue perfusion, therapeutic angiogenesis held promise to improve ischemic limbs using delivery of growth factors but has not successfully translated into benefits for patients. Moreover, accumulating studies suggest that impaired downstream signaling of these growth factors (or angiogenic resistance) may significantly contribute to CLI, particularly under harsh environments, such as diabetes mellitus. Noncoding RNAs are essential regulators of gene expression that control a range of pathophysiologies relevant to CLI, including angiogenesis/arteriogenesis, hypoxia, inflammation, stem/progenitor cells, and diabetes mellitus. In this review, we summarize the role of noncoding RNAs, including microRNAs and long noncoding RNAs, as functional mediators or biomarkers in the pathophysiology of CLI. A better understanding of these ncRNAs in CLI may provide opportunities for new targets in the prevention, diagnosis, and therapeutic management of this disabling disease state.
| S-EPMC7047615 | biostudies-literature
Project description:Critical limb ischemia (CLI) is a severe form of peripheral artery disease associated with high morbidity and mortality. The primary therapeutic goals in treating CLI are to reduce the risk of adverse cardiovascular events, relieve ischemic pain, heal ulcers, prevent major amputation, and improve quality of life (QoL) and survival. These goals may be achieved by medical therapy, endovascular intervention, open surgery, or amputation and require a multidisciplinary approach including pain management, wound care, risk factors reduction, and treatment of comorbidities. No-option patients are potential candidates for the novel angiogenic therapies. The application of genetic, molecular, and cellular-based modalities, the so-called therapeutic angiogenesis, in the treatment of arterial obstructive diseases has not shown consistent efficacy. This article summarizes the current status related to the management of patients with CLI and discusses the current findings of the emerging modalities for therapeutic angiogenesis.
| S-EPMC3761355 | biostudies-literature
Project description:This is a TMT-labeled proteomics analysis of human skeletal muscle specimens obtained from the following groups: older adult controls, critical limb ischemia patients undergoing surgical intervention, and critical limb ischemia patients undergoing limb amputation.
2021-10-06 | PXD021849 | JPOST Repository
Project description:ObjectivesHeavy cannabis use has been associated with the development of acute myocardial infarction and stroke. The objective of this study was to determine if heavy, chronic cannabis use is associated with the development of acute limb ischemia (ALI) or critical limb ischemia (CLI).MethodsWe conducted a retrospective cohort study within the National Inpatient Sample (2006-2015). Patients without cannabis use disorder (CUD) were matched to patients with CUD in a 2:1 ratio using propensity scores. Our primary outcomes were incidence of ALI and CLI. Secondary outcomes included incidence of acute mesenteric ischemia (AMI), chronic mesenteric ischemia (CMI), frequency of open or endovascular interventions, length of stay, and total costs. Sensitivity analyses were performed with alternative models, including in the entire unmatched cohort with regression models utilizing survey weights to account for sampling methodology.ResultsWe identified a cohort of 46,297 857 unmatched patients. Patients with CUD in the unmatched cohort were younger, with less cardiovascular risk factors, but higher rates of smoking and substance abuse. The matched cohort included 824,856 patients with CUD and 1,610,497 controls. Those with CUD had a higher incidence of ALI (OR 1.20 95% CI: 1.04-1.38 P=.016). Following multiple sensitivity analyses, there was no robust association between CLI and CUD. We observed no robust association of CUD with AMI, CMI, procedures performed, frequency of amputation, costs, or total length of stay.ConclusionsCannabis use disorder was associated with a significantly higher incidence of admission for acute limb ischemia. CUD was not associated with an increased risk of critical limb ischemia following sensitivity analysis. Given CUD is often seen in younger, less co-morbid patients it provides an important target for intervention in this population.
| S-EPMC9163779 | biostudies-literature
Project description: Not available
| S-EPMC6594368 | biostudies-literature
Project description: Not available
| S-EPMC4802465 | biostudies-literature
Project description:Critical limb ischemia (CLI) represents the most advanced stage of peripheral arterial obstructive disease (PAOD) with a severe obstruction of the arteries which markedly reduces blood flow to the extremities and has progressed to the point of severe rest pain and/or even tissue loss. Recent therapeutic strategies have focused on restoring this balance in favor of tissue survival using exogenous molecular and cellular agents to promote regeneration of the vasculature. These are based on stimulation of angiogenesis by extracellular and cellular components. This review article carries out a systematic analysis of the most recent scientific literature on the application of stem cells in patients with CLI. The results obtained from the detailed analysis of the recent literature data have confirmed the beneficial role of cell therapy in reducing the rate of major amputations in patients with CLI and improving their quality of life.
| S-EPMC4537766 | biostudies-literature
Project description:Acute heart failure syndromes (AHFS) remain a major cause of morbidity and mortality, in part because the development of new therapies for these disorders has been marked by frequent failure and little success. The heterogeneity of current approaches to AHFS drug development, particularly with regard to end points, remains a major potential barrier to progress in the field. End points involving hemodynamic status, biomarkers, symptoms, hospital stay, end organ function, and mortality have all been employed either alone or in combination in recent randomized clinical trials in AHFS. In this review, we will discuss the various end point domains from both a clinical and a statistical perspective, summarize the wide variety of end points used in completed and ongoing AHFS studies, and suggest steps for greater standardization of end points across AHFS trials.
| S-EPMC3961583 | biostudies-other