Cost-effectiveness of an insertable cardiac monitor in a high-risk population in the UK

Objective To evaluate the cost-effectiveness of insertable cardiac monitors (ICMs) compared with standard of care (SoC) for detecting atrial fibrillation (AF) in patients at high risk of stroke (CHADS 2 >2), using a UK National Health Service (NHS) perspective. Methods Using patient characteristics and clinical data from the REVEAL AF trial, a Markov model assessed the cost-effectiveness of detecting AF with an ICM compared with SoC. Costs and benefits were extrapolated across modelled patient lifetime. Ischaemic and haemorrhagic strokes, intracranial and extracranial haemorrhages and minor bleeds were modelled. Diagnostic and device costs were included, plus costs of treating stroke and bleeding events and costs of oral anticoagulants (OACs). Costs and health outcomes, measured as quality-adjusted life years (QALYs), were discounted at 3.5% per annum. One-way deterministic and probabilistic sensitivity analyses (PSA) were undertaken. Results The total per-patient cost for ICM was £13 360 versus £11 936 for SoC (namely, annual 24 hours Holter monitoring). ICMs generated a total of 6.50 QALYs versus 6.30 for SoC. The incremental cost-effectiveness ratio (ICER) was £7140/QALY gained, below the £20 000/QALY acceptability threshold. ICMs were cost-effective in 77.4% of PSA simulations. The number of ICMs needed to prevent one stroke was 21 and to cause a major bleed was 37. ICERs were sensitive to assumed proportions of patients initiating or discontinuing OAC after AF diagnosis, type of OAC used and how intense the traditional monitoring was assumed to be under SoC. Conclusions The use of ICMs to identify AF in a high-risk population is cost-effective for the UK NHS

Clinical outcome following acute ischaemic stroke relates to both activation and autoregulatory inhibition of cytokine production

BACKGROUND: As critical mediators of local and systemic inflammatory responses, cytokines are produced in the brain following ischaemic stroke. Some have been detected in the circulation of stroke patients, but their role and source is unclear. Focusing primarily on interleukin(IL)-1-related mechanisms, we serially measured plasma inflammatory markers, and the production of cytokines by whole blood, from 36 patients recruited within 12 h and followed up to 1 year after acute ischaemic stroke (AIS). RESULTS: Admission plasma IL-1 receptor antagonist (IL-1ra) concentration was elevated, relative to age-, sex-, and atherosclerosis-matched controls. IL-1β, soluble IL-1 receptor type II, tumour necrosis factor (TNF)-α, TNF-RII, IL-10 and leptin concentrations did not significantly differ from controls, but peak soluble TNF receptor type I (sTNF-RI) in the first week correlated strongly with computed tomography infarct volume at 5–7 days, mRS and BI at 3 and 12 months. Neopterin was raised in patients at 5–7 d, relative to controls, and in subjects with significant atherosclerosis. Spontaneous IL-1β, TNF-α and IL-6 gene and protein expression by blood cells was minimal, and induction of these cytokines by lipopolysaccharide (LPS) was significantly lower in patients than in controls during the first week. Minimum LPS-induced cytokine production correlated strongly with mRS and BI, and also with plasma cortisol. CONCLUSION: Absence of spontaneous whole blood gene activation or cytokine production suggests that peripheral blood cells are not the source of cytokines measured in plasma after AIS. Increased plasma IL-1ra within 12 h of AIS onset, the relationship between sTNF-RI and stroke severity, and suppressed cytokine induction suggests early activation of endogenous immunosuppressive mechanisms after AIS

Genes Involved in Systemic and Arterial Bed Dependent Atherosclerosis - Tampere Vascular Study

BACKGROUND: Atherosclerosis is a complex disease with hundreds of genes influencing its progression. In addition, the phenotype of the disease varies significantly depending on the arterial bed. METHODOLOGY/PRINCIPAL FINDINGS: We characterized the genes generally involved in human advanced atherosclerotic (AHA type V-VI) plaques in carotid and femoral arteries as well as aortas from 24 subjects of Tampere Vascular study and compared the results to non-atherosclerotic internal thoracic arteries (n=6) using genome-wide expression array and QRT-PCR. In addition we determined genes that were typical for each arterial plaque studied. To gain a comprehensive insight into the pathologic processes in the plaques we also analyzed pathways and gene sets dysregulated in this disease using gene set enrichment analysis (GSEA). According to the selection criteria used (>3.0 fold change and p-value <0.05), 235 genes were up-regulated and 68 genes down-regulated in the carotid plaques, 242 genes up-regulated and 116 down-regulated in the femoral plaques and 256 genes up-regulated and 49 genes down-regulated in the aortic plaques. Nine genes were found to be specifically induced predominantly in aortic plaques, e.g., lactoferrin, and three genes in femoral plaques, e.g., chondroadherin, whereas no gene was found to be specific for carotid plaques. In pathway analysis, a total of 28 pathways or gene sets were found to be significantly dysregulated in atherosclerotic plaques (false discovery rate [FDR] <0.25). CONCLUSIONS: This study describes comprehensively the gene expression changes that generally prevail in human atherosclerotic plaques. In addition, site specific genes induced only in femoral or aortic plaques were found, reflecting that atherosclerotic process has unique features in different vascular beds

Italian guidelines for primary headaches: 2012 revised version

The first edition of the Italian diagnostic and therapeutic guidelines for primary headaches in adults was published in J Headache Pain 2(Suppl. 1):105–190 (2001). Ten years later, the guideline committee of the Italian Society for the Study of Headaches (SISC) decided it was time to update therapeutic guidelines. A literature search was carried out on Medline database, and all articles on primary headache treatments in English, German, French and Italian published from February 2001 to December 2011 were taken into account. Only randomized controlled trials (RCT) and meta-analyses were analysed for each drug. If RCT were lacking, open studies and case series were also examined. According to the previous edition, four levels of recommendation were defined on the basis of levels of evidence, scientific strength of evidence and clinical effectiveness. Recommendations for symptomatic and prophylactic treatment of migraine and cluster headache were therefore revised with respect to previous 2001 guidelines and a section was dedicated to non-pharmacological treatment. This article reports a summary of the revised version published in extenso in an Italian version