Comparativecost-effectivenessanalyses of cardiacmagneticresonanceimaging versus invasive coronary angiography combined with fractional flow reserve testing to diagnose ischemia in coronary artery disease

Introduction: According to guidelines, patients with coronary artery disease (CAD) should undergo revascularization if myocardial ischemia is present. While coronary angiography (CXA) allows the morphological assessment of CAD, the fractional flow reserve (FFR) has proved to be a complementary invasive test to assess the functional significance of CAD, i.e. to detect ischemia. Perfusion Cardiac Magnetic Resonance (CMR) has turned out to be a robust non-invasive technique to assess myocardial ischemia. The objective: is to compare the cost-effectiveness ratio - defined as the costs per patient correctly diagnosed - of two algorithms used to diagnose hemodynamically significant CAD in relation to the pretest likelihood of CAD: 1) aCMRto assess ischemia before referring positive patients to CXA (CMR + CXA), 2) a CXA in all patients combined with a FFR test in patients with angiographically positive stenoses (CXA + FFR). Methods: The costs, evaluated from the health care system perspective in the Swiss, German, the United Kingdom (UK) and the United States (US) contexts, included public prices of the different tests considered as outpatient procedures, complications' costs and costs induced by diagnosis errors (false negative). The effectiveness criterion wasthe ability to accurately identify apatient with significantCAD.Test performancesused in the model were based on the clinical literature. Using a mathematical model, we compared the cost-effectiveness ratio for both algorithms for hypothetical patient cohorts with different pretest likelihood of CAD. Results: The cost-effectiveness ratio decreased hyperbolically with increasing pretest likelihood of CAD for both strategies. CMR + CXA and CXA + FFR were equally costeffective at a pretest likelihood of CAD of 62% in Switzerland, 67% in Germany, 83% in the UK and 84% in the US with costs of CHF 5'794, Euros 1'472, £ 2'685 and $ 2'126 per patient correctly diagnosed. Below these thresholds, CMR + CXA showed lower costs per patient correctly diagnosed than CXA + FFR. Implications for the health care system/professionals/patients/society These results facilitate decision making for the clinical use of new generations of imaging procedures to detect ischemia. They show to what extent the cost-effectiveness to diagnose CAD depends on the prevalence of the disease.

Early detection of idiopathic Parkinson's disease based on magnetic resonance imaging

The diagnosis of idiopathic Parkinson's disease (IPD) is entirely clinical. The fact that neuronal damage begins 5-10 years before occurrence of sub-clinical signs, underlines the importance of preclinical diagnosis. A new approach for in-vivo pathophysiological assessment of IPD-related neurodegeneration was implemented based on recently developed neuroimaging methods. It is based on non- invasive magnetic resonance data sensitive to brain tissue property changes that precede macroscopic atrophy in the early stages of IPD. This research aims to determine the brain tissue property changes induced by neurodegeneration that can be linked to clinical phenotypes which will allow us to create a predictive model for early diagnosis in IPD. We hypothesized that the degree of disease progression in IPD patients will have a differential and specific impact on brain tissue properties used to create a predictive model of motor and non-motor impairment in IPD. We studied the potential of in-vivo quantitative imaging sensitive to neurodegeneration- related brain tissue characteristics to detect changes in patients with IPD. We carried out methodological work within the well established SPM8 framework to estimate the sensitivity of tissue probability maps for automated tissue classification for detection of early IPD. We performed whole-brain multi parameter mapping at high resolution followed by voxel-based morphometric (VBM) analysis and voxel-based quantification (VBQ) comparing healthy subjects to IPD patients. We found a trend demonstrating non-significant tissue property changes in the olfactory bulb area using the MT and R1 parameter with p<0.001. Comparing to the IPD patients, the healthy group presented a bilateral higher MT and R1 intensity in this specific functional region. These results did not correlate with age, severity or duration of disease. We failed to demonstrate any changes with the R2* parameter. We interpreted our findings as demyelination of the olfactory tract, which is clinically represented as anosmia. However, the lack of correlation with duration or severity complicates its implications in the creation of a predictive model of impairment in IPD.

Diagnostic de la maladie coronarienne stable par FFR non invasive, mythe ou réalité [Diagnosis of stable coronary artery disease with non-invasive FFR: myth or reality?].

Decision to revascularize a patient with stable coronary artery disease should be based on the detection of myocardial ischemia. If this decision can be straightforward with significant stenosis or in non-significant stenosis, the decision with intermediate stenosis is far more difficult and require invasive measures of functional impact of coronary stenosis on maximal blood (flow fractional flow reserve=FFR). A recent computer based method has been developed and is able to measure FFR with data acquired during a standard coronary CT-scan (FFRcT). Two recent clinical studies (DeFACTO and DISCOVER-FLOW) show that diagnostic performance of FFRcT was associated with improved diagnostic accuracy versus standard coronary CT-scan for the detection of myocardial ischemia although FFRcT need further development.

Non-invasive detection of coronary endothelial response to sequential handgrip exercise in coronary artery disease patients and healthy adults.

OBJECTIVES: Our objective is to test the hypothesis that coronary endothelial function (CorEndoFx) does not change with repeated isometric handgrip (IHG) stress in CAD patients or healthy subjects. BACKGROUND: Coronary responses to endothelial-dependent stressors are important measures of vascular risk that can change in response to environmental stimuli or pharmacologic interventions. The evaluation of the effect of an acute intervention on endothelial response is only valid if the measurement does not change significantly in the short term under normal conditions. Using 3.0 Tesla (T) MRI, we non-invasively compared two coronary artery endothelial function measurements separated by a ten minute interval in healthy subjects and patients with coronary artery disease (CAD). METHODS: Twenty healthy adult subjects and 12 CAD patients were studied on a commercial 3.0 T whole-body MR imaging system. Coronary cross-sectional area (CSA), peak diastolic coronary flow velocity (PDFV) and blood-flow were quantified before and during continuous IHG stress, an endothelial-dependent stressor. The IHG exercise with imaging was repeated after a 10 minute recovery period. RESULTS: In healthy adults, coronary artery CSA changes and blood-flow increases did not differ between the first and second stresses (mean % change ±SEM, first vs. second stress CSA: 14.8%±3.3% vs. 17.8%±3.6%, p = 0.24; PDFV: 27.5%±4.9% vs. 24.2%±4.5%, p = 0.54; blood-flow: 44.3%±8.3 vs. 44.8%±8.1, p = 0.84). The coronary vasoreactive responses in the CAD patients also did not differ between the first and second stresses (mean % change ±SEM, first stress vs. second stress: CSA: -6.4%±2.0% vs. -5.0%±2.4%, p = 0.22; PDFV: -4.0%±4.6% vs. -4.2%±5.3%, p = 0.83; blood-flow: -9.7%±5.1% vs. -8.7%±6.3%, p = 0.38). CONCLUSION: MRI measures of CorEndoFx are unchanged during repeated isometric handgrip exercise tests in CAD patients and healthy adults. These findings demonstrate the repeatability of noninvasive 3T MRI assessment of CorEndoFx and support its use in future studies designed to determine the effects of acute interventions on coronary vasoreactivity.

Invasive candidiasis: comparison of management choices by infectious disease and critical care specialists.

OBJECTIVE: To compare the management of invasive candidiasis between infectious disease and critical care specialists. DESIGN AND SETTING: Clinical case scenarios of invasive candidiasis were presented during interactive sessions at national specialty meetings. Participants responded to questions using an anonymous electronic voting system. PATIENTS AND PARTICIPANTS: Sixty-five infectious disease and 51 critical care physicians in Switzerland. RESULTS: Critical care specialists were more likely to ask advice from a colleague with expertise in the field of fungal infections to treat Candida glabrata (19.5% vs. 3.5%) and C. krusei (36.4% vs. 3.3%) candidemia. Most participants reported that they would change or remove a central venous catheter in the presence of candidemia, but 77.1% of critical care specialists would start concomitant antifungal treatment, compared to only 50% of infectious disease specialists. Similarly, more critical care specialists would start antifungal prophylaxis when Candida spp. are isolated from the peritoneal fluid at time of surgery for peritonitis resulting from bowel perforation (22.2% vs. 7.2%). The two groups equally considered Candida spp. as pathogens in tertiary peritonitis, but critical care specialists would more frequently use amphotericin B than fluconazole, caspofungin, or voriconazole. In mechanically ventilated patients the isolation of 10(4) Candida spp. from a bronchoalveolar lavage was considered a colonizing organism by 94.9% of infectious disease, compared to 46.8% of critical care specialists, with a marked difference in the use of antifungal agents (5.1% vs. 51%). CONCLUSIONS: These data highlight differences between management approaches for candidiasis in two groups of specialists, particularly in the reported use of antifungals.

On the Selection of Non-Invasive Methods Based on Speech Analysis Oriented to Automatic Alzheimer Disease Diagnosis

The work presented here is part of a larger study to identify novel technologies and biomarkers for early Alzheimer disease (AD) detection and it focuses on evaluating the suitability of a new approach for early AD diagnosis by non-invasive methods. The purpose is to examine in a pilot study the potential of applying intelligent algorithms to speech features obtained from suspected patients in order to contribute to the improvement of diagnosis of AD and its degree of severity. In this sense, Artificial Neural Networks (ANN) have been used for the automatic classification of the two classes (AD and control subjects). Two human issues have been analyzed for feature selection: Spontaneous Speech and Emotional Response. Not only linear features but also non-linear ones, such as Fractal Dimension, have been explored. The approach is non invasive, low cost and without any side effects. Obtained experimental results were very satisfactory and promising for early diagnosis and classification of AD patients.

Role of meprins to protect ileal mucosa of Crohn's disease patients from colonization by adherent-invasive E. coli

Ileal lesions in Crohn's disease (CD) patients are colonized by pathogenic adherent-invasive Escherichia coli (AIEC) able to adhere to and invade intestinal epithelial cells (IEC), and to survive within macrophages. The interaction of AIEC with IEC depends on bacterial factors mainly type 1 pili, flagella, and outer membrane proteins. In humans, proteases can act as host defence mechanisms to counteract bacterial colonization. The protease meprin, composed of multimeric complexes of the two subunits alpha and beta, is abundantly expressed in IECs. Decreased levels of this protease correlate with the severity of the inflammation in patients with inflammatory bowel disease. The aim of the present study was to analyze the ability of meprin to modulate the interaction of AIEC with IECs. In patients with ileal CD we observed decreased levels of meprins, in particular that of meprin β. Dose-dependent inhibition of the abilities of AIEC strain LF82 to adhere to and invade intestinal epithelial T84 cells was observed when bacteria were pre-treated with both exogenous meprin α and meprin β. Dose-dependent proteolytic degradation of type 1 pili was observed in the presence of active meprins, but not with heat-inactivated meprins, and pretreatment of AIEC bacteria with meprins impaired their ability to bind mannosylated host receptors and led to decreased secretion of the pro-inflammatory cytokine IL-8 by infected T84 cells. Thus, decreased levels of protective meprins as observed in CD patients may contribute to increased AIEC colonization.

Invasive findings in patients with angina equivalent symptoms but no coronary artery disease; Results from the heart quest cohort study

The cause of angina in patients presenting at coronary angiography without significant coronary artery disease (CAD) has not been systematically assessed in a large prospective cohort. This study is aimed to identify the cause of angina in these patients.

Non-invasive gene-expression-based detection of well-developed collateral function in individuals with and without coronary artery disease

BACKGROUND: In patients with coronary artery disease (CAD), a well grown collateral circulation has been shown to be important. The aim of this prospective study using peripheral blood monocytes was to identify marker genes for an extensively grown coronary collateral circulation. METHODS: Collateral flow index (CFI) was obtained invasively by angioplasty pressure sensor guidewire in 160 individuals (110 patients with CAD, and 50 individuals without CAD). RNA was extracted from monocytes followed by microarray-based gene-expression analysis. 76 selected genes were analysed by real-time polymerase chain reaction (PCR). A receiver operating characteristics analysis based on differential gene expression was then performed to separate individuals with poor (CFI<0.21) and well-developed collaterals (CFI>or=0.21) Thereafter, the influence of the chemokine MCP-1 on the expression of six selected genes was tested by PCR. RESULTS: The expression of 203 genes significantly correlated with CFI (p = 0.000002-0.00267) in patients with CAD and 56 genes in individuals without CAD (p = 00079-0.0430). Biological pathway analysis revealed 76 of those genes belonging to four different pathways: angiogenesis, integrin-, platelet-derived growth factor-, and transforming growth factor beta-signalling. Three genes in each subgroup differentiated with high specificity among individuals with low and high CFI (>or=0.21). Two out of these genes showed pronounced differential expression between the two groups after cell stimulation with MCP-1. CONCLUSIONS: Genetic factors play a role in the formation and the preformation of the coronary collateral circulation. Gene expression analysis in peripheral blood monocytes can be used for non-invasive differentiation between individuals with poorly and with well grown collaterals. MCP-1 can influence the arteriogenic potential of monocytes.

Non-invasive diagnosis of coronary artery disease using cardiogoniometry performed at rest

PRINCIPLES: Cardiogoniometry is a non-invasive technique for quantitative three-dimensional vectorial analysis of myocardial depolarization and repolarization. We describe a method of surface electrophysiological cardiac assessment using cardiogoniometry performed at rest to detect variables helpful in identifying coronary artery disease. METHODS: Cardiogoniometry was performed in 793 patients prior to diagnostic coronary angiography. Using 13 variables in men and 10 in women, values from 461 patients were retrospectively analyzed to obtain a diagnostic score that would identify patients having coronary artery disease. This score was then prospectively validated on 332 patients. RESULTS: Cardiogoniometry showed a prospective diagnostic sensitivity of 64%, and a specificity of 82%. ECG diagnostic sensitivity was significantly lower, with 53% and a similar specificity of 75%. CONCLUSIONS: Cardiogoniometry is a new, noninvasive, quantitative electrodiagnostic technique which is helpful in identifying patients with coronary artery disease. It can easily be performed at rest and delivers an accurate, automated diagnostic score.

Stable coronary artery disease: revascularisation and invasive strategies

Stable coronary artery disease is the most common clinical manifestation of ischaemic heart disease and a leading cause of mortality worldwide. Myocardial revascularisation is a mainstay in the treatment of symptomatic patients or those with ischaemia-producing coronary lesions, and reduces ischaemia to a greater extent than medical treatment. Documentation of ischaemia and plaque burden is fundamental in the risk stratification of patients with stable coronary artery disease, and several invasive and non-invasive techniques are available (eg, fractional flow reserve or intravascular ultrasound) or being validated (eg, instantaneous wave-free ratio and optical coherence tomography). The use of new-generation drug-eluting stents and arterial conduits greatly improve clinical outcome in patients undergoing percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG). PCI is feasible, safe, and effective in many patients with stable coronary artery disease who remain symptomatic despite medical treatment. In patients with multivessel and left main coronary artery disease, the decision between PCI or CABG is guided by the local Heart Team (team of different cardiovascular specialists, including non-invasive and invasive cardiologists, and cardiac surgeons), who carefully judge the possible benefits and risks inherent to PCI and CABG. In specific subsets, such as patients with diabetes and advanced, multivessel coronary artery disease, CABG remains the standard of care in view of improved protection against recurrent ischaemic adverse events.

Use of pneumococcal vaccine in people with chronic disease in United States

Objective. The risk of complications and deaths related to pneumococcal infections is high among high risk population (i.e. those with chronic diseases such as diabetes or asthma), despite current immunization recommendations. The aim of this study is to evaluate the use of pneumonia vaccine in adults with and without diabetes or asthma by year of age and whether immunization practices conform to policy recommendations. ^ Methods. Data were drawn from 2005 Behavioral Risk Factor Surveillance Study. Age specific estimated counts and proportions of pneumonia vaccination status were computed. The association of socio-demographic factors with vaccination status was estimated from multiple logistic regression and results were presented for adults (18-64yrs) and elderly (65 or older). ^ Results. Overall 12.3% of the adults and 61.5% of elderly reported ever received pneumonia vaccine. 66.8% of diabetics and 72.6% of asthmatics received the vaccine among elderly. 33.4% of diabetics and 21.6% of asthmatics received the vaccine among adults. These numbers are far away from Healthy people 2010 objective coverage rates of 90% for elderly and 60% for high risk adults. Though diabetes was one of the recommendations for the pneumonia vaccine still the status was less than 70% even at older ages. Although asthma was not an indication for pneumonia vaccine, asthmatics still achieved 50% level by an early age of 60 and reached up to 80% at as early as 75 years. In those having both asthma and diabetes, although the curve reaches to 50% level at a very early age of 40yrs, it is not stable until the age of 55 and percentages reached to as high as 90% in older ages. Odds of receiving pneumonia vaccine were high in individuals with diabetes or asthma in both the age groups. But the odds were stronger for diabetics in adults compared to those in the elderly [2.24 CI (2.08-2.42) and 1.32 CI (1.18-1.47)]. The odds were slightly higher in adults than in elderly for asthmatics [1.92 CI (1.80-2.04) and 1.73 CI (1.50-2.00)].The likelihood of vaccination also differed by gender, ethnicity, marital status, income category, having a health insurance, current employment, physician visit in last year, reporting of good to excellent health and flu vaccine status. ^ Conclusion. There is a very high proportion of high risk adults and elderly that remain unvaccinated. Given the proven efficacy and safety of vaccine there is a need for interventions targeting the barriers for under-vaccination with more emphasis on physician knowledge and practice as well as the recipient attitudes.^

Genes for the majority of group A streptococcal virulence factors and extracellular surface proteins do not confer an increased propensity to cause invasive disease

Background. The factors behind the reemergence of severe, invasive group A streptococcal (GAS) diseases are unclear, but it could be caused by altered genetic endowment in these organisms. However, data from previous studies assessing the association between single genetic factors and invasive disease are often conflicting, suggesting that other, as-yet unidentified factors are necessary for the development of this class of disease. Methods. In this study, we used a targeted GAS virulence microarray containing 226 GAS genes to determine the virulence gene repertoires of 68 GAS isolates (42 associated with invasive disease and 28 associated with noninvasive disease) collected in a defined geographic location during a contiguous time period. We then employed 3 advanced machine learning methods (genetic algorithm neural network, support vector machines, and classification trees) to identify genes with an increased association with invasive disease. Results. Virulence gene profiles of individual GAS isolates varied extensively among these geographically and temporally related strains. Using genetic algorithm neural network analysis, we identified 3 genes with a marginal overrepresentation in invasive disease isolates. Significantly, 2 of these genes, ssa and mf4, encoded superantigens but were only present in a restricted set of GAS M-types. The third gene, spa, was found in variable distributions in all M-types in the study. Conclusions. Our comprehensive analysis of GAS virulence profiles provides strong evidence for the incongruent relationships among any of the 226 genes represented on the array and the overall propensity of GAS to cause invasive disease, underscoring the pathogenic complexity of these diseases, as well as the importance of multiple bacteria and/ or host factors.